KIDNEYDISEASE

KIDNEY—DISEASE–

AGuideforLiving

WALTERA.HUNT

ForewordbyRonaldD.Perrone,M.D.TuftsMedicalCenter

NOTESTOTHEREADER.Thisbookisnotmeanttosubstituteformedicalcareofpeoplewithkidneydisease,andtreatmentshouldnotbebasedsolelyonitscontents.Instead,treatmentmustbedevelopedinadialoguebetweentheindividualandhisorherphysician.Ourbookhasbeenwrittentohelpwiththatdialogue.

Theauthorandpublisherhavemadereasonableeffortstodeterminethattheselectionanddosageofdrugsdiscussedinthistextconformtothepracticesofthegeneralmedicalcommunity.ThemedicationsdescribeddonotnecessarilyhavespecificapprovalbytheU.S.FoodandDrugAdministrationforuseinthediseasesanddosagesforwhichtheyarerecommended.Inviewofongoingresearch,changesingovernmentalregulations,andtheconstantflowofinformationrelatingtodrugtherapyanddrugreactions,thereaderisurgedtocheckthepackageinsertofeachdrugforanychangeinindicationsanddosageandforwarningsandprecautions.Thisisparticularlyimportantwhentherecommendedagentisanewand/orinfrequentlyuseddrug.

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Includesbibliographicalreferencesandindex.ISBN-13:978-0-8018-9963-8(hardcover:alk.paper)ISBN-10:0-8018-9963-X(hardcover:alk.paper)ISBN-13:978-0-80189964-5(pbk.:alk.paper)ISBN-10:0-8018-9964-8(pbk.:alk.paper)

1.Kidneys—Diseases—Popularworks.2.Kidneys—Diseases—Treatment—

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CONTENTS

Foreword,byRonaldD.Perrone,M.D.Preface

Chapter1UNDERSTANDINGKIDNEYFAILURE

Chapter2WHATKIDNEYSDO

Chapter3WHYKIDNEYSFAIL

Chapter4DIAGNOSINGANDMANAGINGKIDNEYDISEASE

Chapter5PREVENTINGANDPOSTPONINGKIDNEYFAILURE

Chapter6DIALYSIS

Chapter7TRANSPLANTATION

Chapter8FUTURETREATMENTOPTIONS

EPILOGUE

NotesGlossaryResourcesIndex

FOREWORD

Itisapleasuretowritethisforeword.Veryfewbookslikethisoneareavailableforpeoplediagnosedwithkidneydisease.Medicalinformationaboutkidneydiseaseandkidneyfailureisabundant,yetimportantperspectivesfrompatientswhohaveactuallyexperiencedkidneydisease,kidneyfailure,andresultingdialysisandtransplantationarenoteasilyobtained.WalterHunthasprovidedcarefulandunderstandableexplanationsforthelayperson,andhe’sofferedhispersonalexperiencewithandperspectivesonhowkidneyfailurehasaffectedhislife.Icongratulatehimforprovidingthisexcellentguideforpeoplewithkidneydisease.

Imadethedecisiontoenterthefieldofnephrologyduringmysecondyearofmedicalschoolwhiledoingarotationontheinpatientnephrologyservice.Witnessingthemiracleoftransplantationandthelife-savingtreatmentofdialysisencouragedmebecauseIrecognizedthat,asaphysician,Iwouldhavethesetoolstohelppatientsovercomeseriousillness.Beforethesetreatmentsbecameavailable,kidneyfailurewasadiseasewithverylimitedtherapeuticoptions.

Workingwithpeoplenewlydiagnosedwithkidneydiseaseandwithpeoplewhohavebeenlivingwithkidneydiseaseforalongtimeprovidestremendousopportunitiestoinfluencetheircare.WhenImeetnewlydiagnosedpeople,myhopeforthemis,first,toprovideaspecificandaccuratediagnosis.Then,ifatreatmentisavailable,Iimplementtreatmenttoslowtheprogressofthedisease.Itisimportanttoeducatepatientsatthisstage,toinformthemandtheirfamiliesaboutthedisease,andtoenlistthefamily’sparticipationinthepatient’scare.Ifnecessary,Ibegintreatmenttopreventandmanagepotentialcomplicationsandprovidereassuranceabouttheoptionsfortherapy,includingdialysisandtransplantation.Allofthisisnoteasilyaccomplishedduringasinglevisit!Therelationshipbetweenpatientanddoctorisalong-termonewithmultipleopportunitiesformypatientstoaskquestionsandtoreceiveinformationfromprintorelectronicsourcestohelpthemunderstandandmanagetheirdisease.

Follow-upvisitsprovidepatientsandmeadditionalopportunitiestogoovertheircare,todiscusshowtheyaredoingfortheirpartofthecare,andtosolidifythebondofcomfortandtrustthatoccurswithalong-termdoctor-patientrelationship.AtthesevisitsIoftenhaveanotheropportunitytointeractwithadditionalfamilymembersaswell.Differentstagesofthediseaserequire

additionalfamilymembersaswell.Differentstagesofthediseaserequiredifferentinterventions.Longperiodsofstabilityaregratifyingforeveryoneinvolvedanddon’tnecessarilyrequirelongdiscussionsoranyintervention;incontrast,theapproachofend-stagerenalfailureandtheneedfordialysisortransplantcanprovokemuchanxietyandrequirefrequentvisitsforeducation,counseling,andmedicationadjustment.

Receivingadiagnosisofkidneydiseaseisfrighteningfornearlyeveryone.Vividfearsofdialysisandrapidprogressiontokidneyfailurearecommon.Moreoftenthannot,thereareinterventionstoslowtheprogressionofchronickidneydiseaseandtomanagethecomplications.Althoughtheseinterventionsarenotcures—inthewaythatanantibioticcancurepneumonia—theycanbehelpfulinpreservinghealth.

Ibelieveitisimportantforindividualswithkidneydiseasetobefullyengagedinthemanagementoftheirdisease.Whenpatientsareengagedandinvolved,it’smorelikelythattheprogressionofthediseasewillbeslowedandcomplicationswillbeprevented.Therearemultipleopportunitiesforpatientstoimprovetheirlong-termoutcome.Theycanbecomeeducatedaboutthedisease,takeappropriatemedicationandmanagetheirdiet,obtainahomebloodpressuredeviceandregularlymeasureandreportbloodpressure,joinpatientsupportgroups,andsupportresearchandeducationaleffortsbyfoundationsliketheNationalKidneyFoundationandthePolycysticKidneyDiseaseFoundation.

Dialysisisnotaperfecttreatmentforkidneyfailure,but,nonetheless,itislifesavingandcanprovideareasonablequalityoflifeforindividuals.Improvementsindialysistechnologyandtheincreasingavailabilityofhomedialysisanddailydialysistreatmentshaveledtomuchbetteroutcomesformanyindividuals.Transplantation,whilenotacureforkidneydisease,isanexcellenttreatment,yetitstillrequiresfrequentvisitstomedicalproviders,lotsofpills,andpotentiallyseriouscomplicationsfromthesepotentmedications.Greatlyimprovedqualityoflifeandlongerliferesultfromthisintervention,butcarefulcomplianceandfollow-uparenecessary.

Asaphysicianwhohasnotpersonallyexperiencedkidneydisease,myunderstandingoftheterrifyingnatureofreceivingadiagnosisofkidneydiseasehasalwayscometomesecondhand.InKidneyDisease:AGuideforLiving,WalterHuntprovidesanhonestperspectiveofsomeonewhohasexperiencedlossofkidneyfunction,hadyearsofdialysis,andreceivedasuccessfultransplant.Theseinsightsandpersonalexperiences,alongwithexplanationsofbiologyandmedicaltreatment,areatremendousresource.Thereassuranceprovidedbysomeone“whohasbeenthere”will,Ihope,decreasetheanxietyfor

thosewhoarenewlydiagnosedorarefacingnewtreatmentslikedialysisortransplantation.

Itismyhopethatyouwillusethisbookforguidanceandcompanionshipasyoujourneythroughthecomplexitiesofthediagnosisandtreatmentofchronickidneydisease.

RonaldD.Perrone,M.D.AssociateChief,DivisionofNephrology

TuftsMedicalCenter

PREFACE

Nearly550,000peopleintheUnitedStatessufferfromchronickidneyfailureandrequiredialysisortransplantationtolive.Iamoneofthem.Iinheritedageneticdefectthatcausedcyststoforminmykidneys,eventuallydestroyingmykidneyfunction.FortenyearsIdealtwithkidneyfailure,includingmorethansevenyearsondialysisandnumerouscomplications,beforereceivingasuccessfulkidneytransplant.Calledpolycystickidneydisease(PKD),thegeneticdefectIhaveisthefourthleadingcauseofkidneyfailureintheUnitedStates.PeoplewithPKDhavea50percentchanceofinheritingitfromanaffectedparent.MymotherandsisterhadPKDandultimatelydiedfromcomplicationsofthedisease.

WhenIfirstrealizedthatmykidneysmightfail,Isearchedforresourcesthatwouldhelpmeprepareforwhatwastocome.Plentyofinformationwasavailabledescribingkidneydiseaseandthewaysdoctorstreatkidneyfailure.However,Icouldnotfindasystematicdiscussionofwhatitwouldbeliketoexperiencekidneyfailureanditstreatment.Mydoctorswerenotabletohelpmeimaginewhattheexperiencewouldbelike.Althoughadoctorcanbeempatheticwheninteractingwithpatients,unlesshehaspersonallyexperiencedkidneyfailure,adoctor’sperspectiveofkidneyfailureislargelyamedicalone,notapersonalone.

Idecidedtowritethisbooktoprovideaserviceforotherpeoplelikeme,peoplewantingpracticalinformationaboutwhatcauseskidneyfailure,howpatientscanhelpthemselvescopebothphysicallyandemotionally,andwhatfactorscanhelpthemmakepersonalhealthcaredecisions.Informationhelpspeoplemakebetterdecisions,potentiallyleadingtobetteroutcomes,andhelpsthemfeelmoreincontroloftheircondition—bothofwhichprovideabetterqualityoflife.AlthoughIamnotaphysician,mythirty-yearcareerinmedicalresearchhelpsmeunderstandthesciencebehindkidneyfailureandthetreatmentsavailable.Also,overtheyearsIhavelearnedhowtocopewithmanyoftheproblemsofkidneyfailure.Itismysincerehopethatthisbookwillassistyouincomingtotermswithyourownuniquesituation.

Afterfirstcoveringthebasicsofhowkidneysfunction(chapters1and2),whykidneyscanfail(chapter3),thediagnosisandmanagementofkidneyfailure(chapter4),andstrategiestoreducekidneydeterioration(chapter5),I

discussthetwotreatmentoptionsforkidneyfailure:dialysis(chapter6)andtransplantation(chapter7).Inchapter8,Idescribepromisingtreatmentsthatarebeingdevelopedandthatonedaymaychangethecourseofkidneydisease.ThroughoutthebookIincludecitationstootherpublicationsthatyoumaywishtoconsultforfurtherdiscussionofspecifictopics.Alistofresourcesappearsattheendofthebook.Becausethemeaningofsomeofthescientifictermsmaybedifficulttorememberfromchaptertochapter,aglossaryisincludedthatdefineskeywords.

ThroughoutthebookIdiscussmypersonaltreatmentdecisions.Whenconsideringdialysis,didIwanttocontrolmytreatmentonmyownscheduleathome,orhavesomeoneelsedoitformeatadialysiscenter,ontheirschedule?Inthecaseoftransplantation,wasIwillingtocompromisemyimmunesystemfortherestofmylifeandriskdevelopinginfectionsandevencancerinexchangeforabetterqualityoflife?Ultimately,Ihadtodecideformyself.Youwill,too.Idiscusstheprosandconsofeachtreatment,basedonmyownexperienceandscientificresearch,tohelpyoudecide,withyourdoctor,whatisbestforyou.

WhenIpresentscientificinformationrelatedtokidneydisease,Ihavetriedtowriteinawaythatmakesthisinformationunderstandabletoeveryone,includingpeoplewithnoscientifictraining.It’sworthrepeatingthateducatingyourselfaboutyourdiseasecanmakeabigdifferenceinpreparingyourselfforyourfuturetreatment.Realizingthatyouhavetherightandtheabilitytochoosewillbeamajorassetinhavingasayinyourmedicaltreatment.Ifyouaregroundedinsufficientknowledgetoknowwhatquestionstoask,youwillbeinabetterpositiontocontributetoyourtreatment.Havingchoices,evenwhentheyarenotalwaysgoodones,isempowering.Thisbookwillputyouinabetterpositiontomakemoreinformedchoices.

Icouldnothavecompletedthisbookwithoutthesupportandadviceofthemanypeoplewhoreaddraftsofthemanuscript,includingDr.BobCraig,BobbieFesta,NancyHayes,LindaHowerton,JuliaRoberts,Dr.BernieRabin,andHowardJung,Jr.Inaddition,IwouldliketothankJillMcMasterandDr.Y.NabilYakubforreviewingearlyversionsofthebook.

SpecialthanksareowedtoDr.RonaldPerrone.Ronsharedmanyhoursofhistimeexplainingkidneyfailurefromadoctor’sperspectiveandmakingsurethattheinformationinthisbookisaccurate.Hedidsowithgoodcheerandclear

explanations.Anyinaccuraciesthatmayhavecreptinafterhisthoroughreviewsaremysoleresponsibility.IgreatlyappreciateRon’stime,scholarship,andcollegialspiritinbringingthisbooktofruition.

Finally,IwishtothanktheJohnsHopkinsUniversityPressforsupportingthisproject,especiallymyeditor,JacquelineWehmueller.Herskill,support,andadvicewereindispensableincreatingthefinalwork.Itwasgreatworkingwithher.

KIDNEYDISEASE

1UNDERSTANDINGKIDNEYFAILURE

OnAugust11,1997,acatheterwasimplantedinmyabdomensoIcouldreceivedialysis.Mykidneyshadfailed.Icouldstillurinate,butIcouldn’teliminateallthewasteproductsthatIaccumulatedfromfood.It’snaturaltotakeurinatingforgranted—it’ssomethingwe’vedonesincethedaywewereborn!Asadultswethinkaboutgoingtothebathroomonlywhenwecan’tgettoonebecausewe’retrappedinabusinessmeeting,say,orstuckintraffic.Andwedonotusuallydiscussurinationinpolitecompany.Whenweneedtourinate,wejustexcuseourselvesoradoptaeuphemism—we’regoingtothepowderroomorwe’regoingtoseeamanaboutahorse.

Whenurinatingisnolongeranormal,almosttrivial,activity,ourlivesarealtered.Whenurinatingbecomesafocusofourattention,ourlivesareradicallychanged.Whenmykidneysstartedtoshutdown,Ifoundtheprospectofkidneyfailureoverwhelming.Ihadsomanyquestions:“Whyaremykidneysfailing?IsthereanythingIcandotosavemykidneys?HowwillIknowwhenmykidneyshavefailed?Whatwillitfeellikewhenmykidneysfail?Isthereacureortreatmentforkidneyfailure?”

Thegoodnews,asIfoundout,isthatkidneyfailureisnolongeradeathsentence,asitoncewas.Thoseofuswithkidneyfailurecanstillhaveproductivelives.Thebadnewsisthatwemayspendcountlesshoursgoingtodialysisanddoctors’officesandmakingsurewetakeallourmedications.Therearesomeaspectsofthediseasethatwecan’tcontrol.Oneaspectofthediseasethatwecancontrolishowwellweunderstandit.Understandingkidneyfailure—whatcausesit,howitmayaffectourlives,andwhatoptionswehave—canhelpustakeanactiveroleintreatingourdisease,liftourspirits,achieveabetteroutcome,andimproveourqualityoflife.

HowManyPeopleHaveIt?ThenumberofpeoplewithchronickidneyfailureintheUnitedStatesisrisingatanalarmingrate.Manyofthepeoplebeingnewlydiagnosedaredevelopingkidneyfailureasaconsequenceofuncontrolleddiabetes.The2010AnnualDataReportissuedbytheNationalInstitutesofHealthindicatesthatbytheendof2008,nearly550,000peopleintheUnitedStateswerebeingtreatedforchronic

kidneyfailureorend-stagerenaldisease(ESRD).1Thatsameyear,doctorsdiagnosedmorethan112,000newcasesofchronickidneyfailure.

Theprimarycausesofkidneyfailurearediabetes,hypertension,glomerulardiseases,andpolycystickidneydisease(PKD).Intable1.1,youcanseethenumberofpeopleafflictedwiththesefourdiseaseswhoalsohavekidneyfailure.Figure1.1showsthepercentageofallpeoplewithkidneyfailurethatcanbeattributedtoeachcause(calledprevalence)duringthesameperiod.Figure1.2illustrateshowthepictureischanging,withmorenewcasesbeingattributedtodiabetes.

Table1.1KidneyFailureintheUnitedStates,2008

Diabetesandhypertensionaccountfor62percentofthecasesofkidneyfailure.Therestofthecasesresultfromglomerulardiseases,polycystickidneydisease,andothercausesnotreflectedinfigure1.1.Alarmingly,thenewcasesattributedtodiabetesandhypertensionjumpedto72percentduring2008(figure1.2).Diabetes,themostcommoncauseofkidneyfailure,accountsfor44percentofnewcasesofkidneyfailure.Becauseobesitycanleadtodiabetesandbecauseanincreasingnumberofpeopleareobeseormorbidlyobese,morepeopleareatriskofkidneyfailure.Theincidenceofnewcasesofkidneydiseaseduetodiabetesisalmost50,000eachyear(slightlylowerthanin2007).Ontheotherhand,newcasesofglomerulardiseasesdeclinedtolessthan7,500.

Figure1.1.CausesofKidneyFailure,2008

Figure1.2.NewCasesofKidneyFailure,byCauseofKidneyFailure,2008

Inanerawhenhealthcarecostsarebeingscrutinized,it’sworthmentioningthatin2007thecostoftreatingpeoplewithkidneyfailureintheUnitedStateswasmorethan$26.8billionperyearinMedicarespending.

DiseaseandEmotions

Discoveringthatwehaveachronic,potentiallyfataldiseasecanbeoverwhelming.Itseemsthatlifeasweknowithaschanged,perhapsforever.Sometimesthisistrue,whenwehaveadiseasethatdoctorscanonlymanage,nottreatorcure.Althoughpeoplewithkidneyfailurerequiresomeformofinterventionfortheirentirelives,doctorscanmanageandtreatkidneyfailure.

WhenIdiscoveredthatIhadaseriouschronicdisease,IexperiencedemotionalreactionssimilartothesixstagesofgriefrelatedtodeathasdescribedbyElisabethKübler-Ross:fear,denial,anger,bargaining,depression,and,finally,acceptance.2Lossofkidneyfunctionparallelssomeaspectsofdeath.Kidneyfailurecanrepresentthelossoflifeasweknowit.Ourreactionsmightbejustascompellingasthoseofpeopleapproachingdeath,sincewearenotsureifwewillsurvive.Myemotionalreactionsdidnotnecessarilyrepresentacontinuumofresponses.Theycameandwentoverthecourseofmydisease.EvenwhenIfinallyacceptedmydisease,Ioccasionallybecameangryanddepressedaboutmycondition.Attimes,Iwasjusttired.However,ifIwantedtolive,whichIdid,Ihadtocometotermswithalltheaspectsofkidneyfailure.

Nearlyeveryonewhohasachronicdiseaseexperiencesfearanddenial.Notknowingwhattodocanbeterrifyingandparalyzing.Wemayknowlittleaboutourconditionandmaybeafraidofsufferingorevendying.Sometimeswemaynotwanttobelievethatwehaveaseriousillness.Peoplewhohavespentactivelivesfinditdifficulttoaccepttherestrictionsplacedonmanyactivitiesthatarepartoflife.Itiseasiertoignoretheprobleminhopesthatthediagnosisiswrongorthattheillnesswilljustgoaway.

Yetdenialservesausefulpurposebyrationingonlytheamountofinformationandemotionwecanprocessatanygiventime.Profoundlossisdifficultforeventhestrongestpeople.Denialgivesustimetoabsorbthenewsofourillnessinameasuredway.Wecannotbelievethatourkidneysarefailing.Wefeelfine.Later,thesignificanceofwhatishappeningtousbecomesmoreofareality.

Oncewecannolongerdenythefactthatwehaveachronicillnessandthefullweightofitsrealitysinksin,weoftenbecomeangry.Whyme?WhatdidIdotodeservethis?CouldIhavedonesomethingtopreventmyillness?Thequestionsareendless.Youmightconcludeyouhavebeentargetedforillness,possiblyassomeformofpunishment.Thisisnottrue.Althoughcontractinganillnessisnotexactlyrandom—manyillnessesareinfluencedbygeneticandlifestylefactors—itisnotpersonal,either.Wecanimagineallkindsof“whatif”scenarios.Ifonlywehaddonesomethingdifferently,maybetheoutcomewould

havebeendifferent.Processingangercanbeanimportantpartofemotionalhealing.Feelingyourangercanhelpyoumoveon.

PeoplewhobelieveinGodmaytrybargainingforabetteroutcome.IfyoupromisetodedicatetheremainderofyourlifetoGod’spurpose,maybeGodwillgivebackyourkidneyfunction.Intheend,however,itdoesnotmatter.Thelossispermanent.Wehavetofacetherealityofourkidneyfailure.

Whentherealityoflosingkidneyfunctionfinallysetsin,theemotionalresponsescandeepen,possiblyleadingtodepression,eithersteadyorintermittent.Minordepression—feelingsad—isnormalifitdoesnotbecometoosevere.Likedenial,depressioncanallowthebraintimetoabsorbthefullimpactofthediagnosis.Eventually,afterdepressionhasserveditspurpose,itcandissipate.Butmoreseveredepressioncanmakeyourtreatmentmoredifficult,robbingyouofthemotivationandenergyyouneedtogettreatmentandtakecareofyourself.Depressionthatdoesnotsubsideisaveryseriousconditionthatmayrequiremedicalattention.

Onceyouhavemovedthroughthestagesoffear,denial,anger,bargaining,anddepression,youmaybegintoacceptyourdiagnosis.Intime,youwillrealizethatyoucannolongeravoidkidneydisease.Itisatthispointthatyouhavethegreatestopportunitytotakecontrolofyourhealth,evenifitmeansyourlifewillneverbethesameagain.

EducatingYourself—andOtherToolsforDealingwithKidneyFailure

Noteveryonegetsawarningthattheirkidneysareindangeroffailing.Somepeoplediscoverthattheyhavehadhighbloodpressureforalongtimewithoutknowingit.Forotherpeople,kidneysfailbecauseofdiabetesorothercausesthatcouldpossiblyhavebeenprevented.

Inmyowncase,Ilivedfortwentyyearsknowingmykidneysmightfail,butIseldomthoughtaboutitseriously.BecausemymotherandsisterhaddiedofcomplicationsofPKDIknewImighthavethedisease,butIdidnotexperiencesymptoms,otherthanhighbloodpressure,untilIwasalmost45yearsold.ThatwasthefirsttimeIhadtoconfrontmyownmortality,anditterrifiedme.Eventually,IhadtoacceptmyfatewhetherIwantedtoornot.Acceptanceissomethingthatnearlyeveryonewithkidneydiseasecanachieve.

Likepeoplewithotherchronicdiseases,peoplewithkidneydiseasemustmanagetheirdiseaseeverydayfortherestoftheirlives.Therearenodaysoff,andnovacations.Ifwedonottreatourfailingkidneys,wecanbecomesickerandpossiblydie.However,oncewelearnwhattodoandintegratethoselessons

andpossiblydie.However,oncewelearnwhattodoandintegratethoselessonsintoourlives,ourlivescanbecomemorenormal.Lifewillnotbethesameaswhenwewerewell,butwecanstillpursueahappyone.Itmaynotseemthatwayatthispoint,butduringthecourseofthisbook,Ihopetoconvinceyouthatyourlifeisnotoverwithkidneyfailure,andthatotheropportunitiesarepossible.Iwillshowyouhow.

First,learneverythingyoucanaboutyourdisease.Youmaynothaveamedicalbackground,butyoushouldbeabletograspthebasicsofyourdiseasewhentheyaredescribedinlanguageyouunderstand.Thisbookwillintroduceyoutoinformationthatwillallowyoutohavemorecontroloveryourcondition.IfoundthatthemoreIunderstoodaboutkidneyfailure,thelessafraidIfelt.

Therearemanysourcesofinformationaboutkidneydisease.Startwithyourdoctor.Severalkidneydiseaseorganizationsprovideinformationinaccessiblelanguage.Formoretechnicalinformation,accessthemedicalliteraturethroughtheLibraryofMedicineattheNationalInstitutesofHealthinBethesda,Maryland.(AdditionaldetailsaboutsuchorganizationsandwaystoaccessthemedicalliteratureareprovidedintheResourcessectionattheendofthisbook.)

AsIlearnedmoreaboutmydisease,IfoundthatIhadfarlesstobeconcernedaboutthanIthought.Therewouldbetoughtimes,butIknewthatwiththeknowledgethatIacquiredandwiththerightattitude,Icouldmaketheprocessoftreatmentmucheasier.Asatrainedscientist,IwasabletoexaminethescientificliteraturetolearnaboutmydiseaseandIwasabletounderstandwhatwashappeningtome.Butmanyscholarlyarticlesaretootechnicalforthenon-technicallytrainedperson.OnethingIneverfoundwasacompletediscussionofkidneyfailurefromapatient’spointofview.Thisbookaimstofillthisvoid.

IrealizedearlyintheprogressionofmydiseasethatIwasultimatelyresponsibleformyhealthandrecovery.Ifeltthatmydoctorsweremyadvisors,andthatIwasresponsibleforfollowingtheirdirectionsandforthedecisionsthatweultimatelymade.IfIdidnotagreewithadoctororwasunsureofwhattodo,IconsultedwithotherdoctorsuntilIwasconvincedthatacourseofactionwasrightforme.Realizingthatyoualwayshaveoptionstochoosefrom,evenifsomeofthemareunattractive,givesyougreatpower.

BeforeIstarteddialysis,mydoctorhadmecompleteaformoutliningseveraldialysistreatmentoptions.Inadditiontothetwotypesofdialysis,theformgavemethechoiceofdecliningdialysis.DecliningdialysiswouldhavemeantthatIwoulddie.Instead,Ichosetolive.

Havingchoicesgivesyoucontrol.Oneoftheworstaspectsofhavinga

Havingchoicesgivesyoucontrol.Oneoftheworstaspectsofhavingachronicdiseaseisfeelinghelplessandnotknowingwhattodo.Controlcanseemlikemerelytellingpeoplewhattodo.However,itisnotthatsimple.Beingincontrolcomesfromhavingknowledgeofyourconditionandbeingabletoarticulateyourviewsandposequestionstoyourdoctorsandothersfromacalm,informedperspective.Gettingtothepointoffeelingincontrolcantaketime.Keepinganopenmindtothepossibilitiesofrecoverycanhelpyoumaintainapositiveattitudetowardyourdisease.

Onceourkidneysfail,wehaveonlytwotreatmentchoices:dialysis(eitherperitonealdialysisorhemodialysis)ortransplantation.Amajorissueforpeoplewithkidneyfailureisdecidingwhichformoftreatmentisbest.Oftenwewilljustacceptwhatourdoctorstelluswithoutthinkingmuchabouthowthetreatmentwillchangeourlives.Iwassurprisedathowlittledoctorsknewabouttheday-to-dayaspectsoflivingwiththetreatmentstheyprescribed.Forme,itwasimportanttomakeupmyownmindandfeelthatIhadcontroloverwhathappenedtome.Ifoundthatfeelingincontrol(orevenhavingtheillusionofcontrol)wasthemosthelpfulfactorinfacingkidneyfailure.Feelingincontrolmayhelpyouwithyourchronicillness.

Inaddition,researchershavediscoverednumerousways,includingusingmedicationsandfollowingnutritionalguidelines,eithertopreventyourkidneysfromfailingortoreducetherateoftheirdeterioration.Evenifyourkidneyseventuallyfail,thereareapproachestomakingyourlifeeasierandmoreproductive.

CopingSkillsWhentherealityofkidneyfailuresetin,Iwasfrightenedanddidn’tknowwhattodo.OverthedecadeduringwhichmykidneyswerefailingandattheendofwhichIreceivedasuccessfultransplant,Ilearnedhowtomanagemydisease.Sometimesitwasn’teasy.Generalinformationaboutkidneyfailureandtreatmentoptionswasavailable,butinformationabouthowtodecidewhichoptionstopursueandhowtoadapttothemwerenot.Frommyexperience,IwillsharesomeconsiderationsIhadwithmydiseasethatIhopewillhelpyouwithyourownexperience.First,herearesomegeneralcopingskillsIlearnedthathelpedme.Theymayhelpyou,too.

MoveQuicklythroughDenialandFaceYourDiseaseDirectly

Iexperiencedalltheemotionalreactionstoloss,describedearlier,tovaryingdegrees,butfinallyrealizedthatIwasultimatelyresponsibleformyhealth.IhadtoacceptthatIwassick.AlthoughthethoughtwasunpleasantandIwanted

hadtoacceptthatIwassick.AlthoughthethoughtwasunpleasantandIwantedtohidefromit,inthefinalanalysis,Iwasbetteroffconfrontingmydisease.NoonewouldbemoremotivatedthanIwouldbetogetwellandliveaswellasIcould.Inasense,Ifeltempoweredbyacceptingmydisease.

BeYourOwnAdvocate

Inadditiontoeducatingmyselfaboutmydiseasetoreducefear,Ifounditimportanttousemyknowledgetohelpmydoctorsgivemethebestcarepossible.Doctorscannotreadminds.Theyoftenrelyonfeedbackfromtheirpatientsabouthowtheyfeelandaboutreactionstotreatmentsthattheyprescribe.Ifyoudonottellyourdoctorsaboutyourreactionstotheirtreatments,theywillhaveamoredifficultjobintreatingyou.Furthermore,doctorsshouldunderstandhowthesetreatmentsaffectyourlife.Afterall,youhavetolivewiththem.Donotbeafraidtoaskquestionsorchallengeatreatmentoptionifyouthinkyoucannothandleit.Ifyouaretoosicktobeyourownadvocate,findsomeonewhocandothatforyou.Itcanbeafamilymemberorfriend.Myfriendshelpedmewhenmyconditionwasveryserious.

Doctorsdotheirbesttobeawareofthelatesttreatmentsavailableforyou.However,somenewapproachmaycomealongthatyoumightwanttopursue.Discussitwithyourdoctortodetermineifitmightbebeneficialforyou.Besatisfiedthatyouarereceivingthebestandmosteffectivetreatmentforyourdisease.

EmbraceYourInnerStrength

Wehavedifferentpersonalitiesandtemperaments.Ononeextreme,somepeoplefeelweakandpowerless,sensingthattheyhavelittlecontrolovertheirlives.Mostly,theydependonothersforsupportandfeelthattheycannotlivewithoutthehelpofothers.Attheotherextreme,somepeoplefeelintotalcontrolandindependent.Theycantakeontheworldanddothingswithhelpfromrelativelyfewpeople.Mostofusfallbetweenthesetwoextremes.

Whenadversitystrikes,eventhestrongestofuscanquestionourselvesanddoubtourabilitytoconqueroursituation.Theweakestcanfeelevenmorehelplessandhopeless.Iwasinthemiddle.Iwentthroughmanyself-doubtswhenIknewmykidneyswouldfail.However,IdiscoveredintimethatIhadareserveofinnerstrengththatIhadnotappreciated.Tosurvivepsychologically,Ihadtofindthatinnerstrength.IamnotsurehowIfoundit,butIthinkitcamefromastrongdesiretosurvive.OnceIknewIhadthisinnerstrengthandrealizedIneededtoimprovemysituationandconquermydiseaselargelyalone,Iembracedmystrength.You,too,candoit.Ihavenosecretformula,butyou

willfindit,ifyouallowyourselftolookforyourinnerstrengthanduseittohelpyouthroughthedifficulttimes.Somepeopleturntoreligiontofindthestrength,whereasothersdiscoveritintheirabilitytosolvetheirownproblems.Nomatterhowyoudoit,Ihavelearnedthatfindingandembracingyourinnerstrengthisworththejourney.

BelieveYourLifeWillImprove

Havingachronicdisease,especiallykidneydisease,doesnotnecessarilymeanthatyourlifeisover.Itisamazinghowpeoplewiththemostdebilitatingdiseasesorinjuriesoftengoontohavefulfillinglives.Take,forexample,thelateChristopherReeve,theactorwhobecamequadriplegicafterfallingfromahorse,breakinghisneck,andseveringhisspinalcord.Despitehisgraveinjuries,Reevefirmlybelievedthathewouldwalkagain.Hefacedhisdifficultcircumstanceswithcourage,dignity,andpassion,andhebecameaneffectiveadvocateforincreasingresearchfundingtotreatspinalcordinjuries.Althoughheultimatelydiedfromcomplicationsrelatedtohisinjury,whilehelivedReevesignificantlyraisedawarenessofspinalcordinjuryandhelpedincreaseresearchfunding—accomplishmentsthatmusthavebeenverygratifyingtohim.

Inmyowncase,whatkeptmegoingwasthebeliefthatintheend,Iwouldreceiveatransplantandmylifewouldbebetter.Iwasdiscouragedfromtimetotime,butIdidnotlosesightofthegoalofreceivinganewkidney.IevenbeganplanningactivitiesIwantedtopursue,liketravelingandflyingairplanes.

TaketheLongView

Themindhasawayofblurringmemoriesthelongertimegoesby.MymemoriesofnastyhospitalstaysormajorsurgeriesfadedonceIreceivedmykidneytransplant.Thus,whenIconfrontedwhatappearedtobeadifficultsituation,Ilookedaheadtothepointwhenmymemorywouldbefuzzy.Ibelievedeverythingwouldeventuallybeokay.Whenfriendsofminefacesurgeryorothertraumaticevents,Ikeepremindingthemthatinsixmonths,theiremotionalresponseswillbeconsiderablylessintensethantheyareatthepresent.

RemainOptimisticandGiveaPositiveSpintoEverything

Oftenthereweretimeswhenmysituationseemedbleak.Onafewoccasions,therewasthepossibilitythatImightnotsurvive.IfounditextremelyimportanttobelievethatIwouldgetbetter.AlthoughnospecificcurewasavailableforPKD,IknewthatIcouldbetreatedsuccessfullyforkidneyfailure.WhetherIremainedondialysisorreceivedatransplant,IbelievedthatIcouldcreateafulfillinglife.Regardlessofwhathappenedtome,Ialwaystriedtolookatmy

fulfillinglife.Regardlessofwhathappenedtome,Ialwaystriedtolookatmysituationwithoptimism.Thismademyrecoverymucheasier.

KnowYourPrioritiesandSticktoThem

Asakidneydialysispatient,Iwascontinuallyfatigued,whichlimitedmyparticipationinmanyoftheactivitiesIenjoyed.ConsideringthecompetingdemandsthatIconfrontedeveryday,IknewthatIcouldnotrespondtoeverything.Instead,Idevelopedalistofprioritiesthatwereimportanttome.Myhealthwasatthetopofthelist.Withoutmyhealth,noneoftheotherprioritiesmattered.HavingprioritieshelpedmedecidewhatIcoulddoorwhatIcouldnotdo.Itwasveryimportantformetolearntheword“no.”Ifarequestwasnotconsistentwithmypriorities,Ididnotfeelobligedtoaccept.

BeWillingtoTakeRisks

Doctorsarenotalwayssurewhytheirpatientsaresick.Theycanrunamultitudeofmedicaltests,andthecauseoftheillnessstillmaynotbeclear.ThathappenedtomewhenIdevelopedanumberofseriousinfectionsin1999.Atthetime,Iwasondialysis.Duringmymanyvisitstothehospital,mydoctorsperformedalltypesofprocedurestolocatethesourceofinfection,buttonoavail.ManypatientswithPKDhavekidneyinfections,andmedicaltestsmayshowsomeobjectivediagnosticmeasurestoverifyadiagnosisofkidneyinfection.Forexample,bloodorurineculturesmighthavefoundevidenceforbacteria.However,noneofmyculturesdid.

Basedontheirexperience,severalnephrologistsrecommendedthatIhavemykidneysremoved.Iwasnotparticularlycrazyaboutsuchaprospect,becauseIwasstillpassingafairamountofurineforapersonwithkidneyfailure,andhavingmykidneysremovedwaslife-threatening,majorsurgery.However,Icouldnotreceiveatransplantwithanactiveinfectionoronesuppressedbyantibiotics.Ontheotherhand,Icouldhavemykidneysremovedandstillhavetheinfections.Ididnotwanttoplacemyselfatsuchriskfornothing.Itwasnotasurething.ButbecauseIwantedatransplant,IfeltthatIhadtotaketheriskandhadbothkidneysremoved.Fortunately,everythingworkedoutalright.Theinfectionsdisappearedafterthesurgeonremovedmykidneys,andoverthesucceedingmonths,Ifeltprogressivelybetter.Theriskultimatelywasworthit.

AskforHelp,ButDon’tDependonIt

WhenIwasverysickIcouldnotdosomethingsonmyown,likedrivingorshopping.Mostofthetime,IhadfriendswhocouldhelpmewhenIneededit.However,theywerenotalwaysavailable,especiallyonshortnotice.Ifoundthat

itwasimportanttohavebackupplans,likeusingtaxisorcountyservicesfortransportationorevenahomeworkerifneeded.Keepinmindthatcare-givershavelivesandresponsibilitiesoftheirownandmaynothaveendlesstimeandenergytodevotetoyou.IfoundthatifIworkedtobeindependent,evenwhenIfeltatmyworst,Iavoidedfeelinghelpless.

KeepYourSenseofHumor

Someoneoncesaidthatlaughteristhebestmedicine.Ifoundthattobetrueinmycaseaswell.Findingthehumorinlife’schallengescanbefreeing.Forexample,manyofusinmydialysiscenterengagedinourownformofblackhumor.InaFrankensteiniansortofway,wewouldpokefunatallthetubesandgadgetsthatattachedustodialysismachines.Somepeoplenotfamiliarwithdialysisdidnotunderstandthehumororwereuncomfortablewithit.That’sokay—evenbeyondillness,lifeprovidesplentyofthingstolaughabout.

Ourkidneysareinvolvedinmanyoftheamazingprocessesthathelpourbodiesfunction.Inthefollowingchapterwe’lltakeacloserlookatthekidneysandhowtheywork.

2WHATKIDNEYSDO

Thekidneyisanexceptionallysophisticatedandefficientpurificationsystemthatcleansesthebloodofunwantedbyproductsproducedbythebody.(Thesebyproductsarecalledmetabolites.)Althoughwehavetwokidneys,weneedonlyonekidneytolive.Infact,peoplecanlosemostoftheirkidneyfunctionwithoutbecomingill.

Mostorgansinthebodycontrolonlyonefunction.Theheartpumpsblood,andthestomachdigestsfood.Butkidneysnotonlyfilterblood,theyalsoregulateanumberofotherbodyfunctions:

•Balancingtheamountofwaterandsalts(calledelectrolytes)retainedbythebody

•Controllingbloodpressure•Maintainingtheproperbalanceofacidityintheblood•Regulatingtheproductionofredbloodcells(callederythrocytes)thatcarryoxygentothevariousorgansofthebody

•Controllingthelevelofphosphateintheblood•ActivatingvitaminD

Thekidneysfunctiontokeepconditionsinthebodywithinanormalrange,knownashomeostasis.Allofthesefunctionscanbeaffectedwhenkidneysfail.

FiltrationHumansarenottheonlyanimalswithkidneys.Allvertebrates(animalsthathaveaspine)havekidneys.Theearliestvertebrateslivedinwater.Becausefishtakealotofwaterintotheirbodies,theyneedamechanismtoeliminateexcessamounts.Saltwaterfishalsorequireameanstoeliminateexcesssaltthattheyabsorb.Ifsaltwaterfishcouldnotexpelexcesswaterandsaltfromtheirbodies,theywouldblowuplikeaballoonandeventuallyexplode.Kidneysmayhaveevolvedinanimalstoregulatewaterandsaltbalance.

Kidneysinvertebrateslikeusalsoeliminatewasteproducts.Wasteproducts

areproducedwhenwedigestproteins(likethosefoundinmeat,fish,ordairyproducts).Carbohydrates(sugarsandstarches)areeventuallybrokendown(metabolized)intowaterandcarbondioxide.However,whenglucose(orsugar)exceedsacertainlevelintheblood,thekidneybeginseliminatingtheexcess.Whenaperson’sbodyexpelssugarintheurine,itcanbeasignthatthepersonhasdiabetes(seechapter3).

Kidneysarethebody’ssimplefiltrationsystem.Asimplesystemforfilteringliquidsremovesparticlesthataregreaterthanacertainsize,whethertheybecoffeegroundsormicrobes.Filtersusuallyhavefourparts:(1)areservoirintowhichtheliquidpasses,likeafunnel;(2)thefilteritself,likeporouspaper,membranes,orcheesecloth;(3)thefunnelstem,likeahoseorstraw;and(4)acollectionreceptacle,likeabottleorjar.Weusefilterseverydaywhenwepercolatecoffeeorpurifytapwater.Mostfiltrationsystemsusepaperoractivatedcharcoalasfilters.Kidneysareabitmorecomplicated,buttheirfiltrationsystemworksinasimilarway.

Thekidneyisbean-shaped,approximatelythesizeofanadult’sfist,andweighsabouthalfapound.Likeasimplefiltrationsystem,thekidneyhasfourbasicparts.Lookingatfigure2.1,whichcomparesthekidneyswithafunnel,weseethatbloodcontainingwastesfirstentersthekidneyfromabranchoftherenalartery,whichislikethereservoirofthefunnel.Thebloodpassesthroughthefiltrationapparatus,calledthenephron.Eachkidneycontainsaboutonemillionnephrons.Nephronsarecomposedoftheglomerulus,thetubularsystem,andthecollectingduct.

Thefirstpartofthenephronistheglomerulus(thefilter),whichhasalargesurfaceareatoprovideefficientfiltration.Thelargerorthickerthefilter,themoreefficientlyittrapsbiggerparticles.Theglomerulusallowssmallmoleculestopassthroughitwhileretaininglargesubstancesthatthebodyneeds,likevariousbloodcellsandproteinmolecules,andeliminateswasteproductsthebodydoesnotneed.Inthekidney,filtrationoccursasthebloodisforcedthroughthewallsoftheglomerulusandnumeroussmallvessels,throughwhichbloodcellscannotpass,intothetubularsystem(thestemofthefunnel).Filtrationproducesaplasma-likefluidcalledfiltrate.Substancesthatthebodystillneedspassthroughtheglomerulus.

Thefiltrateleavestheglomerulusandentersthetubulesandcollectingducts,wheretheusefulsubstancesarereabsorbed.Unlikethehollowstemofasimplefunnel,tubulesandcollectingductsarehighlycomplex,withspecializedstructuresthatremovewasteproductswhilereabsorbingnutrientsandsaltsthatthebodyneeds.Whatisleftisurine.Thecollectingductconnectedtothe

thebodyneeds.Whatisleftisurine.Thecollectingductconnectedtothebladder(thecollectionreceptacle,akintothecoffeepot)providesthefinalfiltrationstepforurinebeforethebodyeliminatesit.

Figure2.1.TheFunnelingPropertiesoftheKidney

Let’stakeacloserlookatthetubularsystem.Asweseeinfigure2.1,thetubulesattachtotheglomerulusandloopthroughthekidney.Tubuleseliminateurea,themainbyproductofproteinbreakdownfromthebody.However,thebodyneedssomeofthesalts,water,andothernutrientsthatalsopassfromthebloodthroughthekidney’sfilter(glomerulus)intothefiltrate.Thetubulesatvariouspointsontheloopsprocessthefiltratefurthertoreabsorbintothecapillariesthesalts,water,andnutrientsthebodyneedsbackintotheblood.Anyexcesssaltsandwaternotneededbythebodyremaininthefiltratetobe

eliminatedasurine.So,theentireprocessoffiltrationthattakesplaceinthekidneysinvolvesfilteringandreabsorbing—untileverythingusefulhasbeenreabsorbedandeverythingelseissenttothebladdertobeeliminatedfromthebodyasurine.

RegulatingBloodPressureInadditiontofiltering,kidneyshelpkeepbloodpressurefromdroppingtoolow.Theydosobymakingandreleasinganenzymecalledrenin.Maintainingbloodpressurewithrenininvolvesseveralorgansinthebody,includingtheliver,lungs,andadrenalglands(seefigure2.2).

Reninpreventsthebodyfromdevelopingdangerouslylowsodium(salt)concentrations,leadingtolowbloodpressure.Suchaconditioncanoccurinhotweather,whenthebodysweatsprofusely,orwithsubstantialbloodloss.Topreventlowbloodpressureduringsaltdepletion,thekidneyreleasesreninintothebloodstream.Whenreninreachestheliver,itreactswithaproteincalledangiotensinogentoproduceabiologicallyinactiveproteincalledangiotensinI.

Figure2.2.HowReninRegulatesBloodPressure

WhenangiotensinIleavestheliver,ittravelstothelungs,whereitisconvertedintheveinstoangiotensinII.Whiletravelingthroughthebody,angiotensinIIconstrictsbloodvesselsandraisesbloodpressure.Inaddition,angiotensinIIactsontheadrenalglands,twosmallendocrineglands,onelocatedontopofeachkidney.Intheadrenalgland,angiotensinIIstimulatesthereleaseofthehormonecalledaldosterone,whichcandirectthekidneystoretainsodiumandwater.It’seasytoseehowtheoverproductionofrenincancontributetohighbloodpressure(seechapter3).

RegulatingBloodAcidityThebodymaintainstheblood’snarrowrangeofaciditywithbuffers.Thebufferingprocessisregulatedpredominantlybyabalancebetweencarbonicacid

andbicarbonate(bakingsoda)inthebloodandbytheacidityoftheurine.Inthekidney,acidalongthetubularmembraneswapsplaceswithsodium(oneofthesalts)andbicarbonate.Variousconditionscanchangetheacidityoftheblood.Ifyoubreathetoohardandtoofast,thebloodcanbecomelessacidicbecauseofareductionofcarbondioxide.Ifthekidneydoesnotfunctionproperly,acidcanaccumulate,aconditionknownasacidosis.

ProducingRedBloodCellsBonemarrowmakesredbloodcells(erythrocytes)thatcarryoxygenthroughoutthebody.Redbloodcellsliveaboutfourmonthsandthenmustbereplaced.Thekidneysproduceahormonecallederythropoietin,whichcontrolstherateatwhichredbloodcellsform.Whenthekidneysensestoolittleoxygenintheblood,itreleaseserythropoietintostimulatethebonemarrowtomakemoreredbloodcells.Whenkidneyfunctionisdegradedorlostandthekidneysmakeinsufficienterythropoietin,patientsmayhavetoofewredbloodcells,aconditioncalledanemia.

RegulatingPhosphatePhosphateisessentialforthebodytoproduceenergy.Dairyproductsareamajorsourceofphosphate.Numerouschemicalreactionsinthebodyusephosphate,butourdietsgenerallyprovidemorephosphatethanweneed.Thekidneyistheonlymeansofeliminatingexcessphosphatecarriedintheblood.Ifthekidneymalfunctions,severalproblemscanresultfromanexcessofphosphate.

Phosphatereadilycombineswithcalcium.Whenexcessphosphatebindstoenoughcalcium,thebodythinksitdoesnothaveenoughcalciumintheblood,promptingbonestoreleasecalciumintothebloodstream.Whencalciumisreleasedintothebloodstream,peoplemaydeveloposteoporosisandformcalciumphosphateplaquesintheirorgans,possiblyleadingtoorganfailure(seechapter4).

RegulatingBoneStructureExcessphosphateinthebloodisnottheonlycauseofbonedemineralization.VitaminD,afat-solublevitamin,playsanimportantroleinthebody’sabsorptionofcalciumtomaintainstrongbonesandteeth.MakingvitaminDisacomplicatedprocessinvolvingactiveandlessactiveformsofvitaminD(seefigure2.3).

Figure2.3.HowVitaminDIsProduced

ThebodymakesactiveformsofvitaminDfromcholesterol.Onewayisfromsunlight:ultravioletlightstimulatestheformationofcholecalciferol,aderivativeofcholesterol,intheskin.ActivatedcholecalciferolthenpassesthroughtheliverandbecomesanevenmoreactiveformofvitaminDcalledcalcidiol.ThefinalactivationofvitaminDoccursinthekidney.Whencalcidiolentersthekidney,itisconvertedtocalcitriol,theonlyformofvitaminDthatthebodyactuallyuses.Somedietarysupplementscontaincholecalciferol,bypassingtheneedforthesun’sactivationoflessactiveformsofvitaminD.Failingkidneysmayaffectthebody’sabilitytoabsorbvitaminD,whichcanleadtoboneloss.

Manyofthebody’sessentialactivitiesdependonnormalkidneyfunction.Whenkidneysfail,therearemajorconsequencesforthebody.Inthefollowingchapterwediscusswhykidneysmayfail.

3WHYKIDNEYSFAIL

Numeroushealthproblemscanleadtokidneyfailure.Thefourmaincausesarediabetes,hypertension,glomerulardiseases,andpolycystickidneydisease(PKD).Geneticsplaysaroleinmostcausesofkidneyfailure,andkidneyfailuremayresultfromaspecificdefectinheritedfromoneorbothparents.PKDisprimarilyaninheritedkidneydisease.

Geneticsisnotthewholestory,however.Lifestyleandotherenvironmentalfactorsmayalsobesignificantinfluences.Thischapterbeginswithaprimeronthegeneticandenvironmentalfactorscontributingtokidneyfailure.Knowledgeofthesefactorswillhelpyouunderstandhowyoumightslowtheprogressionofyourdisease.

NatureversusNurtureGeneticFactors

Allofthefunctionsinourbodiesoperateonthebasisofinstructionsembeddedinourgeneticcode.Overthepastfiftyyears,researchershaveuncoveredtheintricatedetailsofhowthisgeneticcodeworks.TheHumanGenomeProject,whichwascompletedin2003,determinedthecompletenucleotidesequenceofhumandeoxyribonucleicacid(DNA).Genesprovideablueprintforcreatingourbodiesandmakingthemwork.Just

astheblueprintsforahouseshowhowtobuilditsvariousparts,likethefoundation,walls,androof,genesdirecttheconstructionofcells,organs,bone,andskin.Moreover,liketheheating,airconditioning,andelectricalsystemsthatcontroltheenvironmentalconditionsinahouse,genescontrolhowourbodiesfunction.

Theprimarypurposeofgenesismakingproteins.Proteinsarelikeabuilding’sconstructionworkersandengineers.Theymakeandoperatethehumanbodyaccordingtothegeneticblueprintsresidingwithinthechromosomes.

Forallorgansofthebody,ourgenesissuetheinstructions(orblueprints)tomakeproteinswhileweareinthewomb.Fororganstodevelopcorrectly,certainprocessesmusthappeninanexactway.Itstartswhenaspermfertilizestheegg.Thecellsintheresultingembryo,possessingtwocopiesofeachgene,

theegg.Thecellsintheresultingembryo,possessingtwocopiesofeachgene,onefromeachparent,begintodivide.Astheembryogrows,copiesofgenesinheritedfromeachparentmustbereproducedidenticallyineachnewcell,sothatallthecellsinthedevelopingfetus(andeventuallyintheperson’sbody)willhavethesamesetofgeneticblueprints.Duringaperson’slifetime,manyofthecellsinthebodywilldieandbereplacedwithnewones.Thesenewcellsgenerallyalsocontainthesameblueprints.

Althoughrare,mistakescanoccurwhengenesarecopied.Calledmutations,thesemistakescancausetheorganstoworkimproperly.Ifahouse’sblueprintsarewrong,adoormightbelocatedinthewrongplaceorthelightingsystemmightfailbecauseofincorrectwiring.Inpeople,genemistakesarepassedalongtotheirchildrenandcancausethemtoinheritadisease.Forexample,mutationsingenesthatmakeorcontrolkidneyscanmalfunction,leadingtodisease.

EnvironmentalFactors

Behavioralandenvironmentalfactorscanalsocontributetotheexpressionorprogressionofadisease.Inthecaseofkidneyfailure,animproperdietandlackofexerciseorotherlifestylefactorscancontributegreatlytoaperson’smedicalstatus.Wedonotdeliberatelysetouttomakeourselvesill.However,withthestressesofourcultureandeverydaylife,itcanbeeasytoneglectourownhealth.Betweenwork,family,andsocialobligations,wearesobusythatwemayhavelittletimetoeatproperlyortogetadequateexercise.Overtime,ourhealthcanbegintofailwithoutourevenknowingit.

Whenpeopledon’teatrightanddon’texercise,theyaremorelikelytobeoverweightorobese.ObesityhasreachedepidemicproportionsintheUnitedStatesandinotherdevelopedcountries.Accordingtoarecentstudy,66.3percentofAmericansareoverweight,obese,ormorbidlyobese.1AfricanAmericansandHispanicAmericanshaveahigherprevalenceofobesitythannon-Hispanicwhites.Moreover,womenacrossallracesaremoreobesethanmen.Obesityincreaseswithage,levelingoffbyage60ordecliningthereafter.

Obesitymayleadtootherhealthcomplications—includingkidneyfailure—becauseobesitymakespeoplemorelikelytodevelopdiabetesandhypertension.Excessweightcanalsocausecoronaryheartdisease,highcholesterollevels,andstroke,whichcanleadtodeath.

DiseasesThatCauseKidneyFailureReferencestothesymptomsofkidneydisordersbytheancientGreekssuggestthatwehaveknownaboutkidneyfailureforthousandsofyears.Weweren’tabletoanalyzekidneysandotherorgansuntilthenineteenthcentury,however.

abletoanalyzekidneysandotherorgansuntilthenineteenthcentury,however.In1827,theEnglishphysicianRichardBrightfirstdescribedthesymptomsofkidneyfailure.

Inthetwenty-firstcentury,kidneyfailureisstillincurable,butitcanbepreventedandtreated.Withdialysisandtransplantation,peoplewithkidneyfailurecancontinuetohaveproductivelives.Nevertheless,failingkidneystakeaveryhighmedical,emotional,andfinancialtoll.Thereisnocureforkidneyfailure,butknowingitscausescanhelpprevent,delay,orprepareforit.

Aswelearnedinchapter1,approximatelyone-halfmillionpeopleintheUnitedStatesarelivingwithkidneyfailure.Inmostcases,diabetesandhypertensionarethecauses.Botharepreventable(seechapter5).Glomerulardisorders,whichcanhavebothenvironmentalandgeneticorigins,areanothercauseofkidneyfailure.Therearealsoinheritedcausesofkidneyfailure,likePKD.Ifapersoninheritsmutatedgenes,thediseasewilldevelop,althoughtheprogressionofthediseasevariesamongfamiliesandindividuals.Thischapterpresentsabriefoverviewofeachofthesefourleadingcausesofkidneyfailure.

Diabetes

Diabetes(alsoknownasdiabetesmellitus)istheleadingcauseofkidneyfailureintheUnitedStatesandaccountsfor38percentofcases.Becauseofrisingobesityrates,diabetesratesareincreasing,evenamongchildren.Asmanyas20.6millionpeoplehavediabetes.Aspeopleage,theybecomemoresusceptibletodiabetes(seefigure3.1).Aboutone-halfofallpeoplewithdiabetesareover60yearsold.Acrossthepopulation,slightlymorementhanwomenhavediabetes,anditdisproportionatelyaffectsNativeAmericans,non-HispanicAfricanAmericans,andHispanicAmericans(seefigure3.2).Understandingtheunderlyingcausesofdiabetesisessentialforlearninghowtopreventandtreatit.

Figure3.1.EstimatedTotalPrevalenceofDiabetesinPeopleAged20YearsandOlder,byAgeGroup,UnitedStates,2005

Source:1999–2002NationalHealthandNutritionExaminationSurveyestimatesoftotalprevalence(bothdiagnosedandundiagnosedwereprojectedtoyear

2005).

Diabetesisametabolicdiseaseinwhichthebodydoesnotproperlyutilizeglucose.Glucoseisthemainsourceofenergyinthebody.Inorderforglucosetoentercellsandproduceenergy,thepancreassecretestheproteininsulinintothebloodstreamtohelpglucosecrossthemembranessurroundingcells.Ifthisprocessisinterrupted,glucoseaccumulatesinthebloodandcanspilloutintotheurine.Cellscanstarvewithoutglucose,evenwithhighconcentrationsofglucoseintheblood,ifitcannotpermeatecellmembranes.

Figure3.2.EstimatedAge-AdjustedTotalPrevalenceofDiabetesinPeopleAged20YearsandOlder,byRace/Ethnicity,UnitedStates,2005

Source:ForAmericanIndians/AlaskanNatives,theestimateoftotalprevalencewascalculatedusingtheestimateofdiagnoseddiabetesfromthe2003outpatientdatabaseoftheIndianHealthServiceandtheestimateofundiagnoseddiabetesfromthe1999–2002NationalHealthandNutritionExaminationSurvey.Forthe

othergroups,1999–2002NHANESestimatesoftotalprevalence(bothdiagnosedandundiagnosed)wereprojectedtoyear2005.

Theinabilityofinsulintoprocessglucoseefficientlycanoccurforoneoftworeasons:(1)alackofsufficientinsulinsecretionbythepancreasor(2)abody’sresistancetoinsulin,preventingthetransportofglucoseintothecells.Whenthepancreasdoesnotsecreteenoughinsulin,thisconditionisknownasType1diabetes.Attacksfromthebody’sownimmunesystemdestroybetacells,therebyreducinginsulinsecretion.PeoplewithType1diabetesmusttakeinsulintolive.Fiveto10percentofpeoplewithdiabeteshaveType1diabetes,whichusuallydevelopsinchildhood.Type1diabetesismoreprevalentinwhitesandrarelydevelopsinpeopleofotherraces.

ResearchershavefoundthatType1diabetesdevelopsbecauseofgeneticandenvironmentalfactors.Upto50percentofpeoplewithType1diabeteshavethediseasebecauseofgeneticsusceptibility—theyinheritedanincreasedlikelihoodofdevelopingit.Mutationsinanumberofgenesthatencodeproteinsinvolved

ofdevelopingit.Mutationsinanumberofgenesthatencodeproteinsinvolvedintheimmunesystemplayasignificantroleinthedevelopmentofdiabetes.Scientistsbelievethatenvironmentaltriggerslikeviralinfections,dietaryfactors,environmentaltoxins,psychologicalstress,andevenseasonoftheyearcanprecipitateType1diabetes.However,nosingletriggerappearsresponsible.

Type2diabetes,thenumberonecauseofkidneyfailure,accountsformostcasesofdiabetesandisclearlylinkedtoobesity.AccordingtotheNationalInstitutesofHealth,almost80percentofpeoplewithType2diabetesareoverweight.2InType2diabetes,althoughthepancreassecretesplentyofinsulin,thecellsofthebodybecomeresistanttoit,preventingthetransportofglucoseintothecells.LikepeoplewithType1diabetes,peoplewithType2diabetesalsomayneedinsulinsupplementationinordertolive.MildcasesofType2diabetescanbecontrolledthroughdietandoral,non-insulinmedications.

Type2diabetesismuchmoreprevalentinminoritypopulations,largelybecausethesegroupshavehigherratesofobesity.NativeAmericanshaveoneofthehighestratesofType2diabetesintheworld.OtherminoritygroupsgreatlyaffectedbyType2diabetesincludeAfricanAmericans,non-HispanicAfricanAmericans,andHispanicAmericans.Becauseofthehighratesofobesityinthesepopulations,theU.S.CentersforDiseaseControlandPreventionexpectstheratesofdiabetestoincreaseinthefuture.

Diabetescancreatemanycomplicationsaffectingalmosteverypartofthebody.Inadditiontokidneyfailure,diabetescanleadtoheartandbloodvesseldisease,strokes,blindness,limbamputations,andnervedamage.Babiesborntowomenwithuncontrolleddiabetescanhavebirthdefects.Thisisallabigpricetopayforadiseasethatispreventableinmostcasesbymaintaininganormalweight.Medicalresearchersareworkinghardtoidentifythehormonalandenvironmentalcausesofincreasingratesofobesity,andtodeveloptreatmentsandprogramstoconquertheobesityepidemic.(Seebelowformoreinformationabouthormonesandobesityandaboutobesityanddiabetes.)

Type2diabeteshasapoorlyunderstoodgeneticcomponent.Researchisunderwaytodeterminewhichgenesareinvolvedandtowhatextenttheyplayaroleinthedevelopmentofthedisease.Havinganswerstothesequestionswillhelpdoctorsidentifywhoismostsusceptibletodiabetesandlocatepotentialtargetsfortreatment.

Type2diabetesrunsinfamilies.However,thegeneticbasisofthemutationsthatleadtodiabetesvariesamongfamilymembers.Thus,anumberofdifferentgenesmayberesponsibleforanincreasedsusceptibilitytoType2diabetes.

Althoughresearchershavestudiedso-calledpolygeneticdiseasesformorethantwentyyears,theyhavelearnedthatfindingthegenesthatcontributethemosttoadiseaseisquitedifficult.Type2diabetesisnoexception,especiallyconsideringtheimportanceofenvironmentandlifestyleinthedisease.Thisdoesnotmeanthatscientificresearchhasyieldednonewinformationaboutthegeneticcontributiontodiabetes.Quitethecontrary!Researchershavemadeagoodstartinidentifyingthegenesinvolved.

Recently,threeinternationalgeneticstudiesexaminedthegenesinvolvedininsulinsecretionfrompancreaticcellsaswellashowinsulinactsoncellsinthebody.3Thesestudiesfoundatleasttengeneticvariantsindiabeticpopulations,eachoneofwhichcontributessmallamountstothepredispositionforthedisease.ItisnotknownwhetheranyofthesevariantssuggestanovelapproachtotreatingType2diabetes.Moreextensiveresearchisrequired.

UnderstandingtherelationshipbetweenobesityandType2diabetesiscritical.Thekeytothisrelationshiparethecellsinthebodyand,interestingly,inthebrain.Overthepastdecade,researchershavelearnedagreatdealaboutthevarietyofsubstancesthatcontrolappetite,includinghormones.4

Hormonesactonreceptorstoexerttheirfunctions.Oneofthesefunctionsisappetite.Receptorsarespecializedentitiesonsurfacesofcellmembranesthatactspecificallyforonlyonehormone,similarlystructuredhormones,orsyntheticcompounds.Thinkofthehormone-receptorinteractionasakeyandalock.Onlyonekey(orkeysverysimilartoit)willunlockthedoorsothehormonewillrespondappropriately.

Onesuchhormone,calledleptin,regulatesappetitethroughaninteractionwithareceptor.Researchershavefoundthatwhenbloodleptinlevelsarehigh,weeatless,andwhentheyarelow,weeatmore.Whenweeat,leptinlevelsincrease.Theabilityofthishormonetotelluswhenwearefulldependsonitsactiononcertainreceptors,however.Ifthesereceptorsdonotrespondappropriatelytoleptin,apersoncaneatmorefooddespitebeingfull,andobesitycanresult.Obesepeopleoftenhavehigherleptinlevels,whichcorrelatewithinsulinresistance.Thereceptorsmayrespondlesstoagivenamountofleptin,andthebodythensecretesmoreofit.Exactlyhowchangesinleptinlevels,otherproteins,andeveninflammatoryresponsescauseorrelatetoinsulinresistanceanddiabetesisnotknown.However,thestudyofleptinlevelsisapromisingareaforfuturediabetesresearch.5

Anotherfactorininsulinresistanceresidesinthebrain.Thebrainregulatesfoodintakebyrespondingtolevelsofinsulinandleptinintheblood,aswellastoglucoseandcertaintypesoffatcalledfreefattyacids.Whenthebraindetects

toglucoseandcertaintypesoffatcalledfreefattyacids.Whenthebraindetectsthattheactionsofthesehormonesaresufficient,ittellstherestofthebodythatitneedstoconsumelessfood.Conversely,whenthesesignalsareinshortsupply,thebrainpromotesincreasedfoodconsumption.Ifthebraincannolongerkeepfoodintakewithinnormallimits,weightgainandinsulinresistancecanresult.Howdoesthishappen?

Itturnsoutthatthebrainhasinsulinreceptorsthatcanbecomeresistanttoinsulin,justasinsulinreceptorsinperipheraltissuescan.Infact,thebiochemicalpathwaysthatmediatetheactionsofinsulinappeartobesimilarinboththebrainandperipheraltissues.Likeperipheraltissues,thebrainreceptorsbecomemoreresistanttoinsulinwithexcessfoodconsumption.Thus,thebrain’scontroloffoodintakeisimpaired,resultinginobesity.Thebrainrespondstoleptininthesamewayastissuesdoelsewhereinthebody.HowobesitycanleadtoType2diabetesisamultifacetedprocess.

So,howdoesallthisaddup?Whenweeat,foodispartiallyconvertedintoglucosetofeedthebody’scellsandtoprovidetheenergytheyneedtooperate.Totransportglucoseintothecells,thepancreassecretesinsulin,therebyregulatingourbloodlevelsofglucose.Ifweeattoomuchfoodoveralongperiod,thecells,includingthoseinthebrain,becomeresistanttotheconstantbombardmentoftoomuchinsulin.Inaddition,thereleaseofleptintocontrolourfoodintakenolongercontrolsourappetite,andwedevelopresistancetoleptin.Finally,wheninsulinproductionisinsufficienttomoveglucoseintocells,glucoserisestodangerouslevelsinthebloodandcanresultinType2diabetes.

Wehaveseenthattherearemanyphysiologicalmechanismsthatcanleadtoobesityanddiabetes.Geneticdefects,too,cancontributetotheultimateexpressionofType2diabetes.Whenthesegeneshavebeenidentified,itislikelythatmedicationscanbedevelopedthatwilltargettheexpressionofthesegenes,potentiallycontrollingexcessivefoodintake.

Howdoesdiabetesleadtokidneyfailure?Theprocess,technicallyknownasdiabeticnephropathy,typicallydevelopsoveraperiodoftentotwenty-fiveyears.Itstartswhenexcessglucoseintheblooddegradesthefilteringcapacityoftheglomerulusinthekidney(seechapter2).Normally,theglomeruluswillallowonlysmallmolecules,likewaterandsalts,topassthrough,leavingbehindlargemoleculeslikeproteins.Smallamountsofproteinexcretedintheurine,aconditioncalledmicroalbuminuria,isoftenthefirstsignofdiabetes.(Asignissomethingadoctorcanidentifythroughtesting.Asymptomissomethingthepatientexperiencesornotices.)Kidneyfunctionisgenerallynormalatthisstage.

However,ifthedeteriorationofthefiltrationofbloodthroughtheglomeruluscontinues,increasingamountsofproteinpassintotheurine.Calledmacroalbuminuria,thisexcessexcretionofproteincancausescarringoftheglomerulusandcanleadtodecliningkidneyfunction.

Howhighglucoseconcentrationsdegradekidneyfunctionisnotcompletelyunderstood.Nevertheless,researchershavediscoveredanumberofpotentialbiochemicalpathwaysthatarestimulatedbyglucose.6Thesepathwaysseemtounderliethegrowthofsomecellsintheglomerulusandtubulesthatleadtoscarringandfiber-liketissue,therebydegradingkidneyfunction.Iftheseprocessescontinuelongenough,kidneyfailurecanresult.

Hypertension

Hypertension,orhighbloodpressure,isthesecondleadingcauseofkidneyfailure,accountingfor24percentofcases.Bloodpressurethatistoohighcandamagekidneysandcausethemtoultimatelyfail.(Highbloodpressureisdefinedbelow.)

Whentheheartpumpsbloodthroughthebloodvessels,thebloodpushingagainstthewallsofthesevesselsincreasesthepressure.Twonumbersexpressthispressure:oneispressurewhenthehearthascontracted(knownasmaximum,orsystolic,pressure),andtheotheristhepressureaftertheheartrelaxes(knownasminimum,ordiastolic,pressure).

Bloodpressurecanbemeasuredusingabloodpressuremonitor.Abloodpressurecuffiswrappedaroundtheupperarm.Thecuffisinflatedusingapumpuntilthepulseintheupperarmisnolongerfelt.Thecuffisslowlydeflateduntilthesoundsofheartbeatsareheard.Thepressureatwhichthesoundsarefirstheardisthesystolicpressure,whereasthepressureatwhichsoundsarenolongerdetectableisthediastolicpressure.Thebloodpressuremonitorprovidesareadoutoftwonumbers.Themeasuredbloodpressureisexpressedasaratioofthesetwonumbers,like120/80(systolic/diastolic,or“systolicoverdiastolic”).

Abloodpressureatorbelow120/80isconsiderednormal.Highervaluesmaybeevidenceofhighbloodpressure,orhypertension.Hypertensioniscategorizedasmoreorlessseverebasedonthedegreeofpressureelevation.AccordingtotheNationalInstitutesofHealth,ifthesystolicpressurereaches120to139orthediastolicpressurereaches80to89,apersonispre-hypertensive.Peoplewithsystolicpressuresof140andabove,ordiastolicpressuresof90orabove,areconsideredhypertensive.Ineithercase,medicationsand/orlifestylechangesarenecessarytocontrolbloodpressure.

Asweseeinfigure3.3,twofactorscontributetothedevelopmentofhypertension:theamountofbloodflowingthroughvesselsandthevessels’diameter.Thesefactorsaffecteitherthesystolicorthediastolicpressures.Theamountofbloodflowingthroughbloodvesselsresultsfromthevolumeofbloodleavingtheheartwitheachcontractionandtheheartrate.Thehigherthevolumeofbloodexpelledorthehighertheheartrate,thehigherthesystolicbloodpressure.Thediameterofthebloodvesselsaffectsbloodpressurebyresistingbloodflow.Thesmallerthediameterofthevessels,thehigherthediastolicbloodpressure.Thisisanalogoustoputtingyourthumboverthetipofahosewithrunningwater.Constrictingthehosenozzlewithyourthumb,youcanfeelthewaterpressurebuild.Onereasonthatvesselsmaybesmallisbecauseofblockagesduetoatherosclerosis(abuildupofplaquewithinthevessels).Thereareotherreasons,likeotherunderlyingmedicalproblems,andappropriatemedicaltreatmentisdeterminedbythecauseofhypertension(seechapter5).

Figure3.3.FactorsinHighBloodPressure

Bloodpressureisnotjustinfluencedbyphysiologicalfactorslikevaryingheartratesandthemusculartoneofbloodvessels.Geneticsusceptibilitymayalsoinfluenceaperson’sbloodpressure.Justasindiabetesresearch,determiningwhichspecificgenesareresponsibleforbloodpressureandtheirrelativecontributiontohypertensionhasbeenverydifficult.7Researchersdonotexpectthatamutationinasinglegeneisresponsibleforhypertension.Mostlikely,theinterplayofmanygenespromoteshypertension.Environmentandlifestylecanalsocontributetohypertensionthroughacomplexgene-environmentinteraction.Oneexampleofthistypeofinteractionisexcessivesalt(sodium)intakeandretention.

Excesssaltintakecanleadtohypertension.However,eachpersonrespondstosaltdifferently.Attheextremes,somepeopleareverysensitivetosalt,whereassomeareinsensitive.Thesedifferencessuggestthatsaltsensitivityhasageneticcomponent.Aswelearnedinchapter2,therenin-angiotensinsystemevolvedtocombatdehydrationbyretainingsodiumandmaintainingbloodpressurewhenthebodylosessodium.Inthissystemalone,itispossiblethatmanygenescouldbealteredinawaythatpromoteshypertension.

Researchongenesunderlyinghypertensionisstillinitsinfancyandwillrequiremanymorestudiestoidentifythespecificgenesresponsible.Futureresearchmayalsoyieldnewmedicationstoreducehypertension.Becausehypertensionplayssuchanimportantroleinkidneydisease,thesenewmedicationsmaygivephysiciansbettertoolstopreventkidneyfailure.

Obesitycontributestohypertensionaswellaskidneydamageinducedbyotherdiseasesdiscussedinthischapter.Kidneydiseasesthemselvesareassociatedwithincreasedbloodpressurebyavarietyofmechanisms.Obesepeopleoftentakeinanexcessiveamountofsalt,whichcanleadtohypertension.Thehighpressureontheglomeruluscanslowlydegradeitsfilteringcapacityandprecipitatereactionssimilartothosethatoccurindiabetes-inducedkidneyfailure.Inaddition,accumulatingfatcancontributetohypertension.Consideringthatobesity,hypertension,anddiabetesoftenaccompanyoneanother,itishardtoknowwhichproblemcamefirst.However,obesityisoftentheprimarycauseofhypertensionanddiabetes.

Weknowthathypertensionslowlydestroysthekidneys’abilitytofiltertheblood,buthowdoeshypertensionleadtokidneyfailure?Withprolongedhypertension,theexcesspressurecaninjuresmallbloodvesselsinthekidneyandcandestroythefilteringabilityoftheglomerulus(seechapter2),leadingtokidneyfailure.Usingthehosemetaphor,ifyouattachcheeseclothtightlyover

theendofthehose,waterwillflowthroughthecheeseclothwithoutharmingit.Butifyoupinchthehose,increasingtheflowpressure,thecheeseclothwillbegintodegradeandeventuallyrupture.

GlomerularDiseases

GlomerulardiseasesareacomplexsetofdisordersandarethethirdleadingcauseofkidneyfailureintheUnitedStates,accountingfor15percentofcases.Glomerulardiseaseoftenresultsininflammationoftheglomerulus,whichcaneventuallycausetheformationofscartissue.Asaresult,proteinleaksintotheurineinsteadofbeingabsorbedbackintocirculation.Likediabetesandhypertension,glomerulardiseasesslowlydestroythefilteringabilityoftheglomerulus.Excesspressureonthesensitiveglomeruluscanleadtokidneyfailure.Thethreemaincausesofglomerulardiseasesareautoimmunediseases,hereditarynephritis,andinfections.

Thebody’simmunesystemprovidesthefirstlineofdefenseagainstinfectionsbygeneratingantibodiesandimmunoglobulins.However,therearetimeswhenantibodiesandimmunoglobulinscauseharmtothebody,whichcanleadtoanumberofmedicalproblems.Oneofthesecomplicationsisthedepositofantibodiesintheglomeruli,causinginflammation.

Manyautoimmunedisorderscontributetoglomerulardiseases.OneofthesediseasesisimmunoglobulinA(IgA)nephropathy.IgAnephropathyisthemostcommoncauseofglomerulardiseasesnotrelatedtothepresenceofanotherdisease.WithIgAnephropathy,IgAdepositsontheglomerulus,causinginflammation.IgAnephropathyaffectsmenandwomenofallagegroupsequally.Whenaconsiderableamountofproteinappearsintheurine,controllingbloodpressurehelpsmanagethesymptomsandmayslowtherateofdeteriorationofkidneyfunction.

Lupuserythematosus,anotherautoimmunedisease,primarilyinvolvesinflammationoftheskinandjoints.Thisdiseaseaffectsmorewomenthanmen.Whenlupuserythematosusattacksthekidney,autoantibodiesformoraredepositedintheglomeruliandcausescarring.Drugsthatsuppresstheimmunesystemaregenerallyusedtotreattheinflammationinthekidney.

OneinheritedformofglomerulardiseasesisAlportsyndrome.Alportsyndromenotonlyaffectsthekidneybutmayalsoimpairvisionandhearing.Moremenhavedifficultywiththisdiseasethanwomen,experiencingadeclineinkidneyfunctionintheirtwentiesandreachingtotalkidneyfailurebyage40.

Glomerulardiseasesarealsocausedbyinfectionsinotherpartsofthebody.

Similartowhathappensinautoimmunediseases,thehighnumberofantibodiesproducedtocombattheseinfectionscandepositinthekidneysandreducekidneyfunction.Althoughinfectionsusuallydonotcausepermanentdamage,peoplewithchronicinfectiousdiseaseslikeHIV/AIDSandhepatitisChaveariskofdevelopingchronickidneyfailure.

FocalsegmentalglomerulosclerosisisanotherglomerulardiseasethatdisproportionatelyaffectsAfricanAmericans.Itresultsinscarringoftheglomerulusorclusteringofglomeruliinaspecificsegmentofthekidney.Focalsegmentalglomerulosclerosiscanbedifficulttodiagnoseandtreat.Biopsiestosearchforscarringinkidneytissuearethebestmeansofadiagnosis.(Abiopsyisaprocedureinwhichasmallamountoftissueisremovedfromthebodyforinvestigationandtesting.)However,ifthebiopsysampleisfromanunaffectedareaofthekidney,scarringwillnotbeevident.Thus,repeatedbiopsiesindifferentsegmentsofthekidneyareneededtoconfirmadiagnosisoffocalsegmentalglomerulosclerosis.

PolycysticKidneyDisease

Polycystickidneydisease(PKD),thefourthleadingcauseofkidneyfailure,accountsforabout5percentofpeoplewithkidneyfailure.InPKD,small,fluid-filledcystsdevelopinthekidneys,sometimesevenbeforebirth.Thesecystsgrowlargeenoughovertimetocausekidneyfailure.Becausethecystscangrowsolarge,physiciansusedtothinkPKDwasaformofkidneycancer.

AccordingtothePKDFoundation,PKDaffects600,000Americansofbothgendersandallethnicgroups.PKDhasthestrongestgeneticlinktoakidneydisease.Althoughitcanoccurspontaneously,mostpeoplegetPKDbyinheritingit.Infact,PKDisoneofthemostlife-threateninginheriteddiseases.BecausePKDisprimarilyinherited,researchhasidentifiedthegenesandtheircorrespondingproteins.Asaresult,acureforPKDmaybefoundinthenearfuture.

PeoplewithPKDinheritthediseasefromoneorbothoftheirparents,dependingontheformofthedisease.PKDcomesintwoforms:autosomaldominant(ADPKD),themorecommonformofthedisease,andautosomalrecessive(ARPKD).

Genetically,thedifferencebetweenADPKDandARPKDisthenumberoffaultycopiesinherited(seefigures3.4and3.5).PeoplewithADPKDinheritthemutatedgenefromonlyoneparent,whereaspeoplewithARPKDinheritonemutatedgenefrombothparents.ThegeneinheritedinARPKDisdifferentfrom

theoneinheritedinADPKD.ADPKDisverycommon,affecting1in500people.Becauseapersonneeds

toinheritonlyonecopyofanabnormalgenefromoneaffectedparenttogetADPKD,thechanceofinheritingPKDwhenoneparenthasthedefectis50percent.Becausebothparentsmusthavethemutatedgene,inheritingARPKDismuchlesscommon,affecting1in20,000peopleinthegeneralpopulation.WithARPKD,ifonlyoneparentcarriesthemutatedgenewithouthavingthediseasehimself,childrenwillnotdevelopARPKDbutmaypassonthemutatedgenetotheirchildren.ApersonwithparentswhobothhaveamutatedARPKDgenehasonlya25percentchanceofinheritingthedisease.

ADPKDandARPKDalsodevelopdifferently.TheonsetofADPKDcanoccuratanyagefromthelateteenstothemid-thirties,withkidneyfailuregenerallydevelopingbetweenthemid-fortiesandmid-fifties.Becausetherateofcystformationisvariable,apersonwithADPKDmaynotneeddialysisuntilanadvancedage.SometimesADPKDisdiagnosedunexpectedlyduringaroutinephysical,whereabnormallabresultssuggestkidneydisease.Moretestswouldbeneededforadefinitivediagnosis(seebelow).ARPKD,incomparison,oftenprogressesbeforebirth.ApersonwithARPKDcanonlysurviveintoadulthoodwithdialysisortransplantation.InthisbookIusethetermsADPKDandPKDinterchangeably,sincetheincidenceofARPKDissolow.

Figure3.4.AutosomalDominantInheritanceofPKD(ADPKD)

Figure3.5.AutosomalRecessiveInheritanceofPKD(ARPKD)

DuringthelastdecaderesearchhasrevealedthegeneticunderpinningsofPKD.Twogenes,PKD1andPKD2,accountforvirtuallyallcasesofPKD.MutationsinPKD1accountfor85percentofPKDcases.InmostoftheothercasesofPKD,mutationsinPKD2areresponsible.

Althoughthediseasecausedbyeachmutatedgeneissimilar,peoplewithPKD2mutationstendtoprogresstowardkidneyfailurelaterinlifethanpeoplewithPKD1mutations.Inaddition,peoplewithPKD2mutationshavefewerrenalcystswhendiagnosedandarelesslikelytohavehighbloodpressure.PeoplewithPKD1mutationsexperiencekidneyfailureearlierinlifebecausetheyhavemorecyststhanpeoplewithPKD2mutations.

Genesmakeproteins.PKD1andPKD2maketheproteinspolycystin-1andpolycystin-2,respectively,whichplayacrucialroleinthegrowthofcysts,thoughwedon’tyetknowexactlyhow.ResearchhasshownthatthetwoproteinsareattachedtooneanotherandthatmutationsineithergenecancausePKD.AlthoughamutationinthegenesandimproperworkingoftheproteinsarenecessaryforPKDtoprogress,otherunknownfactorsmayexplainwhythediseasedevelopsdifferentlyacrossfamiliesandevenwithinfamilies.

Howrenalcystsformandgrowiscurrentlyunderintensescientificinvestigation.Epithelialcellsliningthetubulesinthekidneysareactivelyinvolvedinreabsorbingnutrientsandwater(seechapter2).InPKD,1to2percentofepithelialcellsreproducemanytimesandeventuallyformnumerouscysts.Thesecystsfillupwithfluidandeventuallypressagainstthenephronssothatnourinecanpassthroughthem.Whenenoughnephronsareblocked,thekidneysceasetofunction.Thecyststhatforminthekidneyscanbecomequitelarge(seefigure3.6).Anormalkidneyweighslessthanapound.Apolycystickidneycanweighupto38poundsandmayproduceaprotrudingabdomen.

Untilrecently,earlydiagnosisofPKDhadbeendifficult,butnownon-invasivetechniqueslikeultrasound,computerizedtomography(CT)scans,andmagneticresonanceimaging(MRI)scansareusedtoidentifyrenalcysts.8UltrasounddetectsADPKDinmostpeopleby30yearsofage.However,ultrasoundmaymisssomecasesinvolvingthePKD2gene.CTscansproduceclearerimagesbutrequireexposuretoradiationandcontrastdyes.

Figure3.6.APolycysticKidney(left)CanBeMuchLargerThanaNormalKidney(right)

Source:PKDFoundation.

Arecentstudyfoundthatmeasuringincreasesinkidneysize(cystvolume)usingMRIscansisthebestmethodofdiagnosingandfollowingtheprogressionofPKD,andwasanexcellentpredictorofthelossofkidneyfunction.9UsingMRIscanstomeasurekidneysizeisnotyetpartofgeneralclinicalpractice,butthisapproachcouldprovidemoreprecisemeasurementsofdiseaseprogressionandoftheeffectivenessofmedicaltreatments.

Likediabetes,PKDcanhavenumeroushealthconsequences.Kidneycystscanbequitepainfulandmayrequiresurgery.PeoplewithPKDmayhavebloodintheurine,frequentkidneyinfections,andurinarytractinfectionsthatrequirehospitalization.Insomecases,thekidneysmustberemoved.

PeoplewithPKDmayalsohavecystsformintheliverorotherorgans.Thecystscanbecomelargeanduncomfortable,especiallyinwomen,requiringremovalofpartoftheliverordrainageofthefluidinthecysts.

ApotentiallyfatalcomplicationofPKDistheballooning(calledananeurysm)andruptureofamajorbloodvessel,especiallyinthebrain.Aneurysmsoccurin5to10percentofpeoplewithPKD.Whereafamilyhistoryofaneurysmsexists,theriskofaneurysmrisesto20percent.Modernimagingtechniquescandetectaneurysmsbyvisualizingaffectedbloodvessels,andpeoplewithPKDshouldbetestediftheyhaveafamilyhistoryofaneurysms.Iffoundearly,aneurysmsofacertainsizecanberepairedsurgically.Smallaneurysmsaremonitoredwithperiodicscans.

GeneticTestsBecausegeneticinfluencescontributetoallfourcausesofkidneyfailurewehavediscussed,cantestsidentifypeoplewhoare(orwhosedescendentsare)atriskofdevelopingkidneydisease?Wouldatesthelpthesepeoplemodifytheirlifestyletoreducetheirchancesofgettingkidneydiseaseordevelopingkidneyfailure?Perhaps.Somegenetictestscanfindthegenesthatcausediseaseslikediabetes.Butbecausesomanygenescancontributetoeachdisease,itisnotclearatthistimehowvaluablesuchtestswouldbe.

PKDisanexceptionbecausethegenesforthediseasehavebeenidentified.AgenetictesthasbeendevelopedbyAthenaDiagnostics(www.renaldx.com)tosequencePKD1andPKD2andtolookformutations.Thetestiseffectiveonly70percentofthetime,however,sotheresultsarepossiblymisleading.SometimestheresultsgiveafalsepositiveforthepresenceofPKD.Conversely,

theresultscanmissactualcasesofPKD.Resultsofthesegenetictestsshouldbeconfirmedbyanultrasound.

Althoughgenetictestinghasitsadvantages,therearedisadvantagesthatmightdetersomepeoplefrombeingtested.Onedrawbackoffindingoutyouhaveadiseaseistheemotionalburdenthatknowledgebringswithit.SincethereislittleyoucandoabouthavingPKD,otherthangoodmedicalmanagementforsymptomslikehypertensionanddrinkingalotoffluid,whatpurposewouldbeservedbyknowing?AdiagnosisofPKDmaymakeitdifficulttoobtainmedicalandlifeinsurance.IfyoudonothavecontinuousemploymentasIdid,anewemployermaynotprovideadequateinsurance.Ifyouareunemployed,youmaynotbeabletoobtaininsuranceatall.HavingadefinitivediagnosisofPKDmaynotbeusefuluntilsignsofkidneyfailureorothersymptomslikehypertensionorkidneycystsappear.Recentlylegislationtobargeneticdiscriminationinobtainingmedicalinsuranceandemploymentwassignedintofederallaw,theGeneticInformationNon-DiscriminationActof2008.Currentlyitisnotclearhowwellthelawwillbeenforcedorwhetheritwillfacelegalchallenges.Inaddition,CongresspassedthePatientProtectionandAffordableCareActin2010thatprohibitsexcludingpeoplewithpreexistingconditionsfromobtaininghealthinsuranceby2014.

PeoplewithPKDmayhavetroubledecidingwhethertohavechildren.Althoughchildrenhavea50-50chanceofnotinheritingaPKDmutatedgenefromanaffectedparent,theyalsohavea50-50chanceofinheritingthedisease.Theseoddsarehighenoughtogivesomepeoplepausebeforedecidingtostartafamily.ParentscantakesolaceinthehopethatacuremightemergefortheirchildrenwithPKD.Inmyownfamily,mymotherdiedprematurelyatage44,whendialysisandtransplantationwerenotavailable.Nowinmysixties,Ihavesurvivedwithasuccessfulkidneytransplantandamlivinganormallife.Today’smedicinecantreatkidneyfailure,anemia,highbloodpressure,andothercomplicatingfactorsofthedisease.Inmymother’sday,noneofthesetreatmentsexisted.Tomorrow’smedicinemaybemuchmoreadvanced,andatreatmenttopreventcystformationorgrowthmaybeavailable,relievingourchildrenoftheburdenofPKD.

Thereishopeforbettertreatmentoptionsinthefuture.

4DIAGNOSINGANDMANAGINGKIDNEY

DISEASE

Everypersonshouldgetacheckupwithaprimarycarephysicianatleastonceayear.Itmaybewhileyouarehavingoneoftheseannualcheckupsthatyourdoctordiscoversthatyouareatriskforkidneydiseaseorthatyoualreadyhavekidneydisease.Althoughkidneydiseaseusuallyhasnosymptoms,likefatigueorpain,aphysicalexaminationcandeterminewhetheryouhavehighbloodpressure,bloodintheurine,ordecreasedkidneyfunction.Athoroughmedicalhistoryhelpsyourdoctorknowwhetheryouhaveapredispositiontokidneydiseaseorafamilyhistoryofdiseasesthatcanleadtokidneydisease,likediabetes,highbloodpressure,orpolycystickidneydisease(PKD).

Ifyouhaveoneormoreoftheseriskfactors,yourdoctormayorderadditionalscreeningtests.TheNationalKidneyFoundation(NKF)hasdevelopedascreeningprogramforriskofdevelopingkidneydiseasecalledtheKidneyEarlyEvaluationProgram(KEEP).Yourdoctormayusecertainmeasurestoassessyourriskandtofindanyevidenceofkidneydiseaseandwhetherithasprogressed.Table4.1liststhemeasuresofassessingrisk.Screeningtypicallyconsistsofurinalysis(lookingforproteinorbloodintheurine)andmeasuringcreatinineorotherfactorsintheblood.Withameasureofbloodcreatinine,yourdoctorwillcalculateyourglomerularfiltrationrate,ameasureoftheabilityofyourkidneystofiltertoxinsfromyourblood.Theresultsofthesetestsmaycauseyourdoctortosuspectthatyouhavekidneydisease.Adefiniteplusisthattheresultsofthetestsmayprovideanearlywarning,soyourdoctorcanhelpyouprotectyourkidneysfromfurtherdamageandeducateyouabouttreatmentoptionsorchangesinlifestyle.Forexample,yourdoctormayrecommendthatyouloseweight,stopsmoking,orcontrolyourbloodpressure.

Table4.1KidneyEarlyEvaluationProgram(KEEP)ScreeningMeasures

Beingdiagnosedwithanydiseasecanbeterrifying.Ifyouarediagnosedwithkidneydisease,gatherasmuchinformationasyoucanaboutyourconditionandmedicalcare,findwaystoreducetheprogressionofkidneydisease,andplanyourfuture.Takeanactiveroleinyourcare.Itwillgoalongwaytowardhelpingyoufeelmoreincontrol.Thischaptercoverssomeofthediagnostictoolsandtreatmentsinvolvedwithyourmedicalcare.

DiagnosticsDoctorsmonitorkidneyfunctionintheirpatientsbymeasuringsubstancesinthebloodandurineusingseverallaboratorytests:bloodureanitrogen(BUN),orjusturea,creatinine,creatinineclearance,andglomerularfiltrationrate(GFR).Toperformthesetests,yourhealthcareproviderwilldrawsmallamountsofbloodandwillaskyouforaurinesample.

Ureaandcreatinineinthebloodaremeasuresofthemainproductsofproteinmetabolism.Howconcentratedthesesubstancesareinthebloodindicateshoweffectivelyyourkidneysremovewasteproducts.Normalconcentrationsofthesesubstancesare15to25mg/dlforBUNand0.5to1.3mg/dlforcreatinine(mg/dl[milligramsperdeciliter]referstotheamountofasubstanceinabitmorethan3ouncesofblood).Valueshigherthanthatrangeforeithermeasurementmeanthatkidneyfunctionisdeclining.

thatkidneyfunctionisdeclining.Abloodureanitrogen(BUN)testmeasuresthequantityofnitrogeninyour

bloodthatcomesfromthewasteproducturea.ABUNisperformedtoseehowwellyourkidneysarefunctioning.Ifyourkidneyscan’tremoveureafromtheblood,yourBUNlevelwillrise.

Measuringcreatinineclearancecandeterminehowmuchcreatinineyourkidneysremovefromyourbodyaswellashowwellyourkidneysarefunctioning.Creatinineclearanceisamoreprecisemeasureofkidneyfunctionthanrelyingonbloodmeasurementsalone.Toperformacreatinineclearancetest,yourdoctorwillaskyoutocollectyoururineoveratwenty-four-hourperiodinalargecontainer.Alaboratorywillthenanalyzeyoururineforcreatinine.Inadditiontoaurinalysis,asmallamountofyourbloodwillbeanalyzedforcreatinine.Yourcalculatedcreatinineclearanceisexpressedasthevolumeofbloodyourkidneyscompletelyclearofcreatinineperminute.Anormalcreatinineclearancerangesfrom90to130ml/minute.Askidneyfunctiondeclines,creatinineclearancealsodrops.Glomerularfiltrationrate(GFR),thepreferredmethodforassessingkidney

function,isatestsimilartocreatinineclearance.YourdoctororalaboratorycanestimateGFRfrombloodcreatinine—takingintoaccountage,gender,race,andbodymass—usingtheGFRcalculatorprovidedbytheNationalKidneyFoundation(http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm;orgotowww.kidney.organdlinktothecalculatorfromthere).Likecreatinineclearance,GFRprovidesmoreaccurateinformationaboutkidneyfunctionthanbloodcreatininealonedoes.Normalvaluesare80to120ml/minute/1.73m2.Fromthevalueobtained,yourdoctorcandeterminethestageofyourkidneydiseaseandcaneasilymonitoritsprogressionwithouthavingtoobtainatwenty-four-hoururinecollectionfromyoueachtimeyourbloodcreatinineismeasured.Inaddition,shecanusethisinformationtoplanyourtreatment.

Oncekidneyfailurehasbeenrevealedthroughoneofthetestsdescribedabove,yourdoctormayreferyoutoanephrologist.TheNationalKidneyFoundation’sguidelinessuggestthatpatientsbereferredtoanephrologistwhentheirGFRislessthan30.Yourdoctormayalsoreferyoutoanephrologistifheisnotabletoperformalltheappropriatediagnostic,treatment,andmanagementrecommendationsforkidneyfailure.

Ifyouarehappywithyourdoctor,thenherrecommendednephrologistwillprobablybesomeoneyoucometotrustaswell.Butpersonalinteractionsaresubjective,anddifferentpatientsmayviewthesamedoctordifferently,forall

kindsofreasons.Ifyousensethatyouarenotgettingthenephrologist’sfullattention,orifthenephrologistwillnotexplainterms,concepts,orthemedicalcarebeingrecommended,orifyoufeelthatyourconditionisnotbeingproperlymanaged,youmaywanttoconsidergettingasecondopinionfromanothernephrologist.Itmaybethatyouwillwanttoswitchdoctors,orthesecondopinionmayreinforceyourconfidenceinyourcurrentnephrologist.

Table4.2displaysthestagesofkidneydiseaseandoutlinesageneralactionplanthatyourdoctormayuseforeachstage.Stage1isdefinedasthestagewhenGFRis90orhigherbuttherearemarkersofkidneydamage,likeproteinintheurineorkidneycystsinpeoplewhohavePKD.Yournephrologistwillcheckyourheart’shealthandwilllookforanyothercardiovascularissues.AtStage1yournephrologistwillconcentrateonfindingthecauseofyourkidneyfailureandontreatinganyunderlyingdisease,likediabetes.

Stage2isclassifiedbyaGFRof60to89.Inadditiontogivingyouadiagnosisofyourstage,andtreatingyou,yournephrologistwilltrytoslowthedeclineofyourkidneyfunction,perhapsprescribingmedicationstocontrolyourbloodpressureortohelptreatotherunderlyingdiseases.DuringStages1and2,youmustfollowyourdoctor’srecommendations,evenifyoudon’tfeelsick.Bydoingso,youhavethegreatestchanceofpostponingthecompletelossofkidneyfunction,perhapsindefinitely.Inaddition,youmayhavenosymptomsofkidneydiseaseandyoumayfeelwellenoughtoliveanormallife.

AtStage3,withaGFRof30to59,therearemoreevidentcomplicationsofchronickidneydisease.Forexample,youmaybecomeanemic,showevidenceofbonedisease,orhaveapoornutritionalstatus.Althoughitmaybeyearsbeforeyourkidneyscompletelyfail,ifatall,yournephrologistwilldiscusswithyouthetreatmentoptionsforkidneyfailure,includingdialysisandtransplantation.

Table4.2SampleClinicalActionPlanforChronicKidneyDisease

IfyoureachStage4,withaGFRof15to29,yournephrologistwillprepareyoufordialysisbyexplainingtheprocessandwillhaveyouevaluatedforakidneytransplant(seechapters6and7).Hewillexplainthedrawbacksandbenefitsofthesetreatmentsandhelpyoudecidewhichoneisbestforyouandyourlifestyle.It’sapainfulfactthatatransplantmaynotbeavailableforyears,ifyoudon’thaveadonor.Yourdoctorcanhelpyouplanhowtointegratethesetreatmentsintoyourlifetomakethemasunobtrusiveaspossible.

Stage5,whenGFRislessthan15,meansthatyoumusthavedialysisortransplantationtolive.

Serumcreatininelevelsareausefulgaugeofkidneyfunction,butbythemselvestheyarenotareliableindicationofdisease.Assessingthedegreeofkidneydeclinesolelyfromtheselevelscanbeverymisleading.Whenfollowedovertime,theymayappeartoriserapidly.However,calculatingtheGFRsforthesevaluescanprovideadifferentpicture.Changesinserumcreatininefrom1to2inthenormalrangerepresentmuchlargerpercentagechangesinGFRthanwhentheyrisefrom3to4.Whileonthesurfaceitwouldseemthatachangein

whentheyrisefrom3to4.Whileonthesurfaceitwouldseemthatachangeinthehigherlevels(3and4)wouldcausemoreconcernthananincreasefrom1to2,wehavetoconsiderthata100percentchange(from1to2)islargerthana33percentchange(from3to4).Itcouldbemanyyearsbeforeyouwillneeddialysisortransplantation.Thus,itisnotthatkidneyfunctionhasdeclinedfaster,itjustseemsthatwaybecauseyouareonlylookingatcreatinine,notGFR.Inotherwords,yourkidneyfunctionisnotdecliningasfastasyoumayfearitis.

Yourdoctorwillalsodeterminewhetheryouareanemic(seechapter2).Redbloodcells,hemoglobin,andhematocritareallfactorsindiagnosinganemia.Hemoglobinisaproteininredbloodcellsthatcarriesoxygenfromthelungstotherestofthebody.Normalhemoglobinconcentrationsarebetween14.0g/dland18.0g/dl.Hematocritmeasuresthepercentageofbloodvolumeoccupiedbyredbloodcells.Normalhematocritvaluesare40to54percentformenand37to47percentforwomen.Lowhemoglobinorhematocritvaluesmaymeanyouhaveanemia,aconditionthatiscommoninmoreadvancedstagesofkidneydisease.

YourNephrologistOnceyouhavebeenreferredtoanephrologist,hewillbecomeyourprimarycareprovider,eventhoughyourfamilyphysicianwillcontinuetobeinvolvedinyourgeneralcare.Yournephrologistmaybeoneofseveraldoctorsprovidingyourhealthcare,dependingontheunderlyingdiseasecausingyourkidneyfailure.Forexample,ifyouhaveheartdisease,acardiologistmaybemonitoringyourcardiachealth;ifyouhavediabetes,anendocrinologistmaybemanagingyourbloodsugar;ifyouhavelupus,arheumatologistmaybetreatinginflammation.Ideally,allofyourdoctorswillworktogetherasateamandwillcommunicatecloselywithyouandwithoneanother.

Thestageofkidneydiseaseandthecauseofkidneydiseasedeterminetherecommendedtreatment.Manypeopledonotseeanephrologistuntiltheirkidneydiseaseisfairlyadvanced,becausetheydonotknowtheyhavekidneydiseaseuntilitreachesalaterstage.Butifyoudoseeanephrologistatanearlystage,hecanfocusontheunderlyingcauseandpossiblyintervenetoreducetheprogressionofkidneyfailureaswellasmanageanysignsandsymptomsyoumayhave.

Afirstvisittothenephrologistwillincludeathoroughexaminationofyourmedicalrecords,aswellasassessmentsofyourkidneyfunction,urine,oranydiagnosedkidneydisease.Ifyouhavenodiagnoseddisease,yournephrologist

willbeginbyidentifyingtheprimarycauseofyourdecliningkidneyfunction.Inaddition,assumingthatthenephrologisthasruledoutacuteorshort-termkidneyfailure,shewillwanttoknowyourstageofchronickidneydisease.Withadiagnosis,thenephrologistcanworktodecreasetherateoflossofkidneyfunction,tocontrolyourbloodpressure,and,dependingonthestageofkidneydisease,tomanageanycomplications.(ComplicationstypicallybeginwhenyourGFRisbelow60.)Yournephrologistmayalsorecommendmagneticresonanceimaging(MRI)ofyourkidneystomeasuretheirsizeortolocatecystsorstones.Akidneybiopsymaybenecessarytomakeadiagnosisandtohelpdeterminethebestwaytotreatyou.

Askyournephrologistanyquestionsyouhaveaboutyourdisease.Sheshouldhelpyouunderstandkidneyfailureandyourlong-termprognosis.Yournephrologistcanalsoeducateyouaboutnewtreatmentsandthelatestresearchthatmayultimatelyleadtoslowingtheprogressionofkidneydisease.

Theinformationyournephrologistshareswithyouduringyourfirstvisitdependsontheunderlyingcauseofyourkidneyfailure.Ifyouhavediabetesandexcreteproteininyoururine,yournephrologistwilladviseyoutocontrolyourbloodsugarandbloodpressurewithdietandmedications.Ifapplicable,yournephrologistwillrecommendthatyouloseweight,stopsmoking,andtakemeasurestoloweryourcholesterol.

IfyouhavePKD,youmaybenewlydiagnosedandintheearlystagesofthedisease,withonlyafewcystsinyourkidneys.Itcouldbemanyyearsbeforethereisaneedfordialysisoratransplant.Moreover,ifyouarenewlydiagnosedandinyourfifties,youmayneverneeddialysisortransplantation,especiallyifyouhaveonlyafewcysts.Thediscussionofdialysisandtransplantationvariesgreatly,dependingonmanyfactors.

ByStage3,however,youmayhavelosthalfofyourkidneyfunction.AtStage3,yournephrologistwillprobablyadviseyouthatyouwillneeddialysisoratransplantinthefuture.

Itisimportantthatyouunderstandthedifferencebetweenstabilityofkidneyfunctionandlevelofkidneyfunction.Forexample,yournephrologistmaybesatisfiedifyourcreatinineremainsat3.0.However,hemightnotalwaysremindyouthatyouhavelostmorethanhalfofyourkidneyfunction,andthatbeingstablewithpoorkidneyfunctionisnotnormal.GFRalmostneverimproves.Remember,yournephrologistwantstobereassuringatthesametimethathewantsyoutotakecareofyou.Ifithasbeenawhilesinceyoudiscussedyourprognosiswithyournephrologist,askhimtodiscussyourfuturewithyou.

ManagingtheConsequencesofKidneyFailureAsyoureadearlierinthischapter,youmayencounteranumberofconsequencesinvolvingotherorgansandprocessesinyourbodyasyourkidneyfunctiondeclines.Althoughtheseproblemscanbeworrisome,yournephrologistcanhelpyoumanagethem.

Kidneydiseaseisaprimaryriskfactorforheartdisease—includingheartattacks—justlikesmokingandhighcholesterolare.Asaresult,yournephrologistwillencourageyoutomanageyourbloodpressureandtoliveahealthylifestyle.Livingahealthylifestyleisoneaspectofyourcareoverwhichyouhavetotalcontrol.Youcanmanageyourdietmorethanalmostanyotheraspectofyourlife.Asyourkidneyslosetheirabilitytoworkproperly,eatingaheart-healthydietisessential—alongwithmanagingyourbloodpressureandloweringyourcholesterol.Ifyouareobese,loseweightandbeginanexerciseprogram.Ifyousmoketobacco,stopsmoking.Gethelpwithweightlossandsmokingcessationifyouneedto.

Dependingonthestageofkidneydisease,yournephrologistmayrecommendthatyoueatalow-saltdiet,especiallyifyouhavehighbloodpressure.Failingkidneyscannoteliminatetheexcesssaltintake,andsothesofttissuesofthebodybegintoaccumulatefluid.Thisaccumulatedfluid,callededema,canbeuncomfortable,especiallyifitcollectsinthelegsandankles.Fluidaccumulatinginthelungsrestrictstheairwayandcanimpairbreathing.Prescriptiondiureticscanhelpcontrolyouredemaaslongasyoucanstillpassadequateamountsofurine.Occasionallyexcessivefluidinthelungsisamedicalemergency,requiringhospitalizationforremoval.Tellyourdoctorimmediatelyifyouhaveanytroublebreathing.

Yournephrologistwillrecommendamodestrestrictionofproteininyourdiet,becausealower-proteindietmayslowtheprogressionofkidneydisease,especiallyifyouhaveproteininyoururine.Youshouldeataheart-healthy,high-fiber,low-fat,low-cholesteroldiet.Youcanfindmoreinformationaboutdietinchapter5.

Aswelearnedinchapter2,kidneysdomorethanjustfilterwasteproductsoutoftheblood.Kidneysalsocontrolbloodpressure,regulateredbloodcellproduction,maintaintheproperacidityintheblood,controlpotassiumandphosphatelevels,andactivatevitaminDtohelpbuildandmaintainstrongbones.Whenkidneyfunctiondeteriorates,complicationswiththefunctionsdescribedabove(anddescribedinmoredetailbelow)mayariseandmayrequiremedicaltreatment.

Anemia

Lowlevelsofredbloodcells,oranemia,isoneofthecomplicationsofchronickidneydisease.Askidneyfunctiondeclines,theamountofthehormoneerythropoietinavailabletoregulateredbloodcellproductiondecreases,leadingtoanemia.Peoplewithanemiafeeltired,evenwithadequatesleep.Synthetic,injectablehormonetreatmentslikeEpogen,Procrit,orAranesp(Darbepoetin)mayhelptreatanemia.Ahealthcareprovidercaninjectthemedicationforyouorteachyouhowtodoityourself.

Prescriptionhormonetreatmentforanemiaismosteffectiveforpeoplewithhematocritrangesfrom30to33.Ifyourhematocritismuchhigherthantheselevels,hormonetreatmentmaybeunsafe,potentiallycausingheartproblemsandbloodclots.Yournephrologistwillcarefullymonitoryourhematocrittodeterminewhetherhormonetreatmentisrightforyou.

BloodAcidity

Whenkidneyscannolongerregulatebloodacidity,acidbuildsup,causingacidosis.Ifyouhaveacidosis,yournephrologistwillprescribesodiumbicarbonate(bakingsoda),whichneutralizestheexcessacid.Youcanuseeitherregularbakingsodathatyoufindinthegrocerystore,sodiumbicarbonatetablets,orsodiumcitrateliquid,whichthebodyconvertsintobicarbonate.

HighPotassiumandPhosphate

Potassiumandphosphatelevelsinthebloodmayrisewithprogressingkidneydisease.HighpotassiumandphosphatelevelstypicallyoccuratStages4and5.Normalkidneysregulatetheamountofpotassiuminthebloodbyexcretingexcessamounts.Askidneyfunctiondeclines,however,thekidneysmaylosethisabilityandbloodpotassiumcanincrease,sometimestodangerouslevels.Ifhighenough,potassiumcancauseaheartattack.Althoughyoucanhelplowerpotassiumlevelsbymanagingyourdiet,insomecases,yourdoctormayprescribesodiumpolystyrenesulfonate(Kayexalate)oradiureticlikefurosemide(Lasix)totreatexcesspotassium.Adietitiancanhelpyouchoosetherightkindsoffoodstoavoidhighpotassiumlevels.Yournephrologistwillrecommendaconsultationwithadieticianifneeded.Mostdialysiscentershavedieticiansavailable.Phosphorusintheformofphosphateisimportantintheproductionofenergy

fromconsumedfood.However,thebodydoesnotuseallofthephosphateingestedandmustremovetheexcessamounts.Normally,thekidneysdothatjob.Askidneyfunctiondeteriorates,thekidneycannoteliminatetheexcess

phosphate,soitaccumulatesandlowerscalciumintheblood.Inpeopleonornearingthestartofdialysis(seechapters2and6),thesedepositscan,intheextreme,removecalciumfromthebonesandleadtoosteoporosis.Peoplewithhighphosphorusmayalsoexperienceitching.Peoplewithhighphosphoruslevelsmustreducephosphateintake(seechapter6)andmayneedtotakemedicationstobindingestedphosphatebeforeitcanbeabsorbed.Over-the-countercalciumcarbonatetabletslikeTumsorprescribeddrugslikecalciumacetate(Phos-Lo)andsevelamer(Renagel)canhelpcontrolhighphosphoruslevels.

LowVitaminD

Asyoulosekidneyfunction,yourbodymaynotmakeenoughkidney-activatedvitaminDtomaintainsufficientcalciumlevelstokeepyourbonesstrong.Inaddition,parathyroidhormonelevelscanrise,leachingcalciumoutofyourbones.Inreversetowhathappenswithexcessphosphateintheblood,inadequatelevelsofcalciumcanmakeyourbonesbrittle,causingthemtobreakmoreeasilyorbegintohurt.YournephrologistcantreatvitaminDdeficiencywithseveraldrugs,likeparicalcitol(Zemplar)orcalcitriol(Rocaltrol),syntheticformsthatbypasstheneedforyourkidneystoactivateinactiveformsofvitaminD(seechapter2).

TheSignsandSymptomsofFailingKidneysWhenourkidneysareworkingnormally,wemaybeunawareoftheirgreatabilitytocleanseourbodiesofthetoxinsthataccumulateafterwedigestourfood.Urinationistheonlyovertsignthatourkidneysworkatall.Andwhenourkidneysslowlybegintofail,wecandetect,atfirst,onlysubtlechangesinhowwefeel.Hereareafewofmyexperienceswithkidneyfailureandadescriptionofhowmynephrologisthelpedme.

Duringthefirstthreestagesofkidneydisease,Ifeltfine.TheonlyhealthissueIfacedduringthatperiodwashighbloodpressureandakidneyinfection.Myfirstsymptomofkidneyfailurewasfatigue.Myfatigueoccurredslowly,soinitiallyIdidnotnoticeanythingunusual.IjustassumedIwasworkingtoohardorwasnotgettingenoughsleep.Intime,fatiguebecamenoticeable.BythispointIhadreachedStage4kidneyfailure.

DuringthetwoorthreeyearsbeforeIbegandialysis,IwassotiredthatIhaddifficultygettingupforworkeverymorning,nomatterhowmuchsleepIgot.Finally,aftertellingmynephrologistaboutmyfatigue,testsshowedthatIhadbecomeveryanemic.Withfewerredbloodcellscarryingoxygenthroughoutmybody,mymusclescouldnolongerdowhattheyneededtodoforverylong

body,mymusclescouldnolongerdowhattheyneededtodoforverylongwithoutmyfeelingdebilitated.

Myredbloodcellcountwasverylow,becauseIhadlostsomuchofmyownerythropoietin(EPO).Asaresult,mynephrologistprescribedaninjectableformofthehormonetoproducemoreredbloodcells.Injectingitintomyownbodywassimilartowhatpeoplewithdiabetesdo—injectingthemselveswithinsulintonormalizetheirbloodsugar.Withpractice,IfounditeasytoinjectmyselfwithEPO.Besides,Ihadtodoitonlyonceaweek,ratherthanthetwice-a-dayinjectionsofinsulin.Afterseveralweeksofinjections,Istartedfeelingnormalagain.Intheend,thefatigueIexperiencedconfirmedwhatmyincreasingcreatininelevelswerealreadytellingme:mykidneyswerefailinganddialysisortransplantationwasinevitable.

Ayearlater,myfatiguereturnedandIbegantofeelincreasinglynauseatedandwasvomitingfrequently.Bythen,IwasapproachingStage5.NauseaandvomitingweretheworstsymptomsthatIhad.Tohelp,mydoctorprescribedondansetron(Zofran),whichisusedtotreatnauseaandvomitinginpeoplewithcancerwhoarereceivingchemotherapyorradiationtreatments.Eventhisheavy-dutydrugcouldnotcompletelytreatmysymptoms.IhadtotoughitoutuntilIcouldstartdialysisorreceiveatransplant.

Inadditiontonauseaandvomiting,IneededmoreEPOtokeepmyanemiaundercontrol.Moreover,Irequiredadditionalmedicationtocontrolmybloodpressure.Allofthisattentiontotreatmentcombinedwithsymptomssappedmyenergy,makingitdifficultformetodoanything.Asmykidneyfailureaccelerated,Ihadtodecide,withthehelpofmynephrologist,whenIwouldstartdialysis,becauseIdidnothaveakidneydonor.

Thedecisionwhethertostartdialysisortoreceiveakidneytransplant,ifadonorkidneyisavailable,isbothamedicalandapersonaldecision.Medically,peopleusuallycannotstartdialysisuntiltheirGFRisbelow15.MedicarewillnotpayfordialysisortransplantationuntilGFRis15orless,exceptwhenyourdoctorhasdocumentedotherreasons,likefluidoverload,highpotassium,oracidosisthatcannotbecorrectedwithfluidrestrictionormedications.

Forme,thedecisiontostartdialysisdependedmostlyonhowbadlyIfeltandonknowingthatdialysiswouldrequireasignificantchangeinmylifestyle.Italkedtosomepeoplewhothoughttheyhadwaitedtoolong.Althoughitcantakesometime,manypeoplefeelbetterafterstartingdialysis.Thedecisiontogetatransplantisusuallyaneasyone,unlessyouarenotmedicallyfitforone.Whenmykidneysfailed,Ireallyhadnochoice.IhadtodosomethingifIwantedtocontinueliving.WhenIfinallyfacedthatdecision,Istarteddialysis.

wantedtocontinueliving.WhenIfinallyfacedthatdecision,Istarteddialysis.Asitturnedout,itwasnottheendoftheworld.Itsavedmylife.

Idonottellmystorytoscareyoubuttomakethepointthattherearemanywaystominimizetheconsequencesofkidneydisease.Youshouldlearnhowtopreventorslowtheprogressionofyourdecliningkidneyfunction.Thisknowledgecanextendyourhealthytimebeforeyouhavetomakelife-alteringdecisionsaboutdialysisortransplantation.Chapter5exploresthevariouswaysyoucanchangeyourbehaviorandvarioustreatmentstokeepyourkidneysworkingaslongaspossible.

5PREVENTINGANDPOSTPONINGKIDNEY

FAILURE

BenjaminFranklinwrotethatan“ounceofpreventionisworthapoundofcure.”Thisadageiscertainlytruewithkidneyfailure.Inchapter3welearnedthatthemajorcausesofkidneyfailure—diabetesandhypertension—canbeprevented.Evenaninheriteddiseaselikepolycystickidneydisease(PKD)hasenvironmentalandlifestylecomponents,whereinterventionscansometimesextendkidneyfunction,indefinitelyinsomecases.Whowouldnotwanttopreventtheirkidneysfromfailing?Certainly,fewofuswouldintentionallyliveourlivesinawaythatmightcausekidneyfailure.Manyotherwiserationalpeople,however,findithardtodowhatisbestfortheirhealthratherthanwhattheyareusedtodoing—orwhattheywouldprefertodo.Beyondhumannature,thereareseveralotherfactorsthatmightcircumventearlyinterventionsthatmightpreventordelaykidneyfailure.

Oneofthemisnotknowingthatyouaresick.Whenweareyoungandhealthy,it’seasytoneglectourhealth.Mostyoungpeoplehavenomedicalproblemstheyknowabout,eventhoughtheymaybevaguelyawareofsomethatmaylurkinthebackground.Thatwastrueformeinmylatetwenties.AfterIearnedmydoctorate,IpursuedaresearchcareerasavisitingfellowattheNationalInstitutesofHealth.Myfellowshipdidnotprovidehealthinsurance,andIcouldnotaffordtobuyit.BecauseIwashealthyatthetimeanddidnotknowIhadPKD,Itookthechanceofdoingwithouthealthinsuranceformytwo-yearfellowship.AsayoungmanIthoughtIwasinvincible—thatis,untilIdevelopedhypertensioninmythirties.Eventhen,Itookprescribedmedicationsandwentonwithmylife.

Evenwhenthewarningsignsofimpendingdiseaseappear,itcanstillbedifficulttobelievethatwemayeventuallyfaceaserioushealthconditionlikekidneyfailure.Denialmaypreventusfromtakingimmediateactionforourmedicalcondition,especiallyifweassumethattheconditionisnotseriousorthatwehaveplentyoftimetoaddressit(seechapter1).Mostpeoplewouldprefertofocustheirattentiononmoreimmediateissues.Oftenittakesamedicalcrisistowakeusup.

Ifweacceptthatweareatriskofaseriousmedicalproblem,shouldn’twewanttoconfrontit?Notnecessarily,becauseconfrontingmedicalconditionsisdifficult.Nevertheless,thefirststepinpreventingmoreseriouscomplicationsdowntheroadistoreachthestagewhereweacceptthatactingnowcouldsaveourlives.

Weunderstandenoughabouttheriskfactorsforkidneyfailurethatweknowsomethingswecandotosignificantlyreducethechancesofkidneyfailurebeforeitoccurs.Beingeducatedabouthealthrisksisagoodstart(seechapter3).InthischapterIoutlinesomespecificwaystoaddresstheserisks.Soundmedicalpracticesmayreducetheriskofkidneyfailureandaddressmanyotherhealthissues,liketheharmfulconsequencesofdiabetes,hypertension,andheartdisease.Inadditiontosafeguardingyourhealthonyourown,youandeveryoneelseneedtohaveregularmedicalcheckupsandtreatmentforanyunderlyingcausesofkidneyfailure.

WeightLoss,Diet,andExerciseHypertensionisoneofthemaincontributorstokidneyfailure,nomatterwhattheprimarycauseofkidneydecline.Althoughfactorsrelatedtodiabetes,glomerulardiseases,andPKDcandestroykidneyfunction,hypertensioncanacceleratethedecline.Amajorcontributortohypertensionisobesity.

Obesitycanincreasebloodpressureinseveralways.Forone,theheartmustworkhardertomovebloodthroughalargebody.Inaddition,therenin-angiotensinandadrenalinesystemsbecomeoveractive(seechapter2).Inpeoplewithdiabetes,insulinresistanceisafactor.Fatdepositscanapplypressureontheoutsidewallsofbloodvessels,increasingresistancetobloodflow.Finally,increasedsaltconsumptionaccompaniesovereating;excesssaltintakepromoteswaterretention,furthercontributingtohypertension.Thebottomline?Overweightpeopleatriskofkidneyfailuremustloseweight.

Granted,losingweightiseasiersaidthandone.Booksandmagazinestoutvariouswaystoshedunwantedpounds,andIamnotgoingtoevaluatetheirclaims.Iwillconfirmthemantraofeveryweight-reducingdiet,however:toloseweight,youmustburnmorecaloriesthanyouconsume.Thismeansadoptingahealthy,low-calorie,low-fatdietandanexerciseprogram.

Iwasonceobese.Inmyearlyforties,Ibecametoofondofjunkfood.Overtime,Igained60to70poundsabovemyidealweight.Ihadapoorself-image,butwhatgotmyattentionwasanincidentoneeveningasIclimbedaflightofstairstobed.IfeltsowindedthatIcouldbarelybreathe.IrealizedthenthatifI

didnotdosomethingaboutmyweight,Imightnotmakeittomysixties.Inconsultationwithmyphysician,Ichangedmydietandstartedexercising.

Changingmydiettooktime.MybodyhadbecomeaccustomedtoallthesugarandfatthatIhadbeeneating.Eventuallymynewdietstuck,andIreachedapointwhereeatingjunkfoodmademesick.Stickingtomydietdidn’tmeanIhadtodeprivemyselfofanything.WhenIhadacravingforacertainfood,Iwouldletmyselfeatit,butonlyverysmallportions.Allowingmyselfthisluxuryhelpedmeavoidconsumingextracalories.

Beginninganexerciseregimenwasalsoachallenge,largelybecauseIdidnotknowhowtodoiteffectively.SoIhiredapersonaltrainerwhoacceptednoexcusesfrommeaboutnotcomingtothegymasscheduled.Thefirstfewmonthswereveryfrustrating.Ididnotloseanyweightatallforthreemonths,eventhoughIatealow-caloriedietandvigorouslyexercised.Ittookthatlongtotrickmybodyintoacceptingmylowercaloricintakeinsteadofmyusualhighcaloricconsumption.Afterthat,Ilost30poundsinafewmonths.Eventually,Ilosttheextrapoundsandreturnedtoanormalweight.

Iknowfirsthandhowdifficultitistoloseweight.Therearenoquicktricks,either.Toloseweightandkeepitoffrequiresapermanentchangeinlifestyle,involvingdietandexercise.Youmustmakelosingweightapriorityandyoumustbemotivated,disciplined,anddeterminedtogettoahealthyweight.Withthehelpofyourdoctor,anutritionist,perhapsapersonaltrainer,andthesupportoffriendsandfamily,you,too,canloseweight.Ittakesalong-termcommitmentandpatience.

Salt,Protein,andPhosphorusRestrictionReducingyourintakeofspecificfoodsmayhelpyouloseweightandmayalsoreducethestrainonyourkidneysandprolongtheirfunction.

Thefirstdietarychangethatpeoplewithkidneydiseaseshouldmakeistorestrictsaltintake.Mostnutritionistsrecommendthatyouingestnomorethan2,000to2,400mgofsalteachdayfromallsources.Butsomuchofwhatwebuyandeatisloadedwithsaltthatsaltcanbedifficulttoavoid.Eatinglesssaltcanbehardtogetusedto.Likeeatingfewercalories,youcanconditionyourselftopreferthetasteoffoodswithlesssalt.Thebiggestculpritsprovidingexcesssaltaremealsinrestaurantsandpreparedfoods.

Restaurantsoftenserveextremelylargeportionsoffood.Restaurantmealsarealsooftenexcessivelysalty.Whileyoushouldn’tavoideatinginrestaurants,therearewaysyoucanminimizeyourcaloricandsaltintake.First,ifyourmealistoolarge,divideitinhalforinthirdsandtaketheresthomeforsubsequent

istoolarge,divideitinhalforinthirdsandtaketheresthomeforsubsequentmeals.Avoidorderingmenuitemsthatcomewithsauces,whichareoftenfulloffatandsalt.Youmayalsoaskthecheftoavoidsaltingyourfoodasmuchaspossible.(Youcanalwaysaddsomesalttotasteifthefoodistoobland.)Eatgrilledorbroiledfoodinsteadoffriedfood,whichisgenerallyhighinfat.(Ifthegrilledorbroiledfoodiscoatedwithfatandsalt,however,itmaystillbeunhealthy.)Finally,experimentwithhealthycuisinesthatyoumaynotnormallyeat.Youmaydiscoverfoodsthatyoureallylikeandthataremorenutritiousandlesssaltythanyournormalfare.

Preparedfoodsoftenhavetoomuchsalt.Thisisespeciallytrueoffrozenmealsandcannedfoodsandsoups.Youdon’tneedtoavoidtheseconveniencefoodscompletely,butlearnhowtoreadthenutritionlabels.Ifyounormallyeatthreemealsaday,rememberthatasinglemealcannotcontainmorethan670mgofsaltandstillremainwithinthedailyguideline.Ofcourse,ifyoueatmorethanthreemealsaday—apracticethatisoftenrecommendedindieting—eachsmallmealmusthaveproportionallylesssalt.Severalcompanies,likeHealthyChoiceandLeanCuisine,sellfrozenmealswithlowersaltcontentthanothercompanies’products.Readandcomparelabels.Cannedfoodsoftenhavealotofsalt,butyoucansignificantlyreducethesaltcountbydiscardinganyliquidinthecansandbyrinsingthecontents.Obviously,thisapproachwillnotworkwithcannedsoups,whichgenerallyshouldbeavoided.Ifyoulikesoup,makeyourownwithfreshingredientsandaslittlesaltaspossible.

Reducingproteininthedietmayalsobehelpfulinpostponingkidneyfailure,assuggestedbyconsiderableevidenceobtainedfromanimalstudies.Becausekidneysnormallyfilterproteinandreturnittotheblood,withlowerlevelsofprotein,theydonotneedtoworkashard.Peoplewithdiabetesorglomerulardiseases(whereproteinspillsintotheurine,reflectingkidneydamage)canimprovetheirhealthbyeatinglessprotein.Inaddition,youmighteatsoyorotherplantprotein,likelegumesandwholegrains,ratherthananimalprotein.Althoughresearchershavenotextensivelystudiedproteinintakelevelsinhumans,reducingtheamountofproteinyouconsumehaslittledownsideriskandmightbebeneficialtoyourhealth.Peoplewithadvancedkidneyfailureshouldexercisecaution,however.Reducingyourproteinintakemayresultininsufficientcaloricintakeandmayputyouatsignificantriskofmalnutrition.Talktoyournephrologistandyourdietitiantostriketherightbalance.

Aswelearnedinchapter2,phosphorusintheformofphosphateisanimportantelementinmanyenergy-producingreactionsofthebody.Becauseweconsumemorephosphorusthanweneed,thekidneymustexcretetheexcess

amount.Limitingphosphorusintakecanhelptaketheloadoffyourkidneys.Whenaperson’skidneyfunctionispoororthepersonisondialysis(seechapter6),itisevenmoreimportanttolimitphosphorusconsumption.Coladrinksanddairyproductsareamainsourceofphosphorusandmayhavetobeconsumedinsmallamountsonly.Ricemilkisasuitablesubstituteforskimmilk.Soymilkcontainstoomuchphosphorus.

ReadingFoodLabelsIt’seasytoeatthewrongfoods,inpartbecausewedonotunderstandwhat’sinthefoodwe’reeating.Learntoreadafoodlabelasonewaytohelpavoideatingharmfulfoods.Figure5.1showsanexampleofatypicalfoodlabel—forpackagedmacaroniandcheese.Severalitemsonthelabelareparticularlypertinentforpeoplewithfailingkidneysaswellasforpeopletryingtoloseweight.

First,checktheservingsize.Itcanbeeasytobuyanitemthatlooksasifitisasingleservingwhenitisnot.Asmallpackageofsnacksorbottleofsodarepresentsmorethanoneserving.Asfigure5.1shows,eatingtheentireitemmeansconsumingtwoservingsanddoublethecalories,fat,andsaltofthesingleservingasgaugedbythefoodmanufacturer.

Ifyouarelimitingfatintake,checkthenumberofcaloriescontributedbyfat,whichislistednexttothenumberoftotalcaloriesperserving.Considerthatthelabelindicatesthatasingleservingcontains110caloriesfromfat,whilethereare250totalcaloriesinthesingleserving.Thismeansthatalmost50percentofthecaloriesinasingleservingcomesfromfat!Andthepercentageisoftenmuchhigherforcheesesandcookingoils,sopeoplewhoconsumealotofthesefoodsaretakinginmorefatandcaloriesthantheymightrealize.Checkthelabels.Lookforfoodwherethemajorityofthecaloriescomefromasourceotherthanfat.

Figure5.1.ATypicalFoodLabel

Fat,cholesterol,andsodium—thesubstanceslabeled“LimitTheseNutrients”infigure5.1—shouldbeconsumedonlyinsmallamountsifyouhavekidneydisease.Ahigh-fatandhigh-saltdietcanleadtotheformationoffatdepositsinbloodvesselsandtohighbloodpressure,heartdisease,andsomecancers.Somefats,however—thosedesignatedasmonounsaturatedorpolyunsaturated,likeoliveoil—maybebeneficial.Thenutrientslabeled“GetEnough”arehealthyandshouldbeconsumedinlargeamounts.Somepeopledonotgetenoughvitaminsandmineralsintheirdietsandmayneedtotakesupplementstosatisfytheirdailyrequirements.

Thefootnoteatthebottomofafoodlabelprovidesbasicnutritionalinformation,basedontheadviceofexperts,ontheupperandlowerlimitsyoushouldconsumedaily,dependingonthenumberofcaloriesconsumed.Values

shouldconsumedaily,dependingonthenumberofcaloriesconsumed.Valuesforfat,cholesterol,andsodiumrepresenttheupperlimit,whereasthedietaryvalueforfiberistheminimumdailyamountmostpeopleneed.Basedonthoseguidelines,thepercentageofthedailyvaluesprovidedbythefood(inthiscase,thepackagedmacaroniandcheese)islistedbyeachitem.Avalueof5percentorlessislow,whereas20percentormoreishigh.Thesevaluesprovidecomparisonsamongfooditemssoit’seasiertoidentifywhichfoodsarebestforyourdiet.

Unfortunately,foodmanufacturersarenotrequiredtolistthepotassiumorphosphoruscontentperservingontheirfoodlabels.Thisposesauniquechallengeforpeoplewithkidneydisease.Somemanufacturerslistthemvoluntarily,helpingyoutoknowwhichproductsaresafetoeatandwhichitemsaretobeavoided.Chapter6listssomefoodsthatarehighandlowinpotassiumandphosphorus.

ManagingYourBloodPressureAlthoughobesitycancontributetohypertension,noteveryonewithhypertensionisoverweight.Inobesepeopleandinpeoplewithhypertension,however,dietalonemaynotlowerbloodpressuretothedesirable120/80orbelow.Somepeoplemusttakemedicationstocontrolhighbloodpressure.

Recentresearchsuggeststhatmaintainingabloodpressureof125/75canpostponekidneyfailureforyears.Luckily,thetreatmentofhypertensionhasevolvedoverthelastfourdecades,andtodaytherearemanyclassesofmedicationsworkingthroughdifferentmechanismstocontrolbloodpressure.Althoughasinglemedicationmaybeeffectiveincontrollinghypertension,clinicalresearchhasshownthatacombinationofmedicationsmaybeneededtoreducehighbloodpressure.Workingthroughdifferentmechanisms,someclassesofmedicationsmaybebetterthanothersinprotectingkidneyfunction.

Inchapter2,Idiscussedabiochemicalprocessinitiallymediatedbythekidneythatcancausehypertension.Thisprocessinvolvesthereleaseofthehormonereninfromthekidney.Reninactivatesangiotensinsyntheticpathways,wherebyangiotensinIIconstrictsbloodvesselsandincreasesbloodpressure.

TherearetwowaystointerferewiththeabilityofangiotensinIItoelevatebloodpressure:blocktheproductionofangiotensinIIorreducetheactionsofangiotensinIIonbloodvessels.MedicationsthatblocktheformationofangiotensinIIarecalledangiotensin-convertingenzyme,orACE,inhibitors.Onesuchmedicationislisinopril(ZestrilandPrinivil).Thesedrugshavebeeninuseformanyyears,havebeenwellstudied,andmightbeespeciallybeneficialin

protectingkidneyfunction.AnotherdrugthatblocksangiotensinIIreceptorsislosartan(Cozaar).Thisdrugalsoreducesbloodpressureeffectively.Becauseoneofthesedrugclassesmaynotbesufficienttolowerbloodpressuretothedesiredlevel,theeffectivenessofcombiningbothclassesofdrugsiscurrentlyunderinvestigationfortreatingPKD.

Theotherdrugclassesthatcanreducebloodpressuredosodirectlybyrelaxingbloodvesselsoralteringheartrateandtheamountofbloodtheheartejectswitheachbeat(cardiacoutput)—orthroughacombinationoftheseeffects.Atthecellularlevel,allofthesedrugsworkbyblockingreceptorsthatnormallytranslatethesignalsofthebody’shormonesorchemicaltransmittersintoaphysiologicalresponse.Twoclassesofdrugsthatlowerbloodpressureactontheheartand,tosomeextent,onthebloodvesselsdirectly.Oneclass,namedbeta-blockers,slowstheheartrateandreducescardiacoutput,therebylesseningtheburdenontheheartandreducingbloodpressure.Atenolol(Tenormin)isacommonlyprescribedbeta-blocker.Theotherclassofdrugsactingontheheartandbloodvesselsincludesthecalcium-channelblockers.Thesedrugspreventtheinflowofcalciumintocellsthatstimulatethecontractionofmuscleintheheartandbloodvessels,therebyloweringbloodpressure.

Aswelearnedearlier,hypertensionisoftendifficulttotreatwithonlyoneclassofdrug.Tocontrolyourhypertension,youmayneedtotakeseveraldifferentclassesofdrugswithdifferentactions,andpossiblyothersaswell,including,forexample,diuretics(waterpills)likehydrochlorothiazide(Microzide);alpha-blockersliketerazosin(Hytrin),whichactsdirectlyonthebloodvessels,orothers,whichworkthroughthebrain;andminoxidil(Loniten),whichdirectlyopensbloodvessels.Yourdoctormaydeterminethebesttreatmentforyourhypertensionbytrialanderror.

ExperimentalMedicationsandClinicalTrialsPreventingkidneyfailuredependsoneffectivelytreatingtheunderlyingcausesofkidneyfailure.Therearemanywaystotreathypertensioninapersonwhohasnootherunderlyingdiseases.However,therearenotasmanywaystotreatdiabetes,glomerulardiseases,andPKD.Clinicalresearchersarealwaysworkingtodevelopnew,moreeffectivedrugs.Theydothisbyfirststudyingrelevantmechanismsinanimaltrials.Iftheresultsarepromising,theymoveaheadtoclinicaltrialsusinghumanvolunteers.Thefederalgovernmenthasestablishedawebsitethatlistscurrentclinicaltrials:www.clinicaltrials.gov.Onthiswebsiteyoucanfindinformationaboutcurrentresearchandapplications.Therearesomepromisingnewapproachestotreatingtheunderlyingdiseasesthatcanlead

tokidneyfailure.Hereareafewexamplesofwhatclinicalresearchersarepursuing.(Whenreadingthesedescriptions,keepinmindthat,inscientificandmedicalresearch,newtreatmentpossibilitiesemergewhileothersbecomedeadends.)

Diabetes

Thefirstlineoftreatmentfordiabetesiscontrollingglucoseandinsulinlevels.Forpeoplewithmilddiabetes,ahealthydietisthefirststep.Thebody’ssupplyofglucoseandinsulinisfurtherregulatedthroughmedicationsthataretakenorally.PeoplewithType1diabetestakeinsulineitherintramuscularly(asaninjectionintomuscletissue)orsubcutaneously(byusinganinfusionpumpundertheskinthatcontinuouslyreleasesinsulin).Noneofthesetreatmentsisacurefordiabetes;clinicaltrialsareunderwaytofindbettertreatmentsoracureforbothType1andType2diabetes.

Researchersareworkingtodevelopbetterdrugsthatcancontrolcellularresponsivenesstoinsulin.PeoplewithType2diabetesareinsulinresistantandmaybenefitfromoralmedicationsthatimproveinsulinresponsiveness.Insulinresponsivenessisaprimetargetforresearch.Althoughthesetypesofdrugshavebeenavailablefordecades,theyhavenotbeenveryeffectiveinpeoplewithseverediabetes.Forthesepeople,insulininjectionsareneededtocontrolbloodglucoselevels.Futuredrugsmaybemoreeffectiveincontrollinginsulinresistance,meaningthatmorepeoplewithdiabetescaneliminateorpostponetheneedtotakeinsulin.Inthelongterm,thesedrugsmayreducethenumberofpeoplewithdiabetesexperiencingkidneyfailure.

ClinicalstudiesonType1diabetesarelookingforbettertreatmentoptionstoprotecttheinsulin-producingbetacellsfrombeingdestroyedbythebody’sownantibodies.Thecurrenttreatmentapproachofsuppressingtheimmunesystem,whichinterfereswithallimmunereactions,makespeoplemorevulnerabletoinfections.Thegoalofthelatestresearchistofindspecificpathwaysintheimmuneresponsethatattackbetacellsratherthantheimmunesystemasawhole.Researchisslowlyidentifyingthepathwaystothebesttargetsfortherapeuticinterventionaswellaseffectivenewmedications.

AnotherwaytotreatType1diabetesistodesensitizethespecificimmuneresponsethatdamagesbetacells,sothatthepathwayislessresponsivetoautoimmuneattack.Desensitizingtheimmuneresponsealsoreducesthechancethatatransplantedorganwillberejectedbythebody.IparticipatedinsuchaclinicaltrialwhenIreceivedmykidneytransplant(seechapter7).Inislettransplants,pancreaticisletcellsfromdeceaseddonorsareinfusedintoapatient

torestoreinsulinsecretionwithoutthepatientneedingtousesteroidstosuppresssystem-wideimmuneresponses.

GlomerularDiseases

Newtreatmentsforglomerulardiseasesareemerging,too.Theapproachofthesetreatmentsvariesdependingontheoriginalsourceofthedisease(seechapter3).Glomerulardiseasesareinflammatorydiseasesthatleadtoscarringoftheglomerulus,andmostofthetreatmentoptionsreducethisinflammationusingsteroids.Mostclinicaltrialsoninflammationfocusoninflammatorydiseaseslikelupus.Here,similartothestudiesofType1diabetes,researchersareexaminingpathwayswithintheimmunesystemtofindthemostselectiveapproachtominimizeorslowthescarring,withoutusingsteroids.

Oneclinicaltrialistestingadrugthatreducesscarformation.Unlikedrugsthatsuppresstheimmunesystem,thisdrug(pirfenidone)actsbyblockingthedevelopmentofscartissue.Thegoalistopreventfurtherscarringinpeoplewithdecliningkidneyfunction.

PolycysticKidneyDisease

ClinicaltrialstofindmedicationstoretardcystgrowthinPKDpatientsarepursuingwhatisperhapsthemostpromisingapproachfortreatingamajorcauseofkidneyfailure.Havingdevelopedabetterunderstandingoftheunderlyingmechanismsofhowcystsforminthekidneys,researchershavebeenlookingforwaystoshrinkthesizeofthecysts.Inadditiontoamulti-centertrialcombiningdrugsthatactontheangiotensinsystem,asdiscussedearlier,otherstudiesaretakingadditionalapproaches.

Themostadvancedoftheseclinicaltrialsinvolvesblockingtheactionofthehormonevasopressin.Vasopressin,whichisreleasedfromthepituitaryglandtoconservefluidinthebody,doessobystimulatingcellularmechanismsthatcancausecystformationandgrowthinpeoplewithmutationsintheirPKDgenes(seechapter3).Indeed,vasopressinlevelsarehigherinPKDpatients.AninhibitorofvasopressincanretardcystformationinamousemodelofPKD.Tolvaptan,aninhibitorofvasopressin,iscurrentlyinPhaseIIIclinicaltrialstodeterminehoweffectiveandsafeitisintreatingPKD.

Otherdrugsarebeingdevelopedtoinhibitthesizeandnumberofcystsbyblockingtheirbloodsupply,withoutwhichtheydie.Asimilarstrategyhasbeensuccessfulfortreatingsometypesofcancer.Onestudyusesadrugcalledsirolimustosuppresstheimmunesysteminpeoplereceivingorgantransplants.ResearchersfoundthatPKDkidneysandliversshrankaftertransplantin

patientstakingsirolimus,unlikewhathappenswhensuchpatientstakeotherimmunosuppressants.Ifthisdrugworksinblockingcystformationandgrowthinhumans,itcouldhelpwiththedevelopmentofnewdrugswithoutanimmunosuppressanteffect.

Newresearchontheunderlyingcausesofkidneyfailureandthedevelopmentofpotentialtreatmentsofferhopetopeopleinfearoflosingtheirkidneyfunctionandoffacingdialysisortransplantation.Someday,wehope,therewillbenoneedfordialysisclinicsandtransplantlistsandlessneedforexpensiveandinvasivemedicalinterventions.Inthefuture,thelivesofmanypeoplewithkidneydiseaseswillimprove.

Inthemeantime,peopleapproachingkidneyfailuremustexaminethechoicesavailabletoreplacetheirimpendingkidneyfailure.Chapters6and7coverwhatyoucanexpectwithdialysisandtransplantation,andintroducesomecopingskillsthatIfoundhelpful.

6DIALYSIS

Untilrecentdecades,fewseriouslyillpeoplegotasecondchanceatlife.Itwasn’tuntilthetwentiethcenturythateffectivetreatmentsweredevelopedformanydiseases.Now,antibioticsandothermedicalinterventionsroutinelypreservelifeformanywhomightotherwisedie.Likepeoplewithseriousinfectionsandpeoplewithcancer,peoplewithkidneyfailurearenowhavingmuchlongerlifeexpectanciesthantheywouldhavehadinthepast.Inthepast,thekidneysofpeoplewithkidneyfailuredeterioratedtothepointwhereuremia,anexcessivebuildupoftoxinsintheblood,resultedindeath.

Today,however,therearetreatmentsforkidneyfailure,includingdialysis.Althoughtestedasearlyasthenineteenthcentury,dialyzingbloodtoreduceuremiaonlybecameausefultreatmentforchronickidneyfailureinthe1960s.NowdialysisisinuseallovertheUnitedStatesandisavailabletoanyonewhoneedsit.AccordingtothelateststatisticsfromtheNationalInstitutesofHealth,morethan381,000peoplewereonsomeformofdialysisattheendof2008.1

Therearetwoformsofdialysistotreatkidneyfailure:peritonealdialysisandhemodialysis.Bothformsofdialysismovetoxinsacrossabarrierthroughwhichonlysomesubstancescanpass.Thefollowingsectionexplainsthebasicconceptsofdialysis.

HowDialysisWorksDialysisinvolvesfiltration.Startwithabasicconcept:imagineatankofwaterintowhichyoucarefullyplaceadropofinkinonecornerofthetank.Theconcentratedinktendstodiffuseovertimethroughouttheentirecontainerofwateruntilitreachesthesameconcentrationinallpartsofthetank(figure6.1,top).

Nowinsertabarrier,throughwhichnothingcanpass,inthemiddleofthetank.Theinkdiffusesthroughoutonlyhalfthecontainer,asshowninfigure6.1(bottom).If,however,youpunchtinyholesintothebarrier,inkwillflowthroughthem—aslongastheinkmoleculesaresmallerthantheholes.Ifthemoleculesaresmaller,theydispersethroughouttheentirecontainerofwater(justlikeinfigure6.1,top).Iftheholesaretoosmallfortheinkmoleculestopassthrough,theinkremainsononesideofthebarrier(figure6.1,bottom).

Increasingthevolumeoftheleftsideofthetankcausestheinktodiffusefasterthroughthebarrieruntiltheconcentrationofinkisequalonbothsides,whiletheamountofinkisreducedontherightside(seefigure6.2).Forexample,ifyouplace3gramsofinkintherightsideofthetankwith1literofwaterandtheinkmovesthroughthebarriertotheothersidewith2litersofwater,theconcentrationofinkwilleventuallybeequalonbothsidesofthebarrier.Thismeansonly1gramremainsontheoriginalsideofthebarrier,andtheremaining2gramshavecrossedthebarrier.Thus,ontheoriginalside,theconcentrationofinkdeclinedfrom3g/lto1g/l,whileontheothersidetheconcentrationrosefrom0g/2lto2g/2l,or1g/l.(Figure6.2showstheamountofinkoneachsideofthebarrierratherthantheconcentrationofink.Becausetheconcentrationwouldbeequaloneachside,ifconcentrationswereillustrated,bothsideswouldbethesameshade,asinthetoppartoffigure6.1.)

Figure6.1.DialysisasFiltrationI.Withnobarriers,asubstancewilldiffuseuniformly(top).Ifabarrierisadded,diffusionwillonlyoccurinhalfthe

container(bottom).

Figure6.2.DialysisasFiltrationII.Thisfigureshowstheamountofinkoneachsideofthebarrierratherthantheconcentrationofink.

Sincetheconcentrationwouldbeequaloneachside,ifconcentrations(ratherthanamounts)ofinkwereillustrated,bothsideswouldbethesamecolor,asin

thetoppartoffigure6.1.

Thisconcept,calleddialysis,hasbeenusedforyearsbybiochemiststopurifychemicals.Similartotheinkanalogy,dialysisinvolvesasemi-permeablemembrane(abarrierwithholes)thatallowssomesubstancestopassthroughandnotothers,dependingonthesizeofthemoleculesinvolved.Toaccomplishthis,thechemicalneedingpurificationisplacedintoasmallsacmadeofthemembranousmaterial(thebarrierfromabove)throughwhichthesubstancetobepurifiedcannotpass.Next,thesacisplacedinavolumeofappropriatesolution

muchlargerthanthevolumeofsolutioninthesac.Theimpuritiesthatcanpassthroughthemembranewillflowuntiltheconcentrationisequalonbothsidesofthemembrane,butreducingtheiramountinsidethesac.Formaximumefficiency,thesolutionischangedfrequentlytoallowforthegreatestremovalofthecontaminantsinthesac.Whensuccessivelyrepeatingtheexchanges,nearlyalloftheimpuritieswilleventuallyberemoved.

Thisisthesamebasicapproachtofilteringthebloodofpeoplewithkidneyfailure.Earlystudiesinthe1940s,usingthisprincipleofdialysistocleanhumanblood,usedpigintestinesasthesemi-permeablemembrane,withthebloodpassingthroughtheinteriorpart.Theintestineswereplacedinbigwoodenvatsofsolutioncomposedofsaltsandbufferscompatiblewithblood.Otherlaboratoriestriedusingcellophane.Theideawastoremovethetoxinswithoutremovingcellsandimportantproteinsfromtheblood.Thisapproachprovedmoredifficultthansimplebiochemicaldialysis,butovertime,withfurtherrefinementsandminiaturizingtheprocess,themodernformsofdialysiswereborn.

Today,peritonealdialysisandhemodialysisarethemostcommonformsofdialysis.Hemodialysisismoreroutinelyused,butincreasingnumbersofpatientsarechoosingperitonealdialysisbecauseofitsadvantages.Therearedisadvantagestobothformsofdialysis,however;thesearecoveredindepthlaterinthischapter.

PeritonealDialysisTheprinciplesofperitonealdialysisremainthesameasdescribedabove,buttheapplicationisabitmorecomplicated.Likethebiochemicalapproachtodialysis,peritonealdialysistakesadvantageofthesemi-permeablemembranethatlinestheperitonealcavityoftheabdomen.Somesubstancescanpassthroughit,otherscannot.Tinybloodvesselsareembeddedinthisperitonealmembrane.Thebloodfromthebodyisanalogoustothecontentsofthemembranoussacdescribedabove.Asolution,calledthedialysate,isplacedintheabdomen,allowingthetoxinsinthebloodtoflowthroughtheperitonealmembraneintothesolution(seefigure6.3).Thisoccursbecausetheconcentrationoftoxinsinthebloodishigherthanitisinthedialysate(asinfigure6.2).Toavoidlossofneededsubstancesintheblood,thedialysatecontainssaltsandbuffersinconcentrationsequivalenttothosenormallyfoundintheblood,creatingequalconcentrationsofthesesubstancesonbothsidesofthemembrane.

Becausefluidbalanceiscompromisedinpeoplewithkidneyfailure,dialysismustalsoremoveexcesswaterfromthebody.Inperitonealdialysis,the

mustalsoremoveexcesswaterfromthebody.Inperitonealdialysis,thedialysatecontainsglucose(sugar)tohelpremovetheexcesswater.Becausetheconcentrationofglucoseexceedstheconcentrationinthebloodanddoesnotappreciablypassintothebody,excessfluidinthebloodflowsthroughtheperitonealmembraneintothedialysatetodilutetheglucose.Toremovemorefluid,higherconcentrationsofglucoseareneeded.Therateofdiffusionoftoxinsintothedialysatedeclineswithtime,sothedialysatemustbeexchangeduptofivetimesadayinordertomaximizetheremovalofthetoxins.

Beforeperitonealdialysiscanbeperformed,asurgeonmustplaceaspecialcatheterinsidetheabdominalwall(seefigure6.4).Thepartofthecatheterthatisinsidetheabdominalwalliseitherstraightorcurledlikeapig’stail,andhasholesinit,whereasontheoutsidethecatheterisstraight,solid,andflexibleandhasaholeonlyattheoutsidetip.Theholeintheabdomenthroughwhichthecatheterexitsisknownastheexitsite.Thesubcutaneousandperitonealcuffsholdthecatheterinplace,andaresewnintotheabdominalwall.Withperitonealdialysisitiscrucialtoavoidinfections,whichcanoccurbecauseeitherthecatheterortheexitsitebecomescontaminated.Afterthecatheterhasbeeninplaceforabouttwoweeks,dialysiscanbegin.Onceanexchangehasbeencompleted,asterilecapwithanantiseptic(likeBetadyne)ontheinsideisscrewedontotheoutsideendofthecatheter(ontheleftendsofthecathetersinfigure6.4)untilthenextexchange.

Figure6.3.DialysateFlowingintotheAbdomen

Figure6.4.StraightCatheter(top)andCurledCatheter(bottom)UsedforPeritonealDialysis

Asurgeonhasflexibilityonwheretoplacethecatheter.Unfortunately,IdidnottalkwithmysurgeonaboutplacementbecauseIdidnotknowthatIcould.Asaresult,whenIreceivedaperitonealcatheter,itwasplacedatmywaistline.Wearingpants,withthesubcutaneousandperitonealcuffsdirectlyundermybelt,wasveryuncomfortable.Talkwithyoursurgeonaboutwhatoptionsheorshecanprovideforcatheterplacementthatwillminimizediscomfort.

ContinuousAmbulatoryPeritonealDialysis(CAPD)

Toperformexchanges,youneedgoodmanualdexterity,buttherearedevicestohelppeoplewithphysicallimitations.Thereareevendevicesthathelpblindpeoplewithexchanges.

Peritonealdialysisistypicallybegunusingaprocedureknownascontinuous

ambulatoryperitonealdialysis(CAPD),inwhichdialysisoccursthroughoutthedaybetweenchangesofthedialysissolutions(calledexchanges).Exchangingsolutionsisrelativelysimple—itisaprocessthattakesabouttwentyminutes,onceyouareusedtoit.Whatfollowsisthedescriptionofatypicalprocedureforperformingexchangestogiveyouanideaofwhatisinvolved.2(Note:Thefollowingdescriptionisnotasubstituteforappropriatetrainingbyaqualifieddialysishealthcareprovider.Talktoyourdoctoraboutthebestwaytoperformyourexchanges.)Theexchangeprocessmustbesterile,soyoumustmakeeveryefforttoavoidcontamination.Handwashingwithantibacterialsoaporothersuitabledecontaminantisrequiredatcriticalstepsintheprocess.Youmayalsowanttodryyourhandswithafreshpapertowelratherthanaclothtowel,toreducepossiblecontaminationfromthesoiledcloth.Yourdialysiscentermayprovideyouwithanultravioletlamptosterilizetheconnectionsbetweenthetubingandyourcatheter.

Dialysisbagscontainsterilesolutionsandcomeinsealedouterbags.Afterwashingyourhands,youwillopentheouterbagandremoveitscontents.Bagsofdialysissolutionincludeanattacheddrainbag,collectivelyknownasaY-set(seefigure6.5).Beforestarting,warmthedialysissolutiontobodytemperature(easilydoneinamicrowaveoven).Warmsolutionwillhelppreventabdominalcramping.Attachthefluid-filledbagtoabagpole,andstartyourexchange.

Figure6.5.Y-SetUsedinDialysis

Afterwashingyourhandsanddryingthemwithapapertowel,removeanddiscardthecaponthecatheter.Then,attachthecathetertothesystem,whichhasatubetothedrainbagandonetothebagcontainingfreshdialysate.Beforeflowcanoccur,breaktwoseals—oneonthedialysisbagandoneattachedtothecatheter.Afterallowingsomedialysatetopassthroughthelinestoprimethesystem(seetheupperleftsideoffigure6.6),clampthelinetothedialysatebagandopenthecatheterlinetoallowdrainageofyourperitonealfluid(seetheupperrightsideoffigure6.6).

Oncedrainageiscomplete,unclampthelinetothedialysatebagtoallowflowofsomefreshsolutionintothedrainbagtoremovebubbles(seethelowerleftsideoffigure6.6),clampthetubetothedrainbag,andthenallowflowof

freshdialysateintoyourabdomen(seethelowerrightsideoffigure6.6).Becausetheforceofgravityhelpsthedialysatetoflowmoreeasily,hangthebagaboveyourhead.Whenthebagisempty,clampthetubefromthedialysatebagandwashyourhandsagain.Then,detachthecatheterfromtheexchangesystemandimmediatelyscrewafreshcapcontainingBetadyneonthecatheter.Finally,emptythedrainbagandthendiscardthewholesystem.Atthispoint,yourexchangeiscomplete.

Dialysisexchangescanbedonealmostanywhereyoucanfindprivacy.Avoiddoingexchangesinpublicbathroomsorotherplaceswheretheremightbecontamination.Itisalsobestnottohavepeopleinthesameroomwhileyouareexchanging—again,becauseoftheriskofcontamination.

Ifyouworkwhileonperitonealdialysis,youwillhavetofindawaytodoexchangesinanofficeorcomparableroom.Ifthereisadropceiling,youcanattachthedialysatebagstotheceilinggridwithanS-hook,likeaplantholder.Otherwise,youmayuseabagpole.Duringexchanges,youcancontinueworkingaslongasyouhaveprivacy.Tominimizethenumberofexchangesatwork,dothefirstoneassoonasyougetupinthemorningathome,onejustbeforelunchattheoffice,onejustbeforeleavingforhomeattheendoftheworkdayorwhenyoufirstgethome,andthelastonejustbeforegoingtobed.

Figure6.6.DialysisExchangewithPeritonealDialysis

Thisscenariomaynotworkforeveryone.Forexample,ifyoudonothaveyourownofficeoranothersuitableplacetoperformexchanges,youmaynotbeacandidateforCAPD.Continuouscyclicperitonealdialysismaybeabetteralternative.

ContinuousCyclicPeritonealDialysis(CCPD)

LikeCAPD,continuouscyclicperitonealdialysis(CCPD)canbeausefuloption.CCPDusesamachine,calledacycler,whichperformsexchangesduringthenightwhileyouareasleep(seefigure6.7).Themachine(manufacturedbyBaxterInternational,Inc.,inDeer-field,Illinois)consistsofseveralparts:(1)adialysisbagheater;(2)aperistalticpumpinsidethemachine;(3)aplacefora

cassette(behindthedoorinfigure6.8);and(4)acomputer(behindthecontrolpanelinfigure6.8)toruneverything.Thecassettecontrolstheflowoffluidfromdialysatebagstotheabdomenandchannelsuseddialysatetowaste.Allofthetubingattachedtothecassetteisneededfordialysis(seethedisposabledialysissetinfigure6.9).Thecassetteworkswiththeperistalticpumptorollthefluidsthroughthetubing.Thecomputerisprogrammedtodirectthefloweithertowasteorfromoneofthedialysisbags.

TherulesforuseofacycleraresimilartotherulesforCAPD,especiallywhenitcomestocleanliness.Withpracticeandtrainingonhowthemachineworksandhowtoavoidcontamination,youcansetupthecyclerforuseinabouttenminutes.First,placea5-literdialysisbagontopofthecyclerwheretheheaterislocated.Next,putthecassetteinitsreceptacleandattachthedrainline,routingittoadrain,likeatoilet,sink,orbathtub.Beforeattachingtheappropriatetubestothedialysisbags,washyourhandstoavoidcontaminatingthebagswhenyouinsertthetubes.Whenthecyclerhasfilledthetubingwithfluid,washyourhandsagain,removeanddiscardthecaponyourcatheter,andthenattachittothetubeatthefarleftoftheorganizer(seefigure6.9).

Figure6.7.CyclerUsedinContinuousCyclicPeritonealDialysis

Figure6.8.PartsoftheCycler

Figure6.9.OrganizerandTubingoftheCycler

Oncethecyclerisactivated,youcangotosleep.Whilesleeping,ifyouturnmorethanonceinsuccessioninthesamedirection,youmightbecomeentangled

inthetubingorcrimpthetube.Ifthishappens,analarmwillsoundtoawakenyou,andthecyclerwillstopitself,asasafetymeasure.Trainyourselftorollonlybackandforthwhenyouwanttochangeyoursleepingposition.

Whileyouareasleep,thecyclerdoesseveralexchangesasprogrammedonthecomputer,basedonyournephrologist’sprescription.Astheamountofdialysateinthebagontheheaterdeclines,thecomputerbeginspumpingdialysatefromtheotherbags,sothattheheatercanwarmthesolutionfromthosebagsbeforeuse.Afterwashingyourhandsthenextmorning,detachyourcatheterfromthecyclerandscrewonafreshcapcontainingBetadyne.Tocompletetheprocess,discardalltheplastictubingandthecassette.Thisprocessatfirstseemscomplicatedbutitbecomeslesssowithpractice.ThebiggestadvantageofCCPDisthatfewerexchangesareneededduringtheday,especiallyifyoustillhavesomeresidualkidneyfunction.

MonitoringtheEffectivenessofPeritonealDialysis

Dialysisisaprescribedtreatmentand,justlikewithotherprescriptions,itseffectivenessneedstobemonitored.Nephrologistsusetwomethodstodeterminehowefficientlyyourtreatmentremoveswastesfromyourblood.Onetestisthecreatinineandureaclearance.Thistestissimilartothetestyourdoctorrequestedtodetermineyourkidneyfunctionbeforeyourkidneysfailed(seechapter4).Tohavethetestnow,youwillcollectallofthedialysisbagsoveratwenty-four-hourperiodaswellasanyurineyoustillproduceinalargecontainer.Whenyoutakethespecimensinforanalysis,youwillbeaskedtoprovideabloodsampletodeterminehowmuchcreatinineandureawereremovedfromyourblood.

Anotherwaytomeasuretheefficacyofyourdialysistreatmentisthroughaperitonealequilibriumtest(PET).Inthistest,youwillbeaskedtoprovideasampleofdialysateathourlyintervalsforuptofourhours.Thedialysatewillbetested.Therateatwhichdialysisremovesureaandcreatininefromyourbloodandtheextenttowhichyourbodyabsorbssugarfromthedialysatewilltellyournephrologisthowmanyexchangesyouneedtomaximizetheeffectivenessoftreatment.Fromthistestyournephrologistcandetermineifyourperitonealmembraneisarapidtransporteroraslowtransporter.Ifitisarapidtransporter,yourbloodcanmoreeasilyabsorbglucosefromthedialysate.Thisfeaturecanmakeitdifficulttomaintainyourbloodsugarifyouhavediabetes;asaresult,apersonwithdiabetesneedsmorefrequentexchanges.Ifyourmembraneisaslowtransporter,however,youwouldbenefitfromfewerexchanges,withthedialysateremaininginyourabdomenforalongerperiod.

BothCAPDandCCPDofferagreatdealoffreedomcomparedtohemodialysis.However,peritonealdialysismaynotbeforeveryone.Manynephrologistsdonotofferperitonealdialysisasanoptionbecausesomeoftheirpatientshavedevelopedperitonitis(aninflammationoftheliningoftheabdomen)fromit.Butperitonealdialysisisworthconsideringifyouhavethedisciplinetokeepupwithalloftheexchangesandobservetheroutinesnecessarytomaintaintherequiredcleanliness.Yournephrologistwillhelpyouweightheprosandconsofperitonealdialysis(includingperitonitis,coveredlaterinthischapter)andwillhelpyoudecideifperitonealdialysisisrightforyou.

HemodialysisHemodialysisworksonaprinciplesimilartothatofperitonealdialysis,exceptthebloodiscycledoutsidethebodythroughaspecialfilter,calledadialyzer,byamachinethatisusuallylocatedinadialysiscenter(seefigure6.10).Unlikeperitonealdialysis,whichisacontinuousformofdialysis,hemodialysisisintermittent.Thus,fluid,toxins,andelectrolyteimbalancesbuildupbetweensessionsofhemodialysis,whichmeansthatthepatientmustrestrictfluidintakeandlimitsomefoods.Mostpatientsgotoacenterthreetimesaweek,witheachdialysissessiontypicallylastingthreetofourhours.

Figure6.10.DialyzerUsedinHemodialysis

Somedialysiscentersofferhomehemodialysis.Ifyouhavesomeonewhocanhelpyousetupthemachine,inserttheneedlesintoyourfistulaorgraft,andmonitoryoursession,homehemodialysismaybeanattractiveoption,especiallyifyoucannotscheduledialysisaroundworkorifyourcenterisnotopenlateintheday.Inadditiontoregularfour-hour,three-day-a-weeksessions,youmaybeacandidatefordailydialysis,whichwouldreducetheaccumulationoffluidandtoxinsbetweensessions.Homehemodialysissessionslasttwohourseachday,ortheycanbeperformedduringthenightwhileyousleep.Researchsuggeststhatdailyhemodialysismayprovideabetteroutcomethanthree-day-a-week,in-centersessions,sinceitisamorecontinuousformofhemodialysis.Anincreasingnumberofpatientsdialyzeathome,aslongastheirdialysiscentercanprovideadequateoversight.Todialyzeathome,youmusthaveapersonassistingyoueachtimeyoudialyze,tomonitorthetreatmentincaseyouexperiencebleedingoradropinbloodpressure.Ifyourcenteroffershomehemodialysis,consultyournephrologisttoseeifitisagoodchoiceforyou.

Thecoreofhemodialysisisthedialyzer,alsoknownasanartificialkidney.Thefilteriscomposedoftinyfilaments(semi-permeablemembranes)through

whichthebloodpasses(seefigure6.11).Thesefilamentsarebathedinacontinuouslyflowingdialysatecontainingsaltsandbuffersinconcentrationstoavoidexcessivelossofthesesubstancesfromtheblood.Thisprocessinhemodialysisisanalogoustothepresenceofdialysateintheabdomenwhenusingperitonealdialysis.Thebloodcellsandlargemoleculespassthroughthedialyzerandreturntothebody,whilethetoxinsflowfreelythroughtheporesinthefilamentsandwashaway.

Figure6.11.FilamentsComprisingtheFilteroftheDialyzer

VascularAccessesforDialysis

Ifyouaretoreceivehemodialysisonaregularbasis,yournephrologistorasurgeonmustperformasurgicalproceduretoaccessyourbloodsupply;bloodwillbedrawn,pumpedthroughthedialysismachineanddialyzer,andthenreturnedtoyourbody.Typically,anaccessisplacedwhentheestimatedGFRisbelow30.Withsufficientadvancenotice,mostpeoplecanhaveapermanentaccessplaced(seebelow).Initially,however,youmayneedasimple,temporarycatheterplacedinalargeveininyourupperchestorgroin.Therearetwotypesofdialysiscatheter:theuntunneled(abovetheskin)andthetunneled(belowthe

ofdialysiscatheter:theuntunneled(abovetheskin)andthetunneled(belowtheskin)cuffedcatheter.

Figure6.12.Tunneled,CuffedHemodialysisCatheter

Ifyouneeddialysisimmediately,youmaygetanuntunneledcatheterplacedthroughtherightinternaljugularveininyourneckintotherightatriumofyourheartorthroughthefemoralveininyourgroin.Yournephrologist,interventionalradiologist,orsurgeonwillperformtheprocedurewhileyouareunderlocalanesthesia.Youmayexperienceabrief,temporaryflutteringinyourheartifthetipofthecathetercontactsheartmuscleintheatrium.Untunneledcatheterscanbeusedonlyforafewdaystoafewweeks,becausetheytendtocomeloose,fallout,orbecomeinfected.

Tunneled,cuffedcathetersmaybeusedforafewweekstoafewmonths(seefigure6.12).Buriedundertheskin,thetunneledcatheterislargerandlongerthananuntunneledcatheterandislesslikelytobedislodged.Moreover,sealedagainstbacteria,itislesslikelytobecomeinfected.

Neitherofthesetemporarycatheterswillserveyouforthelongterm,however.Amorepermanentandstableaccessisneeded.Twotypesofaccessareused:thefistulaandthegraft.Forbothofthese,thedialysistechnicianwillinserttwoneedles,onetodrawbloodintothedialysistubing,andonetoreturntheblood.Bothofthemwillprovideamoreefficientdialysistreatmentthancatheters,becausethebloodcanbecleanedmorequickly.Planningforafistulaorgraftshouldbedoneearly,toprepareforthetimewhendialysiswillbeneeded.

needed.Tocreateafistula,asurgeonjoinsanarteryinanarmorgroindirectlytoa

vein(seefigure6.13).Thisprocedureisdonewhileyouareunderanesthesia.Oversixtoeightweeks,thepressureonthevesselincreases,thickeningthewall,andthenenlargingthevein,makingiteasierforadialysisnurseortechniciantoplacethelargeneedlesfordialysis.Thefistulaisthemostdesirableaccesstohave.Becausethefistulaiscreatedfromyourowntissues,itismoreresistanttoinfection,laststhelongest,andhastheleastnumberofcomplications,comparedtotheotheraccesses.

ThegraftisaGore-Textubethatasurgeonplacesundertheskin,attachingoneendofthetubetoanarteryinyourarmorgroinandtheotherendtoavein(seefigure6.14).Inthiswaytheprocedureislikethefistulaprocedure,andit,too,isdonewhileyouareunderanesthesia.Thegraftmaybeusedsoonerthanthefistula—generallyyoucanuseitafteratwo-weekrecoveryperiod.Graftsarenotasgoodasfistulasfordialysisandaremorelikelytobecomeinfectedthanfistulas.Theyareagoodsubstituteiftheveinsaretoosmallforcreatingafistula,however.

Figure6.13.FistulaJoininganArteryandaVein

Fistulasandgraftsuseneedleswithlargerinternaldiametersthancatheters,whichallowsthebloodtomovefasterthroughthedialyzer.Dialysisismoreefficientwhenbloodcanpassmanytimesthroughthedialyzerduringasession.However,insertingtheselargerneedlescanbepainful.Tohelpeasethepain,adialysisnurseortechniciancannumbtheinjectionsiteusingalocalanestheticpriortoinsertion.Inordertoavoidclottingoftheaccess,thetubing,andthedialyzer,heparin(abloodthinner)isinjectedintotheaccesstubing.Asaresult,youmayexperiencesomebleedingfromyouraccessafterdialysis.Thestaffinyourcentercanminimizebloodlossbyapplyingpressuretothesiteusingclamps.Somedialysiscentershavespecialbandagescontainingasubstancethathelpsclotblood.

Figure6.14.GraftJoininganArteryandaVein

MonitoringtheEffectivenessofHemodialysis

Aswithperitonealdialysis,nephrologistsmustdeterminehoweffectivehemodialysistreatmentsare.Nephrologistsusetwomeasuresforthispurpose:theureareductionrate(URR)andtheKt/V.FortheURR,thedialysistechniciandrawsabloodsamplefromaportonthedialysismachineatthebeginningandattheendofdialysistreatment,andsendsthebloodsamplestoalabtodeterminehowmuchureaisineachsample.TheURRisthencalculated.AgoodURRisatleast0.65,whichmeansthatthetreatmentisremovingatleast65percentofureafromtheblood.

Kt/Vprovidesthebestestimateoftheeffectivenessofyourdialysistreatment.“K”standsforureaclearanceduringdialysis,“t”fortime,and“V”forvolume.ThecalculationofKt/Vistootechnicaltodiscusshere.Sufficeittosaythat,unliketheURR,Kt/Vaccountsforwidevariationsinweightamongpatientsbydeterminingthevolumeofwaterinthebodyandthenutritionalstatus.Thus,theKt/Vprovidesamoreaccuratemeasureofeffectivenessofatreatment.GoodKt/Vvaluesareatleast1.2to1.4,buthighervaluesarenotmorebeneficial.UsingtheKt/V,anephrologistcanmodifyaprescriptiontomaximizetheefficiencyofadialysissessionandhelpyoufeelbetter.

maximizetheefficiencyofadialysissessionandhelpyoufeelbetter.Yournephrologisthasseveralwaystoimprovethequalityofyourtreatment.

Forexample,hecancontroltheflowrateofyourbloodthroughthedialyzer.Ifyouhaveafistulaorgraft,hecanincreaseyourflowratetoobtainmoredialysisforyourtimeatthecenter.Anotherwaytoimproveyourtreatmentistoincreasethetimeondialysis.Finally,yournephrologistcanorderalargerdialyzertoallowmorepurificationofbloodeachtimeitcyclesthrough.

MonitoringYourHealthWhetherusingperitonealdialysisorhemodialysis,yourhealthmustbemonitoredclosely.Yournephrologistwillassesswhetheryourdialysisprescriptionisoptimal,andshewillalsohelpyoustayashealthyaspossible,soyoucanfeelyourbestandparticipateinmanyofyourregularactivities.Yourlaboratorymeasuresprovideanopenwindowintoyourhealththatwillhelpyournephrologisttreatyouappropriately.

Aswelearnedbefore,someofthesemeasuresstillmustbemonitored.Forexample,urea(theBUNnumberonalabreport)andcreatininelevelsrevealhowwelldialysisiscleaningyourblood.Iftheselevelsaretoohigh,youmayneedtoadjustyourdiet,oryournephrologistmayneedtochangeyourmedications.Potassiumlevelsareimportantinregulatingheartbeat.Ifyourpotassiumbecomestoohigh,youcouldexperienceanirregularheartbeator,inextremecases,aheartblock,resultingfromaprofoundslowingoftheheartrate.Calcium,phosphorus,andparathyroidhormonelevelsreflectyourbonehealth.Ifphosphorousandparathyroidhormonelevelsaretoohigh,youmayhavetolimitfurtheryourphosphorus-richfoodsortakehigherdosesofphosphatebinders.Yournephrologistwillalsomonitoryourredbloodcellcountandironlevels.Ifyoubecomeanemic,youmayrequireironsupplementationorerythropoietininjections.

Thereareothermeasuresofyourhealth.Albuminisaproteinthatcanbeameasureofyournutritionalstatus.Ifalbuminlevelsinthebloodaretoolow,youwillneedtoeatmorecaloriesandprotein.Evenifyouareeatingtherecommendedamountsofprotein,youmustconsumesufficientcaloriesfromothersources,oryourbodywillbegintoburnproteinforfuel.Inaddition,yournephrologistwillassessyourliverfunctionasageneralhealthmeasureandtolookfortoxicityfromanyofthemedicationsthatyoutake.

Irecommendthatyoumonitorandunderstandallofyourlaboratoryresults.Yournephrologistordialysisnursecanteachyouthemeaningofexcessively

higherorlowervaluesandtellyouaboutanytreatmentchangesthatmightberequiredifthelaboratoryresultschange.Learnhowtomanageyourdiet,lifestyle,andcompliancetoyourdialysisregimen.Youmaywanttokeepcopiesoftheresultstohelpyougetasenseofwhatisoptimalforyou.Allofthesestepswillgiveyoumorecontroloveryourhealthandwell-being.

ProsandConsEachtypeofdialysishasadvantagesanddisadvantages.Talktoyournephrologistabouttheseprosandconstodecidewhichtypeisbestforyou.

PeritonealDialysis

Only8.2percentofpatientschooseorareabletouseperitonealdialysis.Themainadvantageofperitonealdialysisisindependence,becauseitdoesnotrequiretripstoadialysisunit.Peritonealdialysisworksbestifyouareaself-starter,disciplined,andphysicallyabletoperformthenecessarystepsinvolved.Peritonealdialysisisabettertreatmentthanhemodialysisforpeoplewithloworunstablebloodpressure(whichcanmakehemodialysisdifficultorevenhazardous),abadheart,orpoorvascularaccesstothebloodsupply.Peritonealdialysisgivesyoumorecontroloverwhen,where,andhowexchangesareperformed.Dependingonyourworksituation,youmaybeabletodialyzeinyourofficewithoutinterruption.Havingaprivatespaceduringexchangescanmakeperitonealdialysisthemoreattractiveoption.Youcanevendialyzeinthecarifyouhavealongdriveaheadofyou.Avoidexchangesinpublicbathroomsorotherplaceswherecontaminationisagreaterpossibility.

Peritonealdialysisalsorequiresfewerdietaryrestrictionsthanhemodialysis.However,thebodylosesalotofproteinduringperitonealdialysis.Youmayneedtotakeaproteinsupplement.Onedrawbackofproteinsupplementsisthatmanyofthemcontainhighlevelsofphosphorus,especiallyiftheycomefromdairyproducts.Oneexcellentoptionispowderedeggwhites,soldbyOptimumNutritionatwww.optimumnutrition.com,whichtastegoodandmixwellwithwater,milk,orjuices.YourlocalGNCstoremaycarrythisproductorcanorderitforyou.Ifyouhavediabetes,youmayhavetroublecontrollingyourbloodsugarwithperitonealdialysis,sincethedialysatecontainsglucose.Talktoyournephrologistaboutthepotentialnutritionalsideeffectsofperitonealdialysis.

Ifyouliketotravelormusttraveloftenforyourjob,peritonealdialysismaybepreferabletohemodialysis.Dialysisbagsandothertreatmenttoolscanbesentdirectlytoyourhotel.(Contactyourequipmentsupplierinadvancetomakearrangementsfordelivery.)Whentravelingbyplane,peoplewhouseCCPDcanplacethecyclerintheoverheadbins,aslongastheyarephysicallycapableof

placethecyclerintheoverheadbins,aslongastheyarephysicallycapableofhandlinga30-poundmachine.Becausecheckedluggagecanbelost,itisagoodideatocarryextracapsandtubinginyourcarry-onluggage.FortravelwithintheUnitedStates,theAmericanswithDisabilitiesActprotectionsshouldallowatravelertotakeadialysismachineonboardtheplane,butwithtoday’sstrictairportsecurityprocedures,youshouldalwayscheckwiththeTransportationServicesAdministrationbeforetravelingwithyourdialysisequipment.Forinternationaltravel,contacttheairlines.

Therearesomedisadvantagesthatmaydampenenthusiasmforperitonealdialysis.Peritonealdialysiscanbetime-consuminganddisruptive(althoughCCPDislessso).Youmustperformdialysiseveryday,regardlessofyouractivities.Generally,youshouldbeabletointegrateexchangesintoyourlife.However,dependingonyourworkortravelschedule,youmayhavetoarrangetododialysisinthecompanyofstrangers,whichyoumayfindembarrassing.Occasionally,youcanskipanexchange,whichisnotadisasteraslongasyourarelydoso.Remember,youwillfeelyourbestifyouperformalloftheexchangesthatyournephrologistprescribes.

Althoughnotascommonasinthepast,infectionslikeperitonitisarestillpossible.Ifyouliveinanareawherethewatersupplycomesfromanunchlorinatedwell,orifyouhaveanyconcernsaboutrecurringinfectionsandshowers,whetherusingcityorwellwater,youshouldconsultyourdoctorforadvice.Also,bediligentaboutcleaningyourexitsiteusingasterilecottonswabdippedinaspecialbleachsolutionyourdialysisnursewillprovide.Theseprecautionsshouldminimizeyourchancesofgettingperitonitis.Ifyoudogetperitonitis,youmightneedtospendoneormoredaysinthehospitalgettingtreatment.Peritonitisistreatable,butifyouhaverecurrentepisodes,youmayneedtohaveyourcatheterremoved.

Peritonealdialysisalsocausesweightgainandanincreasedwaistline,whicharemostlycausedbyfluidretention.Itmaybedifficulttofindclothesthatfitproperly,becauseyourabdomenmaybecomequitelarge.Moreover,youmayfeeluncomfortablewiththedialysatepressingagainstyourabdomen,especiallyifyouhavepolycystickidneydisease(PKD)andlargekidneys.IfyouhavePKD,yournephrologistwillhelpyoutodetermineifperitonealdialysisisagoodchoiceforyou.

Ifyourhomehaslimitedstoragespace,youmayhavetroublestoringyourboxesofdialysateandparaphernalia.Inaddition,carryingheavybagsofsolutionscanbedifficult,especiallyifyouareweakfromthediseaseandhavenoonetohelpyouonadailybasis.Ifyouaresingleandlivealone,peritonealdialysismaynotbeforyou.

dialysismaynotbeforyou.Peritonealdialysisalsorequiresdealingwithaconsiderableamountofwaste.

Theemptyboxes,someofwhichdonotcollapse,cancreateaspecialchallengeifyoudonothavemunicipalcurbsidetrashremoval.Somepeoplemusttransporttheirtrashtoalocaldisposalsite.Ifyouhavetohaulyourowntrash,youwillneedtotransportitmoreoften,especiallyifyoudonothavealargevehicle.Ifyoucannotremoveyourtrashregularly,theamountofdiscardedmaterialcanbecomeoverwhelming.Youmayneedhelpfromyourfamilyorfriendstomanagethetrashproblem.

Peritonealdialysisoffersmanyadvantagesifyouprefertoberesponsibleforandmanageyourowntreatment.Althoughitcanbeverytimeconsuming,peritonealdialysisoffersenoughbenefitsthatitmayworkwellforyou.Talktoyournephrologistandshareyourinterestsandconcerns.Shewillbeabletohelpyoumakeadecisionthatwillbebestforyou.

Hemodialysis

Hemodialysishassomeadvantages.Forexample,itisagoodchoiceforpeoplewholiketospendtimearoundotherpeople.Inaddition,hemodialysistreatmentsprovidestructureandaconsistentscheduletofollow,withtechniciansatacentertakingcareofyou.Allyouhavetodoisshowup,andthenursesandtechniciansdotherest.

Athemodialysiscenters,patientsoftendevelopasenseofcamaraderiewithotherpatientsandthetechnicians.Becauseyouwillbespendingsomuchtimewiththesepeople,ithelpsifeveryoneisongoodterms.Youmayevendevelopsomecloserelationshipsatthedialysiscenterandtheyhelppassthetime.Somepatientsliketalking,whereasothersjustprefertosleepandbeleftalone.Ortheywatchtelevision,read,orworkonalaptop.Insomedialysiscenters,thesocialworkerorganizesactivitiesandexerciseprograms.

Thedisadvantagesofhemodialysisarerelatedtotheadvantages.Althoughpeoplemaypreferhavingaflexibleschedulefortheirdialysistreatments,peoplewithfull-timejobsmaynotbeableeasilytoscheduletreatments.Thestressofcommuting,especiallyinalargemetropolitanarea,justaddstothedifficultyoftravelingtoadialysiscenter.Forthoselivinginruralcommunities,traveldistancestoadialysiscentermaybelong.Gettingtoandfromadialysiscentercanbeaproblemifyoudonotdrive.Publictransportationandtaxicabsareoptions,andmanypeoplehaverelativesandfriendswhoarehappytohelpwithtransportation.Butcare-giversruntheriskofburningoutwhiletheytrytohelpalovedoneandfindtheirownschedulesbecomingoverburdened.Thesocial

workeratthedialysiscentercanassistyouwithfindingsuitabletransportationifyouneedit.

Medically,too,hemodialysishasadisadvantagethatperitonealdialysisdoesnothave.Aswesawpreviously,hemodialysisisanintermittentformofdialysis.Unlikeperitonealdialysis,whichcontinuouslydialyzespatients,hemodialysisallowswasteproductsandimbalancesinbloodchemistriestoaccumulatebetweensessions.Asaresult,youwillhavetomonitoryourfluid,potassium,andphosphorouslevelscarefully.Aswiththeperitonealcatheter,theaccessforhemodialysismaybecomeinfected.

Otherdisadvantagesofhemodialysisinvolvetheprocedureitself.Becauseyourvascularaccess,whetherafistulaorgraft,ispenetratedwithneedles,youmayexperiencediscomfortorpain.Ifyouneedit,askthetechniciantousealocalanesthetic,likelidocaine.

Duringorafterhemodialysis,youmaydevelopcrampsinyourlegsorfeet,oryoumayfeellightheadedwhenyoutrytostandup.Thesesymptomsareduetoexcessfluidremovalduringsessions,whichisneededbecauseyouconsumedtoomuchfluidbetweensessions.Thebestsolutionistorestrictyourfluidintake.Somedialysiscenterswillgiveyouasaltysolutiontodrinkafterasession.Althoughthathelpsatthetime,youmayfeelthirstieranddrinkmorefluidlater.Ifyouhavedifficultiesrestrictingyourfluidintake,talktoyourdieticianaboutstrategiestohelpyou.Youmighttryavoidinghavingdrinksclosebyorsuckingonicechipswhenyouarethirsty.Ifoundnothavingdrinksnearbytobeaparticularlyusefulstrategyinrestrictingfluidintake.Whenworkingandkeepingmymindotherwiseengaged,Isuccessfullykeptmyintaketo1literperday.

Complicationsrelatedtotheaccessmayalsodevelopovertime,includingclotting,infections,andbleeding.Yournephrologistcanmanagemostofthesesideeffects.Ifafistulaorgraftdevelopsablockage,thenaninterventionalradiologistwillbecalledintoremovetheblockage.Shewillinsertacatheterintoamajorveininthegroin,snakeitintothefistulaorgraft,andattempttodislodgetheobstruction.Iftheblockageisabloodclot,theradiologistmayuseanenzymecalledthrombinplasminogenactivator(TPA)todissolveit.Orshemayinsertaballoon,whichcanbeinflatedtoenlargetheinterioroftheaccesssite.Sometimesradiologistscannotrepairthefistulaorgraft,andthepatientwillneedanewaccess.

DIET

Fluidanddietaryrestrictionsaremoredifficulttomanagewithhemodialysisthantheyarewithperitonealdialysis.Thisisespeciallytrueforcontrolling

thantheyarewithperitonealdialysis.Thisisespeciallytrueforcontrollingsodium,potassium,andphosphorus.

Excesssalt(sodium)retention(andthereforefluidretention)isoftenthemostdifficulttomanage.Saltisinalmosteverythingweeat,andsodiumlevelsareespeciallyhighinprocessedfoodsandrestaurantfoods.Thus,knowinghowmuchsodiumyouareconsumingbecomescritical.Hereiswhathappensifyouingesttoomuchsalt.

Thebodyusessalt(sodiumchloride)tokeepabalancebetweenthevolumeofbloodandthevolumeoffluidinthetissues.Theproperbalanceisessentialforhealthyhydration.Ingestingtoomuchsalthasseveralconsequences.Thesodiumdrawswaterfromcellsinthebloodstreamandintothetissuesoutsideofcells.Thiscanraisethevolumeofbloodandcancontributetohypertension.Theoverfilledtissuesswell,causingfluidretentioninthelegsandfeet.Inaddition,excessfluidinandaroundthelungscancauseshortnessofbreath.Excesssaltingestionalsostimulatesthirst,whichcanleadapersontodrinktoomuchfluid,causingfluidoverloadinthebody.Youcanminimizefluidretentionbystrictlycontrollingbothyoursaltintakeandyourfluidintake.Forsomepeoplethenephrologistwillestablishalimitof1liter(approximately1quart)offluidsaday.

Potassiumlevelsinthebloodmustbepreventedfromrisingtoohigh.Thebestwaytocontrolpotassiumlevelsisbyrestrictingpotassiuminyourdiet.Highpotassiumconcentrationsinthebloodcanleadtoheartspasmsandpotentiallydeath.Therefore,limithigh-potassiumfoods,likeorangejuice,bananas,tomatopaste,potatoes,andcolas.Seetable6.1foracompletelistoffoodstoavoid.Table6.2listsfoodswithlowamountsofpotassium.

Highphosphoruslevelshavelong-termimplications—unlikehighsodiumandpotassiumlevels,whichposemoreimmediateconcerns.Aswelearnedinchapter4,highphosphoruscanleadtoweakenedbonesandtotheformationofplaquesinvariousorgans.Avoidfoodsthatarehighinphosphorus(seetable6.3).Takephosphatebindersifyournephrologistprescribesthem.Table6.4suggestshowtosubstitutefoodwithlowphosphoruslevelsforfoodswithhighlevels.

Readfoodlabelstoidentifypotentiallyharmfulingredients.Considergettinganutritionalguidetosomeofthefoodsyoucommonlyeat.TheAmericanAssociationofKidneyPatientsoffersafreeguideontheirwebsite,whichincludessodium,potassium,phosphorus,protein,andcaloricvalues(seewww.aakp.org).

Youmayfeeloverwhelmedatfirstbythelistofdietarydosanddon’ts.A

Youmayfeeloverwhelmedatfirstbythelistofdietarydosanddon’ts.Adietitiancanhelpyouavoidthewrongfoods,whileshowingyouhowtocontinueeatingsomeofthefoodsyoulove.Restrictingyourdietmaybedifficultatfirst,butwhenyoubegintofeelsomuchbetter,youwilldecideitisworthit.Overtime,trackingfoodvaluesbecomessecondnature.

Table6.1FoodswithHighLevelsofPotassium

Thehealthieryourdietis,thefewercomplicationsyouarelikelytohave.Eatingrightrequiresself-disciplineandunderstandingfromyourfamilyandfriends,whomustbesensitivetoyourdietaryneeds,sinceyoumaynotbeabletoeatwhattheyserve.Attimes,youmayhavecravingsforfoodsthatyoushouldnoteat.Youmayfindthatyoucanoccasionallyeatthesefoods,butdososparinglyandinsmallquantities.Youmayfindthatyouneedonlythetasteof

thesefoodstofeelsatisfied.Sticktoyourbasicdiet(seechapter5)andavoidforbiddenfoodsandyouwillprobablybeokay.Behonestwithyourdietitianandnephrologistaboutwhatyouareeating,especiallyifyourbloodchemistriesareabnormal.Theywillbeabletohelpyoumodifyyourdiettokeepyouhealthyandallowyoutoeatsomeofthefoodsyoulike.

Table6.2FoodswithLowLevelsofPotassium

Table6.3FoodswithHighLevelsofPhosphorus

RESTLESSLEGSSYNDROME

Peopleundergoinghemodialysismayexperiencerestlesslegssyndrome.Estimatesofthepercentageofpeopleaffectedrangefrom6to60percentofpeoplehavinghemodialysis.Restlesslegssyndrome,aneurologicaldiseasewithanunknowncause,isastrongurgetomovethelegsthatisdifficulttoresist.Patientsdescriberestlesslegssyndromeascreepy-crawly,itching,pulling,tugging,orgnawingsensations.Thesesensationsbeginwhenthepersonisatrest,notmoving,andespeciallywhengoingtosleep.Thesymptomsofrestlesslegssyndromecanbeextremelyunpleasant.Youmayhaveanuncontrollableurgetomoveandjerkyourlegs.Ifyouresistit,thenegativefeelingsmaybeoverwhelming,almostpainful.Movingmaybetheonlywayforthesensationstostop.Ultimately,youmaygetlittlesleepandfeelexhaustedduringtheday.

Table6.4Low-PhosphorusSubstitutionsforHigh-PhosphorusFoods

Treatmentsareavailabletorelievethesymptomsofrestlesslegssyndrome.Todeterminewhetherthesetreatmentsarerightforyou,yournephrologistwillfirstexamineyournutritionalstatus.Deficienciesinironandcertainvitamins,likeB-12andfolate,cancontributetorestlesslegssyndrome.However,sincemostpeopleondialysistakeironandvitaminsupplements,nutritionisusuallynotthecauseofrestlesslegssyndromeforthem.

Variousmedicationscanhelprelievethesymptomsofrestlesslegssyndrome.Forpeoplewithchronickidneyfailure,lowdosesofadruglikeclonazepam(Klonopin),whichisabenzodiazepinederivativewithanticonvulsant,musclerelaxant,andanxiety-relievingproperties,mayproviderelief.Otherdrugsinthissameclassmaygiveyouahangover,however.Clonazepamworksverywell,evenusingthelowestdoseneededtoalleviatethesymptoms.Ifyouhaverestlesslegssyndrome,treatmentwithclonazepammayhelpyougetagoodnight’ssleepandfeelrestedduringtheday.

Anticonvulsantsareanotherclassofdrugsyournephrologistmayprescribe.OriginallydevelopedtotreatParkinson’sdisease,anticonvulsantslike

OriginallydevelopedtotreatParkinson’sdisease,anticonvulsantslikepramipexole(Mirapex)andropinirole(Requip)maybehelpfulintreatingrestlesslegssyndrome.Thedownsideisthatanticonvulsantdrugshavecausednausea,lightheadedness,and,inrarecases,hallucinationsinsomepeopletakingthesemedicationstotreatParkinson’sdisease.SincetreatingrestlesslegssyndromerequireslowerdosesofthesedrugsthanforParkinson’sdisease,thesideeffectsmaynotbeassevere.

Ifyouhaverestlesslegssyndrome,talktoyournephrologist.Youdonothavetosufferfromthisdisorder.

Noonelikesdialysis,anditisneitherriskfreenorcomplicationfree.However,itispossibletomakedialysistolerableandtolimithowmuchitinterfereswithyouractivities.Talkaboutyouroptionswithyournephrologist,andunderstandyourowntemperamentandlifestyle.Ifyoucannotobtainatransplantfromalivingdonorbeforegoingondialysis,thewaitingtimeforkidneytransplantscanbelong.Helpyourselfduringthistimebycomplyingwithyourtreatment,followingyourprescribeddiet,restrictingyourfluidintake,andtakingyourmedications.Takingcareofyourselfwillmakedialysistolerableandwillkeepyouinthebesthealthpossible.

Asuccessfulkidneytransplantmaybeyourbestchanceatlivingalongandhealthylife.That’sthetopicofthefollowingchapter.

7TRANSPLANTATION

Weliveinaconsumersociety.Webuythingsandwethrowthingsaway,sometimeswithlittlethought.Butmanypeoplearedevelopingagreaterawarenessthatdiscardeditemspileupinlandfills,andasaresulttheyaretakingstepstorecycleandreusematerialswhentheycan.

Manypeoplenowvieworgantransplantationthesameway.Peoplewhomightotherwisediebecauseoforganfailurecanlivelongerlivesthroughtransplantationoforgansfromlivingordeceaseddonors.Surgeonscantransplantkidneys,livers,hearts,lungs,pancreases,intestines,bowels,bone,tendons,veins,corneas,andskin.

Organtransplantationhascomealongwayoverthelastthirtyyears.Intheearlyyearsoftransplantation,doctorsthoughttheycouldonlytransplantaviableorganfromonepersontoanotherifthedonorandtherecipientwereidenticaltwins—otherwise,therecipient’sbodywouldrejectthedonatedorgan.Modernmedicinehasmademajoradvancesinthetechniquesoftransplantation,andnewdrugshavebeendevelopedthatsuppressthebody’snormalreactionofrejectingaforeignbody.Howdoestransplantationwork?Howisitevenpossible?Thischapterexploresthesequestionsandexplainsthetransplantationprocess.

Whenmedicalsciencegainedanunderstandingofhowtheimmunesystemfightsoffforeigninvaders,itwasabletodeveloptreatmentstopreventorganrejection.Forexample,scientistsusedthisknowledgetocreatevaccinestohelpthebodydestroyspecificinvadingorganismslikethosethatcausepolio.Thevaccineshelpedthebodyproduceproteins,calledantibodies,whichattacktheinvadingorganismsandcausetheirdeath.Butevenwithoutavaccination,thehealthyimmunesystemdispatchesanarmyofcellstokillmanybacteria,viruses,andothermicroorganismsitencountersthatdonotbelonginourbodies.Thehealthyimmunesystemisprettyamazing.Buthere’sthedownsideforpeoplewhoneedtransplants:becausethebodyconsiderstransplantedorganstobeforeign,theimmunesystemwillattackthem.

Thebodyhasaningeniouswayofknowingwhatbelongstoitandwhatdoesnot:everycellinaperson’sbodypossessesamarker—a“nametag”ofsorts—thatdistinguishesitfromthecellsinanotherperson’sbody.Whencellswithdifferentnametagsbumpintoeachother,aseriesofreactionsoccur,sometimesleadingtothedestructionofthecellsthatdonotbelong.

leadingtothedestructionofthecellsthatdonotbelong.Thesenametagsareknownasantigens.Insidethebody,cellscalled

lymphocytesrecognizewhethertheantigenbelongstoyouortosomeoneorsomethingelse.Ifyourlymphocytesencounterrecognizablecells,nothinghappens.However,ifyourlymphocytesdonotrecognizeacell’santigens,theinvadingcellsarekilled.Inthecaseoforgantransplants,aspecializedlymphocytecalledaT-lymphocytedestroystheorgan.Whenwearetalkingabouttransplantation,werefertothedegreetowhichthecellsarecompatiblewithoneanother,andthereforethenametagsrelevanttotransplantsarecalledhistocompatibilityantigens,orhumanleukocyteantigens(HLA).

YourHLAtypingandtheHLAtypingofthedonordefinehowcompatibleadonorkidneymaybe.Onlysixofthemanyhistocompatibilityantigensmustbeknownbeforeyourcompatibilityforakidneytransplantfromanotherpersoncanbeevaluated.Thesesixantigenscomeinmorethanonehundredformsandarenotequallypresentinthepopulation.Somearemorecommonthanothers.ThemostcommonHLAantigensarepresentinabout20percentofthepopulation,whereasothersarepresentinlessthan1percentofthepopulation.Inaddition,someHLAantigensprovideastrongerimmuneresponsethanothersdo.Thesevariablesmeanthatfindingasimilarmatchfromsomeoneoutsideyourfamilycanbedifficult.

Untilrecently,foratransplanttosucceed,theseantigenshadtobecloselymatched.Now,becauseresearchershavedevelopedmoreeffectiveanti-rejectiondrugs,anantigenmatchislessimportantthanitoncewas.Aperfectmatchisstillbest,butlessthanperfectmatchescanbemanagedalmostequallywellwiththelatestimmunosuppressantmedications.

AreYouaCandidate?Kidneytransplantationisthetreatmentofchoiceforkidneyfailure,allowingforthebestqualityoflife.Yournephrologistwilldeterminewhetheryouareeligibletoreceiveone.Akidneytransplantisaseriousoperation,andlivingwithatransplantedkidneyrequireslifelongcare.Anydonatedorganisavaluablegiftthatmustbegivenonlytopeoplewhowilltakecareofit.Therefore,youmusttakeallprescribedmedications,keepyourdoctors’appointments,andtakecareofyourself.

Yournephrologistwillassesswhetheryouwillbearesponsibletransplantrecipientbasedonyourpreviousbehavior.Forexample,ifyouareondialysis,yournephrologistwillfindoutwhetheryoucametothedialysiscenterforallof

yourtreatments(orperformedallofyourprescribedexchanges,ifyouareonperitonealdialysis).Inaddition,hewillcheckthatyouhavetakenallyourmedicationsandcompliedwithanyprescribeddietaryrestrictions.Withanewkidney,yourqualityoflifewillimprove,butthatdoesnotmeanthatyourhealthisnolongeranissue.Afterall,atransplantisnotacureforkidneyfailure;itisonlyatreatment.Thus,ifyournephrologistdoesnotthinkthatyouwillbecompliant,hewillnotrecommendyouforatransplant.

Severalotherconditionscanmakeitdifficulttoreceiveatransplant.Becausetheimmunesystemwillbedeliberatelysuppressedwithmedicationsafteratransplant,youcannothaveanactiveinfectionoruncontrolledinfectiousdisease,likeabacterialinfection,atthetimeofthetransplant.IfyouareHIVpositiveorhavehepatitisBorC,youcanreceiveatransplant,butcomplicationsaremorelikely.Tobeeligibleforatransplant,youmustnothavecancerorsmoke.Evidenceofdrugoralcoholabusewillpreventyoufromgettingatransplantuntiltheproblemhasbeenresolved.Obesitymayalsoexcludeyoufromreceivingatransplant.Althoughthepoliciesoftransplantcentersvary,yourpotentiallongevitywillbeassessedtodeterminewhetheryouwouldbenefitfromatransplant,especiallyifyoudonothavealivingdonor.Thewaitingtimeforadeceaseddonormaybeyears,soyourlikelyfutureconditionwillbetakenintoconsideration.

Onahappiernote,manypeopledoqualifyastransplantrecipients.Theprospectofreceivingatransplantcanbeveryexciting,especiallyifyouhavebeenondialysisforalongtime.Yourabilitytowork,toengageinactivitiesyoulove,andtojustfeelnormalagainwillimprovewithasuccessfultransplant.Thischaptercoversthestepsyouwilltakeiftransplantationisanoptionforyou.

Figure7.1.NumberofTransplantCandidatesonWaitingList,1987–2010

DonorsThenumberofpeoplereceivingkidneytransplantshasbeensteadilyincreasingsince1987.Eversincekidneytransplantationbegan,therehavebeenfewerkidneydonorsavailablethanthenumberofkidneydonorsthatareneeded(aswesawinchapter1).AsofOctober2010,accordingtotheUnitedNetworkofOrganSharing(UNOS),over86,000candidatesintheUnitedStateswerewaitingforkidneytransplants,continuingthistrend(seefigure7.1).In2009,16,829peoplereceivedkidneytransplants,downfromahighof17,095in2006(seefigure7.2).

Kidneyscomefromtwotypesofdonors:livingdonorsanddeceaseddonors.Aswelearnedabove,notenoughkidneysareavailableandacceptablefortransplantation.Thismeanslongwaittimesformanypatients.ThisisespeciallytrueforpeoplewithtypeOblood,themostcommonbloodtype,becausesomanytypeOpotentialrecipientsexistfordonationsfromtypeOdonors.Survivalratesforkidneyrecipientsfrombothlivinganddeceaseddonorsarequitegood.Table7.1displaystheone-year,three-year,andfive-yearkidneysurvivalratesaswellaspatientsurvivalratesforpeoplewhoreceivedakidneyfromlivingdonorsversusthosefromdeceaseddonors.(Kidneysurvivalmeanslivingwithoutdialysisoranothertransplant.)Patientsurvivalisbetterthan

kidneysurvival,becausepatientsmaygobackondialysisafterlosingakidneywhiletheywaitforanothertransplant.

Figure7.2.NumberofTransplantsbyDonorType,1988–2009

Anotherwaytomeasuresurvivalisusingthehalf-life.Thehalf-lifeisthetimethatrepresents50percentofthosesurvivingkidneysthatreachthatpoint.Thehalf-lifeofakidneyfromalivingdonoris20to25years,whilethehalf-lifeofakidneyfromadeceaseddonoris7to10years.Thus,halfofpeoplereceivingakidneyfromalivingdonorwillstillhavethatkidneyfunctioningfor20to25years,andhalfofpeoplereceivingakidneyfromadeceaseddonorwillstillhavethatkidneyfunctioningin7to10years.

Table7.1KidneyTransplantSurvivalRates

LivingDonors

Thepublicismoreawareoftheneedfororgandonationsthaneverbeforeand,asaresult,morepeoplearepromisingtodonatetheirorganswhentheydie.However,manyorgansareneedednowtosavethelivesofpeoplewhoseorganshavefailed.Newinterestinlivingdonationhasgivenhopetomanypatientsinneedofakidneytransplant.Since1988,accordingtoUNOS,thetotalnumberoflivingdonationssteadilyincreased,peakingin2004.Thenumberoflivingdonationshasbeensteadysincethen(seefigure7.2).Asapercentageofkidneytransplants,livingdonationsalsoincreased,untilpeakingatalmost43percentin2003andthendecliningto38percentin2009(seefigure7.3).Thedeclineinlivingdonationsasapercentageofallkidneytransplantsisaresultoftherapidswellinginthenumberofpeopleneedingtransplants,aswellasofanincreasedavailabilityofmoreusableorgansfromdeceaseddonors.

Figure7.3.PercentageofTransplantsbyDonorType,1988–2009

Kidneysreceivedfromlivingdonorsgenerallyhavebettersuccessratesthanthosereceivedfromdeceaseddonors.Youmaywanttofindapersonwillingtodonateakidneytoyou—althoughapproachingsomeoneaboutalivingorgandonationmaybeawkward.Afterall,youareaskingsomeonetogiveupabodypart,riskingherownhealthandwithnomedicalbenefittoher.Therefore,thegifthastobetrulyaltruistic.Oneapproachtofindingadonorismakingyourcircumstancesknowntoyourfamily,friends,orgroupsyouareinvolvedin.Ifsomeoneisinterestedindonatingakidneytoyou,heorshewillapproachyou.

someoneisinterestedindonatingakidneytoyou,heorshewillapproachyou.Anothersourceofdonationsisakidneypool.Inrecentyearstherehasbeen

anincreaseinthenumberofindividualsdonatingkidneystoanon-directedpoolofrecipientsthroughorganizationsliketheNewEnglandProgramforKidneyExchange(NEPKE),MatchingDonors.com,andtheNationalKidneyRegistry(seetheResourcessectionattheendofthebook).Indonorpoolslikethese,anonymousor“GoodSamaritan”donorsdonotspecifythepersonreceivingthetransplant.Toensurethattheirgiftissuitable,donorsmustbethoroughlyscreenedandeducatedaboutthepotentialrisks.Moreover,theymustnotbecompensatedfortheirdonation,sincecashpaymentsfororgandonationsareillegalintheUnitedStates.Ifdonationstoanon-directedpoolbecomemorecommon,theycouldhelprelievetheimbalancebetweenthenumberoforgansavailableandthenumberoforgansneeded.

Ifyouaretemptedtobuyakidneyabroad,donotdoit!Studieshaveshownthatpeoplewhodosogenerallyhavepooreroutcomes.Becausethedonorsaremotivatedbymoney,theymaynotbewellscreenedmedically.Medicaltourismhasbecomeaflourishingbusiness;marketingpracticesnowincludethetemptationofexoticvacationscoupledwithatransplantfromalivingdonor.Don’tbefooled:itisnotworththerisk.Ifyouhaveafamilymemberorfriendlivingabroad,however,thatopportunitymaybeworthpursuingaslongasthedonoristhoroughlyscreenedandaslongasitisagoodmatch.Explorethispossibilityonlythroughreputabletransplantcentersabroad.Talktoyourlocaltransplantcenterforadvice.

Althoughmanydirectkidneydonationsfromlovedoneshavegoodoutcomes,apotentialdonormaynotbecompatible,usuallybecauseofanunacceptablebloodtypeorapreexistingdiseaselikepolycystickidneydisease(PKD).Inanattempttoincreaselivingdonation,bettermethodshavebeendevisedtoscreenandmatchdonorsandrecipients,sothatmoretransplantsmightbepossible(seetheResourcessectionfordetails).

Ifyoufindawillingdonorbutthatpersonisnotasuitablematch,youmaybeabletotakeadvantageofasystemofswapping,commonlycalledapairedkidneydonation.Hereishowitworks.Ifyouhaveanincompatibledonor,yourtransplantcenterwilltrytolocateanothertransplantcandidatewhoseincompatibledonoriscompatiblewithyou.Ifyourdonoriscompatiblewiththeothercandidate,youcanswapdonors.Iftheseconddonorisnotcompatiblewithyou,yourtransplantcentermaytrytofindothercandidate-donorpairswhereonedonoriscompatiblewithyou,andtheirincompatibledonorsarecompatible

withtheothercandidates.Insuchacase,amorecomplexcandidate-donorswapcanbeperformed.AGoodSamaritandonorcaneveninitiateachainofdonationsifheorsheiscompatiblewithacandidatewhodoesnothaveothercompatibledonorsavailable.

Withtoday’sadvancesinremovalandtransferofakidneyfromalivingperson,mostsurgeonscanremoveadonor’skidneylaparoscopically.Inlaparoscopicremoval,thesurgeonmakessmallincisionsintheabdomenandthenextractsthekidneythroughoneoftheincisions.Theotherincisionsallowthesurgeontoinsertavideocameraandsurgicalinstruments.Aminimallyinvasivelaparoscopicoperationmeansquickerrecuperationforthedonorthanintraditionalremovalmethods,whichrequireanincisionundertheribcageandwhichcancausegreaterdiscomfortandlongerrecoverytimes.

Whenyouarereadyforatransplant,thetransplantteamwillorganizeameetingwithyourdonor,whomyoumayormaynothavealreadymet,toexplaintheprocessandtoansweranyquestionsaboutlivingdonation,thesurgicalprocedure,andtheshort-termandlong-termrisksassociatedwithadonation.Thesemeetingsmayincludefamilyandfriends.Allinformationgatheredaboutthepatientsandtheprocedureisconfidential.Yourtransplantteammayseparateyouandyourdonorforcounselingandexamination.Yourdonorwillbeseenbyanephrologistdifferentfromyoursfortheworkup.Yourdonorandyouwillalsohavedifferentsurgeons.Medicarenowrequiresthateveryprogramhavealivingdonoradvocatewhoisavailabletotalktoyourdonoraboutconcernsorreservations.Medicareandmostmedicalinsuranceplanscoverthecostoftestingthedonorforcompatibility.

Bothyouandyourdonorwillundergoextensivephysicalexaminations,beaskedtoprovideyourmedicalhistories,andwillundergoabatteryoftestsperformedbyyourrespectivemedicalteamstoensurethatyourkidneysarecompatibleandthatdonatingakidneywillnotadverselyaffectthedonor’shealth.Inaddition,yourdonor’snephrologistwillmakesurethedonordoesnothavekidneydiseaseandthatheorshehastwokidneys;thedonor’snephrologistwillruleoutanyinfectiousdiseaseorcancerriskthatthedonatedkidneymayposetoyou.Iftherearewarningsignsofpotentialpitfallsatanypointintheprocess,yourdonorcanoptout.

Theteamwilldiscusswithyou,therecipientofatransplant,what’sinvolvedinyoursurgery,whatwilltakeplaceduringthehospitalization,andwhatyouwillneedbywayoffollow-upcareafteryouaredischargedfromthehospital.Acrucialpartofyouraftercareisthemedicationsyouwillneedtotaketohelpyourbodyresistrejectingyournewkidneyandbecominginfectedbyvarious

yourbodyresistrejectingyournewkidneyandbecominginfectedbyvariousmicroorganisms.Therefore,thetransplantteamwilldiscussyourabilitytopayforyourmedications,whichcanbeveryexpensive,tomakesurethatyouhaveadequateinsuranceorotherfinancialmeanstocovertheircosts.Medicarewillcovermostofthecostsofmedicationsforthreeyearsaftersurgery,butfornow(legislationispendinginCongresstoremovethethree-yearlimit)otherhealthinsurancepoliciesorpersonalfundswillbeneededtocovertherestofthecostforthefirstthreeyearsandmostofthecostafterthat.

Inmostcasesyouandyourdonormusthavecompatiblebloodtypes,althoughsomecentershavetransplantedblood-incompatiblecandidatesonanexperimentalbasis.Becauseofthewayweinheritbloodtypes,somebloodtypesarecompatibleandsomearenot(seetable7.2).Forexample,ifyouhavetypeOandyourdonorhastypeA,B,orAB,yourimmunesystemwillrejectyourdonor’skidney.Thus,youbothmusthavetypeOblood.Ontheotherhand,ifyouhavetypeA,B,orAB,youcanacceptakidneyfromyourdonornotonlyifheorshehasthesamebloodtype,butalsoifhehastypeO.TypeOisknownastheuniversaldonor.IfyouhavetypeAB,youcanacceptyourdonor’skidneyregardlessofhisbloodtype,makingtypeABauniversalacceptor.

Table7.2BloodTypeCompatibility

Otherbloodtestswillassessyourandyourdonor’sgeneralhealth,andcanrevealwhethereitherofyouhasanyactiveinfections,includinghepatitisorHIV/AIDS.Anelectrocardiogram(EKG)andstresstestwillbedonetoassesstheactivityandfunctionoftheheart,toruleoutunderlyingcardiacconditionsthatmightendangerthehealthofyouoryourdonorduringoraftersurgery.Anyconditionthatcouldharmyourdonor’sremainingkidney,likehighbloodpressureordiabetes,woulddisqualifyhimasacandidate.Finally,asocialworkerwillconductaninterviewwithyourdonortoassesswhetherthekidneyisbeingdonatedfortherightreasonsandnotinexchangeforpaymentorsomeothercompensation.

DeceasedDonors

Organsmayalsobeobtainedfromarecentlydeceasedperson(cadaver).Not

surprisingly,organsfromdeceaseddonorsaremoredifficulttomatchtorecipientsthanlivingdonationsare.Withmorepeopleneedingkidneytransplantsthantherearekidneysavailable,theU.S.government,throughacontractwithUNOS,hasestablishedwhatitbelievesisafairandequitableproceduretoallocateandmatchkidneys.

Accordingtoitswebsite(www.unos.org),UNOScoordinatesorgantransplantationsofalltypeswiththetransplantcentersthroughouttheUnitedStates.UNOSalsocoordinatesmultiple-organtransplants,likekidney/pancreasandheart/lung.AsofOctober2010,UNOSmaintainedadatabaseforallorgansofmorethan108,930peopleneedinganorgan.UNOSoversaw28,464transplantsin2009.

TheUNOSdatabasehelpsmatchorgansfromdeceaseddonorstoappropriatecandidates.Whenkidneysbecomeavailable,theorganprocurementteamremovesthemandsendsinformationaboutthebloodandtissuetypesviacomputertoUNOS,wherestaffmembersmatchpotentialcandidatesonthewaitinglist.Usingthebloodtype,sizeoftheorgan,thepatient’stimeonthewaitinglistandmedicalurgency,aswellasthegeographicdistancebetweenthedonorandpatient,thecomputergeneratesalistofpotentialcandidates.

Thetransplantcoordinatorinthetransplantcenterthencontactsthetransplantsurgeonscaringforthesepatients.Eachkidneyhasoneprimaryrecipientandatleastonebackuprecipient.Becausetimeiscrucial,thetransplantcenterisrequiredtospendonlyonehourtryingtocontacttheprimaryandbackupcandidatesbeforeUNOSgoestotheothercandidatesonthewaitinglist.Tominimizethetimebetweenrecoveringakidneyfromadonorandplacingitinacandidate,UNOSdividestheUnitedStatesintoelevenregions(seefigure7.4).

Whenacandidateonthewaitinglistmatchesperfectlywithanavailabledonorkidney,thatcandidategoestothetopofthenationallistregardlessofhowlongheorshehasbeenonthelist.About20percentoftransplantsfromdeceaseddonorsareaperfectmatch.Whennocandidatematchesperfectlywiththeavailabledonorkidney,UNOSoffersthekidneyfirsttoacandidatewiththenextbestmatchlivinginthesamelocality,andthenlivinginthesameregion,beforeofferingittotherestofthecountry.Additionalconsiderationisgiventhoseunder25yearsoldandhighlysensitizedindividuals(thosewhohavehadprevioustransplants,transfusions,orpregnancies,inthecaseofwomen)becausetheseconditionsintroduceforeigncellsintothecandidate,increasingthechancesofrejection.Furthermore,somekidneysaretransplantedalongwithaheartoralivertothecandidatewhenthepersonhaskidneyfailureaswellassevereheartorliverfailure.

severeheartorliverfailure.

Figure7.4.TheElevenNationalRegionsoftheUnitedNetworkofOrganSharing

Althoughacandidate’schancesofreceivingatransplantimprovethelongerheisonthelist,candidatesdonotactuallyoccupyaparticularslot.Rankingoccursonlywhenakidneybecomesavailable.Untilrecently,theprimaryconsiderationforatransplantdependedontheextenttowhichtheHLAtypeofthecandidatematchedtheHLAtypeofadonorwiththesamebloodtype.Now,aperfectmatchstillgoestothetopofthelist,whereaswithkidneysforwhichthereisnoperfectmatchonthewaitinglist,thetimeacandidatehasspentonthewaitinglistisapredominantcriterion.

Unlikecandidatesreceivingtransplantsfromlivingdonors,wherethereareoptionsforbloodtypecompatibility,anorganfromadeceaseddonormustbeanexactmatch.Requiringanexactmatchprovidesfairnessforpeoplewithaparticularbloodtype.GivingkidneysfromdonorswithtypeObloodtopeoplewithotherbloodtypes,whilepossible,wouldcreateagreatershortagethanexistsnowfortypeOcandidates,meaninganevenlongerwaittime,whichiscurrentlythelongestforallcandidates.Therefore,itisnotdone.Onceanexactbloodtypematchisestablished,thecellsfromthedeceaseddonorandfromthecandidateundergofurthertesting.

Therearetwoclassesofkidneysfromdeceaseddonors:standardcriteriadonorsandexpandedcriteriadonors.Expandedcriteriadonorsdifferfromstandardcriteriadonorsbyageandmedicalcondition.Anydonorsover60yearsoldareconsideredexpandedcriteriadonors.Expandedcriteriadonorsalsoincludepeopleover50yearsofagewithanytwoofthefollowing

includepeopleover50yearsofagewithanytwoofthefollowingcharacteristics:highbloodpressure,heartattackorstroke,diabetes,orabloodcreatinineover1.5mg/dl.Anexpandedcriteriadonormaybeanoptionforpeoplewithcomplicationsthatmaymakeitimpossibleforthemtowaitverylongforatransplant.However,kidneysfromexpandedcriteriadonorstypicallydonotfunctionwellinthebeginningandmayhaveashortersurvival.

Thebestcandidatesforanexpandedcriteriadonationarepeoplewithdiabetesovertheageof40andpeopleover50whosebloodsupplyisdifficulttoaccessfordialysis.Candidatesonthewaitinglistmayreceivetransplantsfromanexpandedcriteriadonorsoonerthanreceivingonefromastandardcriteriadonor.Ifanexpandedcriteriadonorinterestsyou,talktoyournephrologistandtransplantteamtofindoutwhetheritisanoptionforyouunderyourmedicalcircumstances.

Elderlypeoplemaywanttoconsideranexpandedcriteriadonor,althoughtheirgeneraleligibilityforatransplantwilldependlargelyontheiroverallhealthstatus.Anephrologistwillassessthebenefitsandrisksofatransplanttoassesswhethertransplantationwouldincreasetheirlifespanandqualityoflife,comparedwithstayingondialysis.Becausekidneysfromexpandedcriteriadonorsmaynotinitiallyfunctionnormally,recipientsmustbehealthyenoughtotoleratebothdialysisandtheeffectsofimmunosuppression.Theirnephrologistwillhelpthemdecideifatransplantisappropriateforthematthatstageoflife.

Beforeanytransplant,laboratorytestswillbedonetoassessthelikelihoodthatthecandidate’simmunesystemwillrejectthetransplantedorgan.OnetestcomparesthePanelReactiveAntibody(PRA)ofthedonorandthecandidate.PRAmeasurestheamountofantibodiesinthebloodasawayofassessingtheprobabilityofrejection.WithahighPRA,chancesofrejectionincrease.Theseantibodies,whichcansensitizeakidneytorejection,canbepresentasaresultofprevioustransplants,bloodtransfusions,adiseaselikelupus,orpregnancies.

Theothertestisthecytotoxiccrossmatch,wherelymphocytesfromthedeceaseddonoraremixedwiththecandidate’sbloodtodeterminewhetherantibodiesareproducedinthecandidate’sbloodthatcouldcauseimmediaterejectionofthekidney.Apositivecrossmatchindicatescertainrejection.Thus,anegativecrossmatchisdesired.Oncethesecriteriahavebeensatisfied,thetransplantsurgerycanproceed.

UNOSiscurrentlydevelopinganewsystemforallocationthatwillmakebetteruseoftransplantedorgans,matchingkidneyswithpeoplewhohavethegreatestexpectedsurvivaltime.Asofthiswriting,thesystemhasnotgoneintoeffect.ChecktheUNOSwebsite,www.unos.org,orconsultyourtransplantteam

forupdates.

WaitingforaTransplant

Thewaitforakidneytransplantcanbefrustratingandcanseemendless.1Manypeoplewithkidneyfailuredecidetogetakidneytransplantratherthanstartorcontinuedialysis.Afterundergoingalltheextensivetestsandfinallybeingplacedonthetransplantlist,thewaitbegins.Foraluckyfew,thewaitisshort.Somepeoplereceivetransplantswithinmonths.However,mostpeoplewaitforyearsforatransplant.Forpeoplewhohavenotfoundacompatiblekidneyfromalivingdonor,thewaitisaboutthreetosevenyears.Waittimesalsovarydependingonwhereinthecountryacandidatelives.Iwasonthelistformorethansevenyears,andthewaitwasoftendifficult.

WhenIfirststarteddialysis,Iwasquiteill.Ididn’tthinkmuchabouttransplantationuntilIbecamewellenoughtoconsiderit.Thenmybiggestconcernwasbeingunavailabletomytransplantcoordinatorwhocouldcallatanytimetosay,“It’stime.”Likemanypeopleonthewaitlist,Icarriedacellphone;Ialsohadapagerwithmeatalltimes,notknowingwhetherIwouldreceiveasignalwheninalargebuildingorfarawayfromhome.

ThelongerIwasonthetransplantlist,thelessIwantedtotravelveryfarfromhome.WhereverIwent,ImadesurethetransplantcoordinatorknewwhereIwasandhowshecouldcontactme.Evenso,Iwasalwaysconcernedaboutreceivingacallorreturningintimetoreceivemykidney.Althoughasurgeoncaneffectivelytransplantakidneywithintwenty-fourhours,thechancesthatthekidneywillfunctionimmediatelydecreasewithincreasingtimeafterremovalfromthedonor.Consequently,IlivedinfearthatIwouldmissthatgreatgiftoflifebybeinginthewrongplaceattherighttime.

Thoseofusonthetransplantlistknowthatwehavelimitedabilitytoplanforthedaythetransplantcoordinatorcalls.Wecouldhaveabagpackedandhavefamilyandfriendsreadytohelp,butwedonotknowforsureifourplanswillwork.Itisnotasifweknowexactlywhenourtransplantwillhappen.OverthesevenandahalfyearsIlivedwithdialysis,althoughIoftenfoundmyselfbecomingincreasinglyanxiousaboutmyavailabilityforatransplant,allIcoulddowasstayincontactwiththehospital,hanginthere,livemylifethebestwayIcould,andwait.Althoughpatiencemaybeavirtue,attimesIfoundithardtomaintain.Atsomepoint,weneedfaiththatintheend,everythingwillworkout.Wewillreceiveourtransplant,andourliveswillimprove.

HavingaTransplant

Whenthetimecomesforyourtransplant,itisoftenasurprise.Manycandidateswaitingfortransplantsreceivenumerouscallsthatdonotpanout.BecauseUNOSdoesnotknowforsurewhethertheprimarycandidatesareavailable,manycandidatesreceivecallsaspossiblebackupstodeterminetheirreadiness.Eventually,youwillpercolatetothetopofthelistandfinallygetyourcallasaprimarycandidate.

Onceyoureceivethecallandaccepttheorgan,youwillgotothetransplantcentertoprepareforsurgery.Thecenterwillperformbloodteststomakesureyourhealthisgoodenoughforthetransplantsurgerytoproceed.Partofwaitingforsurgeryinvolvesthetimetotransportthekidneytothecenterandtocompletethecrossmatchtoensurethatyouwillnotrejectyournewkidneyimmediately.Asoneofthefinalpreparationsforsurgery,anursewillinsertacatheterintoavein,andtheanesthesiologistwillbeginadministeringsedatives.Onceintheoperatingroom,theanesthesiologistwillgiveyougeneralanesthesia.

Thetransplantitself,whetherthekidneycomesfromalivingordeceaseddonor,isrelativelysimple,asfigure7.5illustrates.Inlivingdonations,leftkidneysaretransplantedbecausetheyhavelongerureters(thelongtubesconnectingthekidneytothebladder)thanrightkidneys.Indeceaseddonations,eitherkidneymaybeused.Theorganprocurementsurgeondissectsthekidneyfromthedeceaseddonoranditsattachmentsfromitssurroundings.Thekidneyisimmediatelyperfusedwithapreservationsolutioncomposedofhighpotassiumandothernutrientsandiscooleddowntodecreaseoxygendemand;thesestepskeepthekidneyashealthyaspossible.Intheoperatingroom,yourtransplantsurgeonwillplacethekidneyintoyourlowerabdomen.Heorshewillattachthebloodvesselsofthenewkidneytotheexternaliliacarteryandveininthegroin,andthenattachthenewuretertothebladder.Duringtheoperation,thesurgeonwillinsertaFoleycatheterintotheurethratothebladdertocollecturine.Theoldkidneysarenotusuallyremovedunlesstheyarechronicallyinfected,asinPKDpatientswithinfectedcysts.Otherwise,theydon’tnormallyposeathreattothepatient.

Figure7.5.TheNewKidneyinPlaceaftertheTransplantProcedure.Thetransplantedkidneyontherightsideofthebodyappearsontheleftinthe

figure,whichisfacingus.

PostoperativeCareAfterthethree-tofour-hourtransplantoperation,propercareandmonitoringbecomesessentialtomanagepostoperativepain,topreventrejectionofyourkidney,andtominimizeinfections.Yourrecoveryinthehospitalwilllast,onaverage,fivetosevendays,duringwhichtimeyouwillreceivenumerousmedicationstocontroltheaftereffectslistedabove.Initially,yourimmunesystemmustbeheavilysuppressedwithanti-rejectionmedications,whichreducesthelikelihoodofrejectingtheorganbutincreasesthelikelihoodofcontractinginfections.Tocounteractthispossibility,youwillreceiveantibiotic,antiviral,andantifungalagentstoreducethechancesofinfection.Youmusttakethesemedicationsexactlyasprescribed.Beforethetransplantyouwillhavetoldyourtransplantteamaboutanyothermedicationsyouaretaking,andtheteamwillmakeadjustmentsinmedicationstoavoidpotentiallyseriousdruginteractions.

Oncereleasedfromthehospital,youmustkeepdailyrecordsofyourbloodpressure,temperature,fluidintake,andurineoutput,andhaveyourbloodtestedregularlytodetectthepossibilityofinfectionorkidneyrejection.Youmustalso

eatahealthydietandexerciseregularlyonceyourincisionhashealed.Ahealthylifestyleisessentialduringthefirstyear(andbeyond)tokeepyourbodyinthebestshapepossible.Thepost-transplantcoordinatoratthecenterwilloutlinetheregimenyoumustfollow.Theneedforbloodtestsdiminishesovertime,asyourbodyacceptsthenewkidney.

Takingimmunosuppressantsoverthelongertermisthecornerstoneoftreatmenttopreventrejectionofyournewlytransplantedkidney.Yourtransplantsurgeon,dependingonthecenter’sprotocolandexperience,canprescribeseveraldifferentdrugs.Beforeandimmediatelyafterthetransplant,intravenousmedicationslikeanti-thymocyteglobulin(Thymoglobulin),daclizumub(Zenapax),andbasilixamab(Similect)maybeadministeredtoreducethechancesofrejection.Themainanti-rejectionmedicationscurrentlyprescribedforlong-termusearesteroidslikeprednisone(Deltazone),methylprednisone(Medrol),tacrolimus(Prograf),sirolimus(Rapamune,Rapamycin),mycophenolatemofetil(Cellcept),mycophenlicacid(Myfortic),andcyclosporine(Neoral,Gengraf).Cheapergenericmedicationsmaybeavailable;ifyoudesiretousethem,talkwithyourtransplantteam,whomustapprovetheuseofgenericmedications.

Anestimated10to40percentoftransplantrecipientsexperienceacuterejectionduringthefirstsixmonthspost-transplant.However,withtime,thebodyacceptsthekidneyandthedosesofimmunosuppressantswillbereducedtomaintenancedoses.Ifacuterejectiondoesoccur,short-termtreatmentwithhighdosesofimmunosuppressantmedicationsisadministered,andadjustmentswillbemadetothemaintenancedosesofthesedrugs.Ifacuterejectionoccursnumeroustimes,thekidneymayundergochronicrejectionbythebody,whichcanleadtothelossoffunctionoverthelongterm.

Immunosuppressantdrugshavemanysideeffects.Becausetheysuppresstheimmunesystemtopreventrejection,thebodybecomesmorepronetoinfectionsofalltypes,includingbacterial,viral,andfungalinfections.Duringthefirstsixmonthsaftertransplant,immunosuppressionisatitshighestlevel.Toreducetheriskofinfectionduringthistime,doctorswillprescribeseparatedrugsforeachthreat,likesulfamethoxazole/trimethoprim(Bactrim)forbacterialinfectionslikepneumonia,acyclovir(Zovirax)forviralinfectionslikeherpes,valganciclovir(Valcyte)forcytomegalovirus(CMV),andclotrimazoltroche(Mycelex)forfungi,especiallyofthemouthandthroat.Ifyouhavenoinfectionsaftersixmonths,yoursurgeonwilldiscontinuethesemedications.

Immunosuppressantsmayincreaseyourriskofdevelopingcancer,especiallylymphoma.Peopletakingimmunosuppressantsarealsoatahigherriskof

lymphoma.Peopletakingimmunosuppressantsarealsoatahigherriskofdevelopingskincancers.Carefulmonitoringisrequiredtodetectcancerearlyandtoinitiateearlytreatment.Themonitoringforcancerincludesperiodicassessmentsofwhetherlevelsofviruses,normallyundercontrolbytheimmunesystem,areelevated.ThisisespeciallytruefortheEpstein-Barrvirus,whichcancauselymphomas.Youwillneedregularlyscheduleddiagnostictestslikemammograms,PAPsmears,colonoscopies,andskincancerscreenstopreventcancersfromdevelopingoutofcontrol.

Anothersideeffectofanti-rejectionmedicationsisdevelopingelevatedbloodlipids(hyperlipidemia),whicharehigherthannormalvaluesforcholesterolandtriglyceridesintheblood.Elevatedcholesterolandtriglyceridesareriskfactorsforheartdiseaseandstroke.Ifyouhaveelevatedbloodlipids,youwillneedtotakeadruglikeatorvastatin(Lipitor),simvastatin(Zocor),orfenofibrate(Tricor).Inaddition,youmusteatalow-fatdiet.

Steroidsposeadditionalcomplicationsfortransplantpatients.Aswehaveseenthroughoutthisbook,diabetesisthemajorcauseofkidneyfailure.Unfortunately,bothsteroidsandtacrolimuscancomplicatemanagementofType2diabetes.Peoplewhodonothavediabetesareatriskofdevelopingthediseasewhiletakingsteroids.Steroidsmayalsoincreaseyourriskofdevelopingosteoporosis.Osteoporosisresultsfromthelossofcalciumfromthebones,makingthemmorebrittleandpronetofracture.Ifyouhavebeenondialysis,youareprobablyfamiliarwiththisrisk,whichsteroidsmayonlyincrease.Fortunately,manytransplantcentersarenowprescribingsteroidsless.Atsomecenters,doctorseventuallyweantheirpatientsoffsteroidsaltogether.

Peopleawaitingatransplantareatahigherriskofdevelopinghypertensionbecausebloodpressuremaybedifficulttomanage.Afteratransplant,itiscommonforbloodpressurelevelstodeclinedramatically.However,someimmunosuppressantscanelevatebloodpressure,aswellasincreasetheriskforcardiovasculardisease.Yourcenterwillcloselymonitoryourbloodpressureforanysuddenincreasesordecreases.

Weightgainisacommonproblemwiththosereceivingatransplant.Insomecases,theweightgaincanbeasmuchas100pounds.Thisiscausedbytheimmunosuppressantmedications.Notonlydosomeofthemleadtofluidretention,theycanalsoinhibittheabilityofthebodytoburnfatdeposits.Althoughyouwillbeabletoeatwhateverfoodsyoulike,youmayfindthatyouwillhavetolimityourcaloricintake.IhavehadthisproblemsinceIhadmytransplant.Todealwithweightgain,inadditiontolimitingmyfoodintake,Iengageinarigorous,dailyexerciseprogramconsistingofstrengthtrainingandaerobicsthatkeepsmyweightundercontrol.Asanaddedbenefit,thisprogram

aerobicsthatkeepsmyweightundercontrol.Asanaddedbenefit,thisprogramhasalsokeptmybloodpressureandbloodglucoselevelsundercontrolwithouttheneedofanymedications.Beforeyoustartsuchanexerciseprogram,consultyourtransplantteamtoensurethatyouarephysicallyabletodoit.

Becausethefunctioningofonetransplantedkidneywillneverbeequivalenttotwonormalkidneys,yourcreatinine,bloodureanitrogen(BUN),andglomerularfiltrationrate(GFR)willbemonitored.Ifkidneyfunctionbeginstodeteriorateaftermanyyears,yournephrologistwillassesswhetheranyofthehealthproblemsthatyouexperiencedbeforeyourtransplant,likeanemiaandbonedisease(seechapter4),aresimilartothecurrentdecline.

Inspiteofpotentialcomplicationsaftertransplant,withanewkidneyyoucanexpectaconsiderableimprovementinyourqualityoflife.Youshouldhavenoproblemworking,traveling,andengagingintheactivitiesthatyouenjoy.Youmayfind,asmanytransplantrecipientsdo,thatreceivingakidneytransplantislikebeingbornagain.Youwillfeelsomuchbetterthatintimeyoumayforgettheworstexperiencesofkidneyfailure.Lifewillbeyoursforthetaking,butonlyaslongasyoucareforyournewkidneyandfollowalloftheinstructionsofyourtransplantteam.Remember,akidneytransplantisnotacurebutatreatment.

ClinicalTrialsParticipatinginaclinicaltrialisoneroutetoreceivingatransplant.Clinicaltrialsareresearchprojectsusinghumansubjectsandaredesignedtoanswerspecifichealthquestions.Mosttrialsassesswhetheranewmedicationorprocedurewillbeaneffectivetreatmentforpatientswithaspecificdisease.Inthecaseofkidneytransplants,numerousclinicaltrialsareunderway.Tolearnmoreaboutthem,visittheNationalInstitutesofHealth(NIH)ClinicalTrialswebsiteatwww.clinicaltrials.gov.

IbecameinterestedinclinicaltrialsmorethanayearbeforeIreceivedmykidneytransplant,whenIrealizedthatreceivinganewkidneymightnotbetheendoflivingwithkidneyfailure.Icouldbeunluckyandlosemykidneytorejectionorinfection.Therefore,Idecidedtofocusonfindingwaystomaximizethelong-termsuccessofmynewkidneyandtoreducethepossiblecomplicationsinducedbyimmunosuppressantdrugsbypossiblyenrollinginaclinicaltrialdesignedtodojustthat.

Aftertalkingtomytransplantcoordinatorandthesocialworkeratmydialysiscenter,IlearnedthatNIHhadongoingclinicaltrialsthatmatchedmyinterest.IcalledthetransplantcoordinatoratNIHandtoldherofmyinterestinparticipatinginatrial.Afterthoroughlyreadingtheresearchprotocols,Imade

participatinginatrial.Afterthoroughlyreadingtheresearchprotocols,Imadeanappointmenttomeetwiththetransplantcoordinatorandtheprincipalinvestigator.

Thegoalofmyfirstvisitwastogatherinformationabouttheprogramandthecredentialsoftheresearchers.Beingaresearchermyself,Iwantedtodelveintothescientificrationaleoftheirresearch,theiraccomplishmentsanddisappointmentswiththeirresults,andthepossiblerisksofenrollinginthetrial.Iscouredthepublicationsthattheyprovided.

Thesciencebehindtheirresearchandthetrialmadeagreatdealofsensetome.Theresearchersdesignedtheprotocoltomakethebodytoleranttothepresenceofaforeignorgan,therebyreducingthelikelihoodofrejection.Indoingso,atransplantrecipientwouldneedfewerimmunosuppressantdrugstoavoidrejection.Astorisk,theyhadlostnokidneysduetorejectionsinceNIHestablishedtheirtransplantinstitutein1999.Onlytwokidneyswerelostbecauseofviralinfections.

Knowingthesestatistics,IdecidedthatIcouldaccepttherisksandthattheclinicaltrialwasworthconsideringseriously.Fromwhatthedoctorstoldme,Iwasconvincedthatparticipatinginthetrialwouldnotadverselyaffecttheoutcome,comparedtostandardcareatatraditionaltransplantcenter.Asadditionalinsurance,Iaskedmynephrologisttocalltheprincipalinvestigator,whowasalsothetransplantsurgeon,toassessforherselfthepotentialrisksIwouldbetaking.Aftertalkingtothesurgeon,mynephrologistfeltthatIwouldnotbetakinganyadditionalrisksifIparticipated.Afterdoingmyownresearchandwiththesupportofmynephrologist,Idecidedtoenrollinthestudyanddidnotlookback.MypreparationforthetransplantIreceivedthroughtheclinicaltrialmirroredthepreparationdescribedearlierinthischapter.

Morethansixyearshavepassedsincemytransplant,andIhaveexperiencednorejectionepisodesandnosignificantinfections.Iamcurrentlytakingasmalldoseofonlyoneimmunosuppressantdrug.Moreover,Inolongerhavehighbloodpressure.Asaresultoflivingahealthylifestyle,Ihavebeenabletotravelallovertheworld,whichiswhatIenjoydoing.

Afterparticipatinginthisclinicaltrial,Iarrivedatseveralconclusionsaboutthebenefitsanddrawbacksofclinicaltrials,andIhavesomeideasabouthowtodecidewhethertoparticipateinone.Herearesomeissuestoconsider.

HowFarAlongIstheResearch?

Clinicaltrialsprogressinseveralphasesbasedonthenumberofsubjectsandthequestionsasked.PhaseItrialstendtohavefewerparticipantsandaredesigned

questionsasked.PhaseItrialstendtohavefewerparticipantsandaredesignedtodeterminethesafetyofthemedicationandrangeofdosesforuseinfuturetrials.Ifthemedicationisnew,withfewstudiesdoneinhumans,thegreatestriskcouldoccurduringPhaseItrials.OtherPhaseItrialsaredesignedtotestdrugsapprovedbytheFoodandDrugAdministration(FDA)foroneapplication,butresearcherswanttoevaluatetheiruseforanewapplication,perhapsforadiseaseforwhichthemedicationwasnotoriginallyintended.Inthiscase,participationinaPhaseItrialislessrisky,becausemuchofthedrugsafetytestinghasalreadybeendone.

PhaseIItrialsenrollmoresubjects,typicallyafewhundred.Atthisstage,efficacyandsafetybecomeimportantfactors.IchosetoparticipateinaPhaseIItrialbecausetheexperimentaldrugshadalreadybeenFDAapprovedforanotherapplication.Inaddition,theresearchershadgoodevidencethattheprotocolhadahighchanceofsuccess.

PhaseIIItrialsmayinvolvethousandsofpatients,andareconductedinmultiplecentersaroundthecountryandeventheworld.Bythispoint,safetyandefficacyhavebeenreasonablyestablished.Therisksaresubstantiallyreduced,butdeathorlessseverecomplicationsmayoccurinasmallpercentageofparticipants.

UnderstandingtheProtocol

Scientificresearchisoftendifficulttounderstand,especiallyforpeoplewhodonothavetraininginscience.Thescientificjargoncansoundlikeaforeignlanguage.AlthoughIunderstoodmuchofit,thereweretermsandresearchissuesthatwereunfamiliar.Anyoneparticipatinginaclinicaltrialhastherighttounderstandfullywhatthestudyinvolvesandwhatrisksarepossible.Keepaskingquestionsuntilyouaresatisfiedthatyouunderstandallofthepotentialrisksandrewards.Ifnecessary,askyourdoctorsforhelp.Ifoundthatmynephrologist’sinputhelpedallayanyremainingconcernsIhadaboutenrolling.

AdvancingMedicalResearch

Manypeopledecidetoenrollinaclinicaltrialbecauseconventionalmeansoftreatmenthavenotbeensuccessful.Theirparticipationinaclinicaltrialmaybetheironlyhopeforsurvival.Goodcandidatesforkidneytransplantstypicallydonotfacethisdilemma.Standardtransplantprotocolsareacceptableandaregenerallypreferabletoremainingondialysis.

Eveninclinicaltrials,theuseofmedicationsorproceduresoccursonlyafterrigorousresearch,firstwithexperimentalanimalsandthenwithhumansubjects.

Toadvancethisresearch,humanvolunteersareneeded.Ifpeopledidnotparticipateinclinicaltrials,therewouldbenonewdrugs!Peoplewhoparticipateinclinicaltrialsrealizethattheyaremakingasignificantcontributiontoimprovingthehealthoftheirfellowhumansandperhapsthemselves,too.Theprospectofmakingadifferencegavemeconsiderablesatisfaction.Ihadworkedinmedicalresearchformorethanthirtyyears,andmyparticipationgavemeanopportunitytocontinuecontributing.Youmayfeelthesameway.

MedicalInsuranceandCare

Anotherbenefitofenrollinginaclinicaltrialiscost.Peoplewhoenrollinatrialreceivefreetreatmentandhealthcarerelevanttothestudy,whichmaybeespeciallyattractiveforpeoplewhodonothavemedicalinsurance.AlthoughMedicarewillcovermuchofthecostofatransplant,theremainingcostscanstillbesubstantial.Atransplantrecipientcansaveaconsiderableamountofmoney,especiallyforprescriptiondrugs,byparticipatinginatrial.EventhoughIhadagoodhealthinsurancepolicy,participatingintheclinicaltrialstillsavedmemoney.

MyExperienceMytransplantsurgeoncalledmeat3:30onemorningtotellmethatmytimehadcometoreceiveanewkidney.Iwashappyyetapprehensiveaboutwhattoexpect.EventhoughIhadpreparedforthisday,nowtheideaofatransplantchangedfromtheabstracttoareality.

At6:30a.m.,IdrovetoNIH,whereforseveralmorehoursIwaitedforthelabtocompletethefinaltestingtomakesureIwascompatiblewiththekidney.Atabout11:00,thenurseplacedanintravenouslineintomyarmandgavemeasedative.Asthenurseswheeledmedowntotheoperatingroom,thesedativesmusthavekickedin,becauseIdonotrecallgettingthere.Iawokeseveralhourslaterintherecoveryareawithanewkidney.

Forme,theimmediatepostoperativeissueswererecoveringfromtheanesthesiaandmanagingpain.Ifindgeneralanesthesiadisorienting.Inthepast,Ihavehadvisualandsometimesauditoryhallucinationsforseveraldaysafterreceivinggeneralanesthesia.AlthoughIfoundthisdisconcerting,Iknewthattheywouldgoaway.Anadditionalcomplicationformewasgettingmybowelstofunctionproperly,whichtookseveraldays.Paincanbemanagedwithamorphinedriporbyself-administrationusingapump,whichcontrolstheamount,maximumdose,andappropriateintervalsofintake.(Morphine,unfortunately,tendstocauseconstipation,whichfurthercomplicatesthebowelproblem.)Thankstoamorphinedrip,Ihadnosignificantpostoperativepain,

problem.)Thankstoamorphinedrip,Ihadnosignificantpostoperativepain,eventhoughIhadaneight-inchincisioninmylowerabdomen.

Aspartoftheclinicaltrial,Ireceivedamedicationjustaftermytransplanttofurtherreducemychancesofrejectingmykidney.Inadditiontoanti-rejectionmedications,mydoctorsprescribedanti-thymocyteglobulin(Thymoglobulin)forseveraldaystodepletetheT-cellsresponsibleforrejection.ThistreatmentkeptmyT-cellcountlowforalmosttwoweeks.Intheprogram’sexperience,theimmunesystemsofpatientsgivenanti-thymocyteglobulinwerelessresponsivetoaforeignkidney,comparedtoastandardtreatmentprotocol.Forme,anti-thymocyteglobulinhadastrangesideeffect.Myhandsitched,andthentheskinpeeled.Theywereunsightlyforawhile,buttheyreturnedtonormalafterthelastdoseofthedrug.

Beforetransplant,myhighbloodpressurewasdifficulttocontrol,evenwithhighdosesofthreedifferentbloodpressuremedications.Aftermytransplant,mybloodpressuredroppedtothepointwhereIneededonlyonemedication.Aftersixmonths,Inolongerneededanybloodpressuremedicationatall.Morecloselycontrolledbloodpressurewasamajorbenefitofhavingakidneytransplant.

Likemanypeoplereceivingkidneytransplants,Ihadelevatedbloodlipidsbeforereceivingatransplant.Infact,mybloodlipidswereinitiallysohighaftermytransplantthatthenursewhodrewmybloodcouldseethefatinthesample.ItwasfortunatethatIdidnothaveaheartattackorstroke.Atthetime,Iwastakingsirolimusandtacrolimusasmyanti-rejectionmedications.Totreatthehighbloodlipids,mydoctorstookmeoffthesirolimus,whichwasidentifiedasthecause.Withpropertreatment—inmycase,withfenofibrate(Tricor),pravastatin(Pravachol),andfishoilcapsules—Ihavemaintainednormalbloodlipidlevels.

AnothercomplicationIexperiencedwascontractingtheEpstein-Barrvirus.Althoughtheleveloftheviruswashigh,Ihadnosymptoms.Still,mydoctorswereconcernedenoughtocallinaspecialistonthevirustoexamineme.Inhisopinion,Irequirednospecifictreatment,butmydoctorswereinstructedtomonitortheviruscarefully.BecausetheybelievedthattheelevatedlevelofthevirussuggestedthatIwasexcessivelyimmunosuppressed,theydecidedtolowermydosesofanti-rejectionmedications.

ReducingtheamountofimmunosuppressantsIwasreceivingcouldhaveplacedmykidneyatriskofrejection.Inmycase,loweringthedoseofmymedicationnotonlyreducedthelevelofthevirusbutalsoloweredmybloodcreatinine.Ifmybodywererejectingmykidney,mybloodcreatininewould

creatinine.Ifmybodywererejectingmykidney,mybloodcreatininewouldhaverisen.Becauseanti-rejectiondrugscandamagethekidney,lessimmunosuppressionactuallyhelpedinmycase.

Myexperiencewithaclinicaltrialmaynotbetypical.Beingpartofanexperimentalprogramtoreducetheamountofimmunosuppressionneeded,ratherthangettingatransplantunderstandardcare,probablyreducedmyriskofrejectionowingtoviralinfections.Afriendofminediedfromcomplicationsoflymphomaresultingfromahighdegreeofimmunosuppression.Inhiscase,helosthiskidneyandpassedawayafteradialysistreatment.ThiswasanotherreasonwhyIchosetoenrollintheclinicaltrial.

Sixmonthsaftermytransplant,Inolongerhadtotaketheantimicrobialmedicationsandtookonlyalowdoseoftacrolimusasmyimmunosuppressant.Atthatpoint,Ifeltgreatandstartedcreatingmynewlife.Todeterminewhetheraclinicaltrialisrightforyou,consultyournephrologistforhelp.

Aswelearnedearlierinthechapter,kidneytransplantationshaveveryhighratesofsuccess.MostofthetransplantrecipientswhomIknowpersonally,regardlessofwhethertheyreceivedthemthroughastandardprotocoloraclinicaltrial,haverespondedverywelltotheirneworgans.Somehadcomplications,buttheyeventuallyhealedandareenjoyinglifetothefullest.Socanyou.Ifyouhavenosignificantcomplicationsafteryourtransplant,you,too,canliveanormallife,andkidneyfailurecanbecomeadistantmemory.

8FUTURETREATMENTOPTIONS

ThroughoutthisbookIhavediscussedtreatmentsthatarecurrentlyavailableforpeoplewithkidneyfailure.Ihavealsodiscussedoptionsfortreatingthecausesofkidneyfailure.Thischapterlooksaheadtowhatthefuturemayholdintermsofnewtreatmentsforpeoplewithfailingkidneys.

Inthe1950s,whenmymotherconfrontedkidneyfailurecausedbypolycystickidneydisease(PKD),therewerenotreatmentsforhypertension,anemia,orkidneyfailureitself.Neitherdialysisnortransplantationwasreadilyavailableforpeoplewithkidneyfailurefromanycause.Atthetime,kidneyfailurewasadeathsentence.

Overthelastfivedecades,however,dedicatedresearchhasyieldedmanynewtreatmentoptionsforpeopleatriskforkidneyfailure.Notallofthesenewtreatmentsareoptimal,andtheirsideeffectssometimesimpedequalityoflife.Forexample,althoughkidneytransplantationisthetreatmentofchoiceforkidneyfailure,theavailabilityofadonorkidneyisuncertain,andtheunderlyingdiseasemighttakeitstollwhilethepersoniswaitingforatransplant.Inaddition,onceatransplanthasbeenperformed,thesideeffectsofimmunosuppressantdrugscanbelifethreatening.Iftheprospectofkidneyfailureisinyourfutureorinyourchildren’sfuture(thatis,ifyourfamilyhasastronggeneticpredispositionforkidneyfailure),lookingtentotwentyyearsahead,athowthenextgenerationmightfare,maygiveyouhopeaboutthefutureoftreatment.Althoughsomeofthisdiscussionisspeculative,theprospectsareplausible.Onlytimewilltellifanyofthesepromisingnewapproachestotreatmentcometofruition.

NewMedicationsTheHumanGenomeProject,whichsequencedthegenesoneachofthetwenty-threehumanchromosomes(seechapter3),mayallowscientiststofindtheproteinsthateachgenemakes.Withacomprehensionoftheroleoftheseproteinsinoperatingthebiochemicalreactionsofourcells,wemaybegintounderstandtheunderlyingdefectsthatcausedisease.Researchisunderwaytoidentifypotentialtargets,likereceptorsorenzymesinvolvedinanabnormalresponse.Oncethetargetshavebeenidentified,researcherscandevelopnew

medicationstoworkeffectivelywiththosetargets.Historically,developingamedicationinvolvesstudyingitsoverall

effectivenessandsafetyinapopulationofpeoplewithadisease,becausenotallpeoplereacttothedruginthesameway.Instudypopulations,responsesvary,andresearchersuseanalyticaltoolstodecidewhetheradrugwillbeusefulandsafeintheclinicontheaverage.Becausemanygenescouldbeinvolvedwithadisease,theresponsetoaspecificdrugbyaspecificpatientcouldbedifferentfromhowtheaveragepersonreactstothedrug;forexample,thepatientmayreactdifferentlyonthebasisofthedrugtargetorthewaythepatient’sbodyprocessesthedrug.

Inthefuture,doctorsmaybeabletopredicthowanindividualwillrespondtotreatment,resultinginindividualizedhealthcarethatistailor-madetoaperson’sspecificcharacteristics,notjusttohowpeopleonaveragerespondtoamedication.Inthefuture,healthcaretreatmentsmaybemodifiedonthebasisofaperson’sgeneticallymediatedresponsestoanumberofmedications,someofwhichmaybeeffectiveandsomenot.Thisnewapproachtotreatmentiscalledpharmacogenetics.Dependingonthecondition,thispromisingfuturetreatmentcouldanalyzeaperson’sgeneticcodetodeterminewhetherhergeneticattributessupporttheuseofaparticulartreatment.

Pharmacogeneticsmayalsoyieldinformationaboutthetargetofthemedicationandhowthebodybreaksdownthedrug.Forexample,thelivermetabolizesdrugsusingenzymes,whichhavedifferentactivities,basedonthevariantsofthegenesinvolved.Identifyingwhichgeneticvariantsofliverenzymesapersonhascouldhelpdoctorsprescribedrugsthataremostlikelytoworkaccordingtothatperson’sgeneticmakeup.

Althoughinitsinfancy,pharmacogeneticshasalreadyledtothedevelopmentofbettertreatmentsforsomediseases.Ithasbeenknownsincethe1950sthatcertaingeneticvariantsinanumberofenzymesthatmetabolizedrugsinthelivercanenhanceorreducetheireffectiveness.Morerecently,thetreatmentofhepatitisChasbeengreatlyimprovedbytheobservationthataproteinknownasartificialinterferonismoreeffectiveinpatientswithaparticulargeneticvariantthaninpeoplewithoutit.

Whetherapharmacogeneticapproachwillyieldimprovedtreatmentsforkidneydiseaseremainstobeexplored.Abetterunderstandingofthemechanismsunderlyingdifferentdiseasesismorevaluablefortreatingsomeillnesses,butnotall.Becauseaspecificdiseasecanbeassociatedwithmanyvariationsinthegeneticcode,asisthecasewithdiabetes,anyspecificvariation

mightcontributeagreatdeal—orverylittle—totheexpressionofthedisease.Thus,pharmacogeneticsholdsthemostpromisewithdiseasesinwhichthereisvariationofonlyafewgenescontributingtotheexpressionofthedisease.

Individualizedtreatmentbasedonaperson’sgeneticcodeisnotafar-fetchedidea.Thecostofperformingthesequencinghasplummeteddramaticallyinrecentyears.Sequencingoneperson’scompletegenomewillprobablycostaslittleas$1,000orpossiblylessinthefuture.Inthefuture,too,sequencingachild’sentiregenomeatbirthmaybecomearoutineprocedure.Becauseaperson’sgenomedoesnotchangeovertime,itwouldbenecessarytosequenceeachperson’sgenomeonlyonce,andthereforethiswouldbeaone-timeexpense.Inthefuture,aswebeginunderstandinghowandwhengenesturnonandoff,itmaybepossibletodeterminewhichgenesareoveractiveorunderactiveinadiseasestateandtotailorthetreatmenttotheprocessthataspecificgenemediates.Currentlyitispossibleindiseaseslikecancertopredicttheresponsetoaparticularformoftreatmentbasedonacertaingeneticcharacteristicofthepatient.

Thereisadownsidetogenomesequencingandtoknowingaperson’spredispositionstospecificdiseases.Foronething,apredispositiontoadiseasedoesnotnecessarilymeanapersonwillgetthedisease.Manydiseasesdeveloponlywhenapersonwhohasthegenesthatmakehimsusceptibletothediseaseencounterssomethingintheenvironment,likeavirus,whichturnsthedisease“on.”Somecriticsarguethatgeneticsequencingcouldcausepeopletoworryneedlessly,becausetheymightneverdevelopadisease,eventhoughtheirgenesindicatethattheyhavethepotentialtodevelopthedisease.Thereisalsosomeconcernthatworriedindividualswillgetunnecessarymedicalprocedurestomonitorfordisease.Also,evidencethatapersonisatriskforaspecifichealthconditionmightleadinsurersoremployerstodiscriminateagainstthatperson.Inanefforttocombatthisconcern,theGeneticInformationNondiscriminationActwassignedintolawin2008;thisActspecificallyforbidssuchdiscriminationonthebasisofgeneticinformation.Inaddition,thepassageofthePatientProtectionandAffordableCareActin2010willprohibitthistypeofdiscriminationbeginningin2014.

DialysisPeoplewhohavebeenondialysisknowthatitisanoftenunpleasanttreatmentforkidneyfailure.Althoughdialysiskeepsusaliveandcanimproveourqualityoflife,itcanbeuncomfortableandhasnumerousotherdrawbacks.Aswelearnedinchapter6,bothperitonealdialysisandhemodialysishavetheirpros

andcons.Peritonealdialysisallowsustoperformourowntreatmentbutcanbe

inconvenientintermsofwherewecanperformexchanges.Inaddition,peritonealdialysiscausesweightgainandlossofprotein,andcarriestheriskofperitonitis.Hemodialysismustbeperformedonaspecificschedulethatmaynotbeconvenient,especiallyconsideringthedemandsofemployment.Peopleonhemodialysismayexperiencesideeffectslikelightheadedness,nausea,bleedingfromthefistulaorgraft,andinfections.Tohavehemodialysis,apersonmusttakeagreatdealoftimeoutofhisnormalscheduletomakeclinicvisitsseveraltimesaweek.Regardlessofwhatformofdialysiswechoose,thedrawbackscantakeatoll.

Currentlyunderstudyandinuseinsomecentersisanapproachinvolvingmorefrequenthemodialysistreatments.Currentpracticesforhemodialysisrequiredialysisthreetimesaweek,eitherinacenterorathome.Becauseintermittentdialysisislessefficientthancontinuousdialysis,newerapproachesinvolveshorter,morefrequent(daily)treatments.

Avariationofthisapproachisnightlyhomehemodialysis,inwhichpatientsdialyzewhiletheysleepusingaslowerflowrate,withatypicaltreatmentlastingsevenhours.Proponentsofnightlyhomehemodialysisclaimthatpatientsmaintainbettercontroloftheirbloodchemistries,havefewerproblemswithanemia,havebetterbloodpressurecontrol,andspendlesstimeinthehospital.1Thecurrentnumber,organization,andlocationoftechniciansandnursesmaynotbeadequatetoprocesstheincreasedworkloadofdailytreatments,eventhoughthisapproachmightbenefitmanypatients.Currently,Medicareandhealthinsurancecompaniesdonotroutinelycoverthesetechniques,butextratreatmentsmightbejustifiedonthebasisofimprovedpatientoutcomes.Anotherdrawbacktonightlyhomehemodialysisisthatitcanbedifficulttosecuretheneedlesintheaccesstoavoidseriousandpotentiallylife-threateningbleeding.

Alsounderdevelopmentarewearablehemodialysismachinestoallowformorefrequentdialysis.2Thesedesignsusesmallmini-pumpsanddialyzersbuthavesorbentsystems,whichabsorbthedialysateandcleanandrecirculateit,reducingtheneedforalargefluidsource.Stillintheearlystagesofdevelopment,wearablehemodialysisunitshavethepotentialtoincreasethequalityoflifeofpatientsbyimprovingtheirmedicaloutcomesandreducingtheamountoftimetheyspendindialysiscenters.

Finally,artificialfiltersordialyzersthataremoreefficientmightimprovethemedicalresultsofhemodialysis.Becausethecruxofhemodialysisisthe

dialyzer,improvingitsfilteringcapabilities,whilesparingtheintegrityofredbloodcellsandreducingstressonthebody,couldimprovemedicaloutcomesforpatients.Somenewerdialyzersarebetterabletoretainproteinandremoveexcessphosphate.Perhapsdialyzersofthefuturewillbeevenmoreeffective.

TransplantationReceivingakidneytransplantisagreatgiftoflife,whetheryouwereondialysisorwerefortunateenoughtogetanewkidneybeforeyourkidneyscompletelyfailed.Thefreedomthatatransplantgivesisimmeasurable.Beingabletoreturntomynormalactivitiesmadeagreatdifferenceinmyqualityoflife.Althoughyoumusttakemedicationsfortherestoftheusefullifeofyourkidney,itisfarbetterthanbeingtetheredtoadialysismachine.

Aswesawinchapter7,thebiggestriskassociatedwithorgantransplantsisrejection.Becausethebodyperceivesthenewkidneyasaforeigninvader,theimmunesystemwillattempttodestroyit.Therefore,aspartofthepost-transplantationcareregimen,transplantrecipientstakedrugsthatsuppresstheimmunesystem.Theimmune-suppressingmedicationsavailabletodayarequitegoodinpreventingrejection.However,thereareseriouspotentialsideeffects.Asuppressedimmunesystemincreasestherisksofcontractinginfectionsandsomeformsofcancer.Someoftheseconditionscanbelifethreatening.Inaddition,therisksofdevelopingdiabetes,cardiovasculardisease,andosteoporosisincrease,especiallywhentakingsteroids.

Apossiblesolutiontothesecomplicationsmaybethedevelopmentofimmunosuppressantstargetedtothepartoftheimmunesystemresponsibleforrejection.Now,physiciansusemedicationsthatsuppressallcell-mediatedimmunefunctions.Inthefuture,newdrugsmighttargetimmunefunctionsthatrelateonlytotransplantedorgans.Thatapproachwouldputmuchlessstressonthebody.

Anotherapproachcurrentlyunderstudybutnotyetwidelyusedisloweringtheresponseoftheimmunesystemtothepresenceofaforeignorgan.IparticipatedinsuchastudywhenIreceivedmytransplant(seechapter7).Thepremiseinvolveddepletingthecellsthatcauserejection—T-cells—forabouttwoweeks,whichallowedenoughtimeformybodytogetusedtothenewkidney.Asaresult,Ineededfarlessimmunosuppressionthanisusuallyrequired,therebyreducingmyriskofdevelopingthecomplicationsthatoftenresultfromthestandardprotocol.Withfurtherresearch,thisapproachcouldbetailoredtotheindividualpatient.Eventually,itmaybepossibletoavoid

rejectionalltogether.Oneintriguinglineofresearch,calledxenotransplantation,involves

assessingwhetherkidneysfromanimals(likepigs,whichhavekidneysthatarestructurallysimilartohumankidneys)couldbeusedasdonorsforhumantransplant.Althoughitwouldseemalmostcertainthattherecipient’sbodywouldrejectthekidneyfromanotherspecies,scientistshopeonedaytogeneticallyengineerpigssothepigs’kidneysareimmunologicallylessreactiveorinactiveinahumanpatient.Anotherdifficultywithxenotransplantationistheriskthattheanimal’sorgansmightcontainretro-virusesthatcouldinfectarecipient.Furtherresearchwillbeneededtofindoutwhetherxenotransplantationwillbeaviabletreatmentforkidneyfailureinthefuture.

Stemcellsmayprovetobeanotherpromisingavenuetoimprovingthesuccessratesoftransplantations.Stemcells,whentheyareintherightform,cantransformintoanycelltypeinthebodyundertheproperconditions;thus,stemcellssomedaymaybeusedtogrownewbodyparts,includingkidneys,forpeoplewhoneedthem.Stemcellscancomefromeitherembryoniccells(fromhumanembryosorhumanumbilicalcordblood)oradultcells.Althoughresearchersarestudyingstemcellsasprecursorsformakingspecializedcellstocorrectmanydiseases,themoralimplicationsofusingembryonicstemcellshavehamperedresearchforthispurpose.

Adultstemcells,especiallywhentheyaretakenfromthesamepersonwhoneedstreatment,havegreatappealinthetreatmentofdisease.However,adultstemcellshavenotyetshowntheirpromiseasbeingagoodsubstituteforembryonicstemcells.Recentstudieswereperformedthatsuccessfullyconvertedadulthumancellstoembryonicstemcellsandthendeliveredthemtothecorrecttargetsusingviruses.3Unfortunately,however,theembryonicstemcellshadhighratesofcancerdevelopment.Inveryrecentresearch,scientistswereabletoavoidusingavirusandsuccessfullyconvertedtheadultcellsintoanembryonicstate.4

Evenifeitherembryonicoradultstemcellscanbemanipulatedtomakeanytypeofcellwewant,weknowverylittleaboutthecomplexprocessthebodyusestocreateanorganfromthosecells.Duringfetaldevelopment,variousgenesturnonandoffatvarioustimestoconstructeachorgan.Asonecanimagine,theprospectofre-creatingtheorgandevelopmentprocessoutsidethewombisdaunting,asitwouldrequiretakingskincellsorothertypesofcellsfromapersonneedinganeworgan,likeakidney,convertingthecellsthroughaseriesofstepsintoakidney,andthentransplantingitintothepatient.Becausethekidneywouldbegeneticallyidenticaltothepatient,noimmunosuppression

kidneywouldbegeneticallyidenticaltothepatient,noimmunosuppressionwouldberequired.Onlytimewilltellwhethersuchanapproachtotransplantationwilleverbepossible.

Scientistsarepursuingallofthesedifferentavenuesofresearchatthesametime.Anyonewhoreadsthenewspaperorlistenstoradioorwatchestelevisionknowsthatbreakthroughsinmedicaltreatmenthappenallthetime.Onedayaneweditionofthisbookwillbeneeded,becausethetreatmentofkidneydiseasewillhaveadvancedsofarthatcurrenttreatmentsareoutdated.

Ilookforwardtowritingthatnewedition.

EPILOGUE

Itcanbedevastatingtoreceiveadiagnosisoffailingkidneys.Itcanbedauntingtoanticipatewhatliesahead,includingthedifficultiesoftreatment.Educatingyourselfaboutthedecisionsyoumustmake,aswellasusingallthetoolsavailabletoyou,willhelpyoumanagetheprocess.Ultimately,itwillbeuptoyoutodecidehowhardkidneyfailurewillbeforyou.

ThroughoutthisbookIhaveemphasizedtheimportanceoftakingresponsibilityforyourhealth.Acceptingthatyouareprimarilyresponsibleforyourhealthwillempoweryouasyoufacetheprospectofkidneyfailure.

Younowhaveagreatdealofinformationabouthowtopreventorpostponekidneyfailure.Itistimetostartimplementingwhatyouknow.Forsomeofyou,theproblemmayseemfarinthefuture,andperhapssecondarytotheotherprioritiesoflifethatcompeteforyourattention.However,thisisnotimetobeindenial.Nopriorityismoreimportantthanyourlife.Withoutyourhealth,nothingelsewillmatter.Ilearnedthatlessonwhenmykidneysfailed.Youhaveachoice:takeactionnow,andpreventorpostponetheproblem,orsuffertheconsequencesofinactioninthefuture.

Takecontrolofyourhealth.Nooneshouldbemoremotivatedthanyouaretoimproveyourfuturequalityoflife.Yourfamilyandfriendscanhelpyou,butunderstandthattheyhaveonlysomuchtimeandenergytolend.Findwaystohelpyourselfanddonotdependtotallyonothers,notevenyourdoctors.Yourdoctorsmaygivethebestmedicaladvice,buttheyarenotresponsibleforimplementingtheiradvice.Youare!Usetheadviceinthisbook,andfindideasofyourownthathelpyouwithyourdailyactivities.

Iknowfirsthandhowtoughitcanbetotakecareofyourselfwhenyouaresick.Withlittleenergy,Ihadgreatdifficultyevengettingupinthemorning,letalonetakingcareofroutine,dailytasks.Butonmanydaysyouwillbewellenoughtodoatleastsomeofthemostimportantthingsthatrequireyourattention.Weallmakeoccasionalbaddecisionsorfeeloverwhelmedaboutourhealthsituation.Trynottodwellonthesetbacks.Celebrateyouraccomplishmentsandpushasideyourfailures.

Kidneyfailureisaseriouscondition.Butwithcommitment,patience,andpracticeyoucanmakeit.Alongtheway,createthelifeyouwant.

Remember:

Remember:

Movequicklythroughdenialandfaceyourdiseasedirectly.Beyourownadvocate.Believeyourlifewillimprove.Takethelongview.Remainoptimisticandgiveapositivespintoeverything.Knowyourprioritiesandsticktothem.Bewillingtotakerisks.Askforhelp,butdon’tdependonit.Keepyoursenseofhumor.

NOTES

Chapter1·UNDERSTANDINGKIDNEYFAILURE1.U.S.RenalDataSystem,USRDS2010AnnualDataReport:AtlasofEnd-

StageRenalDiseaseintheUnitedStates(Bethesda,MD:NationalInstitutesofHealth,NationalInstituteofDiabetesandDigestiveandKidneyDiseases,2010).Chronickidneyfailureoccursinstagesovermanyyears.ESRDisthefinalstageandrequirestreatment,eitherdialysisortransplantation.

2.E.Kübler-RossandD.Kessler,OnGriefandGrieving(NewYork:Scribner,2005).

Chapter3·WHYKIDNEYSFAIL1.Obesitywasmeasuredbybodymassindex(BMI)weightinkilograms

dividedbythesquareofheightinmeters.ABMIgreaterthan25isconsideredoverweight,over30asobese,andover40asmorbidlyobese.

2.http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm.3.D.Alshuleretal.,“Genome-WideAssociationAnalysisIdentifiesLocifor

Type2DiabetesandTriglycerideLevels,”Science316(2007):1331–1336;E.Zegginietal.,“ReplicationofGenome-WideAssociationSignalsinUKSamplesRevealRiskLociforType2Diabetes,”Science316(2007):1336–1341;L.J.Scottetal.,“AGenome-WideAssociationStudyofType2DiabetesinFinnsDetectsMultipleSusceptibilityVariants,”Science316(2007):1341–1345.

4.M.A.Lazar,“HowObesityCausesDiabetes:NotaTallTale,”Science307(2005):373–375.

5.B.E.Wisseetal.,“AnIntegrativeViewofObesity,”Science318(2007):928–929.

6.G.WolfandF.N.Ziydeh,“MolecularMechanismsofDiabeticRenalHypertrophy,”KidneyInternational56(1999):393–405.

7.A.B.Weder,“GeneticsandHypertension,”JournalofClinicalHypertension9(2007):217–223.

8.T.Steinman,“DiagnosingPKD,DeterminingOptions,”NephrologyNews&Issues,March2006.

9.J.J.Granthametal.,“VolumeProgressioninPolycysticKidneyDisease,”

NewEnglandJournalofMedicine354(2006):2122–2130.

Chapter6·DIALYSIS1.U.S.RenalDataSystem,USRDS2010AnnualDataReport:AtlasofEnd-

StageRenalDiseaseintheUnitedStates(Bethesda,MD:NationalInstitutesofHealth,NationalInstituteofDiabetesandDigestiveandKidneyDiseases,2010).

2.ThisdescriptionistheonethatIemployedwhenonperitonealdialysisusingsuppliesprovidedbyBaxterInternational,Inc.Suppliesfromothercompanies,likeFresenius,arealsoavailable.

Chapter7·TRANSPLANTATION1.ThissectionisadaptedfromanarticleIwroteforthePKDFoundation,

“WaitingforaKidneyTransplant,”PKDProgress18,no.2(2003):13.

Chapter8·FUTURETREATMENTOPTIONS1.A.S.Klinger,“MoreIntensiveHemodialysis,”ClinicalJournalofthe

AmericanSocietyofNephrology4(2009):S121–S124.2.C.Ronco,C.A.Davenport,andV.Gura,“TowardaWearableArtificial

Kidney,”HemodialysisInternational12(2008):S40–S47.3.J.Yuetal.,“InducedPluripotentStemCellLinesDerivedfromHuman

SomaticCells,”Science318(2007):1917–1920.4.J.Yuetal.,“HumanInducedPluripotentStemCellsFreeofVectorand

TransgeneSequences,”Science324(2009):797–801.

GLOSSARY

AcidosisBuildupofacidintheblood.AdrenalglandsSmallendocrineglandssittingatopthekidneysthatsecrete

aldosterone,promotingfluidandsaltretention.AlbuminuriaProteinintheurine.Urinewithhighamountsofproteiniscalled

macroalbuminuria,whileurinewithlowamountsiscalledmicroalbuminuria.

AldosteroneSeeAdrenalglands.AnemiaLowredbloodcellcount.AneurysmBallooningofamajorbloodvesselthatcanrupture,causingmassive

bleeding.Angiotensin-convertingenzyme(ACE)Enzymethatstimulatestheconversion

ofangiotensinItoangiotensinII.AngiotensinsystemSystemthatregulatesbloodpressurewhensalt

concentrationislow;reninreactswithangiotensinogen,whichstimulatestheconversionofangiotensinItoangiotensinII,whichthenconstrictsbloodvesselstoraisebloodpressure.

AntibodyAproteincreatedbytheimmunesystemtoattackanddestroyforeignentitieslikemicroorganismsandorganstransplantedfromotherpeople.

Antigen“Nametag”oncellsthatidentifiesthecellsasbelongingtoaspecificindividual.

AtherosclerosisBuildupofplaqueinbloodvesselsthatcancontributetohypertension.

Autosomaldominantpolycystickidneydisease(ADPKD)DominantformofPKD;achildhasa50percentchanceofinheritingthediseasefromanaffectedparent.

Autosomalrecessivepolycystickidneydisease(ARPKD)RecessiveformofPKD;achildhasa25percentchanceofinheritingthediseaseifbothparentsarecarriersofthemutatedgene,buttheparentsdonothaveARPKDthemselves.

BiopsyAprocedureinwhichasmallamountoftissueisremovedfromthe

bodyforinvestigationandtesting.BloodtypingThemeansfordeterminingoneperson’sbloodtypecompatibility

withanotherperson’sbloodtype.Compatiblebloodtypingisneededforkidneytransplantation.

Bloodureanitrogen(BUN)Ameasureofkidneyfunction.Ahighvalueindicatesdecliningkidneyfunction.

BonemarrowSofttissueinbonethatmakesredbloodcells.CalcidiolAnintermediateformofvitaminDintheproductionofcalcitriol.CalcitriolThemostactiveformofvitaminDthatthebodyuses.Itdoesnot

requireactivationbythekidneyandisoftengiventodialysispatientswhocannotmaketheirowncalcitriol.

CalciumAnimportantmineralinkeepingbonesstrongandamediatorinmanybiochemicalpathways.

CarbohydratesAgroupofsugarsandstarchesthatareasourceofenergyforthebody.

CarbondioxideThemainsubstanceinexhaledbreath.Intheformofbicarbonate,itneutralizesacidityintheblood.

CatheterAccesstoamajorvein.Cathetersareusedprimarilyfordialysisbutcanbeameansofadministeringmedicationsornourishment.Theycanalsobeusedtodrainurinefromthebladder.

CholecalciferolTheformofvitaminDtypicallyfoundinsupplements.Cholecalciferoldoesnothavetobeactivatedintheskin.SeeVitaminD.

ChromosomeStructurewithinthenucleusofthecellthathousesthegeneticcode.Eachcellcontainstwenty-threepairs.

ContinuousAmbulatoryPeritonealDialysis(CAPD)Aformofdialysisthatrequiresfourtofivemanualexchangesofabdominalfluidperday.

ContinuousCyclicPeritonealDialysis(CCPD)Aformofdialysisthatusesamachine(cycler)toperformexchangesduringthenight;somemanualexchangesareneededduringtheday.

CreatinineAmeasureofkidneyfunction.Creatinineiscompletelyfilteredbythekidney,makingitamoreaccuratemeasurethanBUN.Ahighvalueindicatesdecliningkidneyfunction.

CreatinineclearanceTheamountofcreatininefilteredbythekidneyand

passedintotheurine.Thisisthemostaccuratemeasureofkidneyfunction.CrossmatchThelasttestperformedtoavertrejectionofadonatedkidney.A

negativetestresultallowsthetransplantationtoproceed.Deoxyribonucleicacid(DNA)Blueprintforlife;DNAiscomposedoflong

stringsofnucleotidesequencescontainingtheinstructionsformakinguptothreeproteins.

DiabeticnephropathyDiabetes-inducedkidneyfailure.DialysateThesolutiondrainedfromtheabdomenduringaperitonealdialysis

exchange;also,thesolutionbathingadialyzerinahemodialysismachine.DialysisAmethodofcleansingthebloodofwasteproducts.DialyzerAfilterusedinhemodialysiscontainingtinyfilamentsbathedwith

dialysate;bloodpassesthroughthefilamentsandtoxinsdiffuseintothedialysate.

EdemaAccumulationoffluidinsofttissuesofthebody,especiallyinthelegsandankles.

ElectrolytesSalts,likesodiumandpotassium,whichcontrolmanyfunctionsinthebody.

ErythrocytesRedbloodcells,whichcarryoxygenthroughoutthebody.Erythropoietin(EPO)Ahormonemadebythekidneytostimulateproduction

ofredbloodcells(erythrocytes)inbonemarrow.ExchangeTheprocessinperitonealdialysisbywhichthedialysateisreplaced.FistulaAvascularaccesscreatedbyjoininganarteryandaveininanarmor

leg,usedforhemodialysis.GenesTheinstructionsformakingandrunningacell;genesarecomposedof

sequencesofDNA.Glomerularfiltrationrate(GFR)Ameasurementsimilartocreatinine

clearance,butcalculatedfrombloodcreatininetakingintoaccountageandrace.

GlomerulusAstructureinthekidneythatfiltersbloodofitswasteproducts.GlucoseThemainsourceofenergyinthebody.GraftAvascularaccesscreatedbyjoininganarteryandveintoeachendofa

Gortextube,usedforhemodialysis.

HematocritThevolumeofbloodcomprisingredbloodcells.HemodialysisFiltrationofthebloodwithamachinethatcirculatesblood

throughadialyzer.HemoglobinAproteininredbloodcellsthatcarriesoxygenthroughthebody.

Hemoglobinlevelscandropaskidneysfail.HeparinAbloodthinnerusedinhemodialysistoavoidclottinginthetubing

anddialyzer.HLAtypingThemeansfordeterminingoneperson’scells’immune

compatibilitywithanotherperson’scells.HLAtypingisusedformatchingdonorstorecipientsforakidneytransplant.

HomeostasisTheprocessofkeepingconditionsinthebodywithinanormalrange.

HormonesSubstances,likealdosteroneandleptin,actingonreceptorsthatchangephysiologicalfunction.

HyperlipidemiaElevatedbloodfatslikecholesterol,saturatedfats,andtriglycerides.

HypertensionBloodpressureabove140/90.IncidenceThenumberofnewcasesofadisease.InsulinApancreaticproteinthatregulatesglucoselevelsinthebloodby

helpingglucosepassintocells.InsulinresistanceReducedabilityofinsulintoentercells,evenwhenblood

insulinlevelsarehigh.KidneyfailureAconditionwheneliminationofwastesfromthebodynolonger

takesplace.Kt/VAmeasureofefficiencyinhemodialysis.LeptinAhormonethatregulateshungerbyreducingappetite;leptinmayplaya

roleinType2diabetes.LymphocytesCellswithintheimmunesystemthatprotectthebodyfrom

foreignorganisms.T-lymphocytesattacktransplantedorgans,causingrejection.

MetabolitesSubstancesformedthroughaseriesofbiochemicalreactions.Forexample,proteinisbrokendowntourea.

MutationsMistakesmadeincopyinggenesthatcancauseamalfunctionin

cellularprocessesandcanleadtoadiseaselikePKD.NephronThebasicunitofthekidney,composedofaglomerulus,tubules,and

collectingducts.OsteoporosisAconditioninwhichexcessamountsofcalciumareremoved

frombones,makingthembrittleandmoreeasilyfractured.PanelReactiveAntibody(PRA)Atesttomeasuretheamountofantibodiesin

thebloodtoassessthelikelihoodofkidneyrejection.Thehigherthevalue,thegreaterthepotentialforrejection.

ParathyroidhormoneAhormonesecretedfromthetwoparathyroidglandsintheneckthatpromotesremovalofcalciuminboneintotheblood.Thisactioncanleadtoosteoporosis.

PeritonealdialysisFiltrationofthebloodwithasolutionintheabdomen.Peritonealequilibriumtest(PET)Amethodtodeterminetheadequacyof

peritonealdialysisbymeasuringthecreatinineandureainfourhourlysamples.

PeritonitisInflammationoftheliningoftheabdomen.PharmacogeneticsTheuseofgeneticinformationtodevelopnewmedications.

Specificmutationsingenesandaccompaniedalteredproteinstructurecansuggestmechanismsunderlyingadiseasethatcanbepotentialtargetsfortherapeuticintervention.

PhosphorusAnimportantsubstanceinthegenerationofenergy.Phosphorusaccumulatesinhemodialysispatientsandcancombinewithcalciuminthebloodtoformplaquesinorgans,possiblyleadingtoorganfailure.

Polycystickidneydisease(PKD)Aninheriteddiseasecharacterizedbycyststhatgrowandultimatelydestroykidneyfunction.

PolygeneticdiseasesDiseasescausedbymutationsinmultiplegenes.PotassiumAsaltthathelpsregulateheartbeatandbrainfunction.Highblood

potassiumlevelscanleadtoheartblock.Usuallyhighpotassiumcanbetreatedbyalteringthedietorprescribingmedications.

PrevalenceThetotalnumberofpeoplewithadiseaseatagiventime.ProteinsLongchainsofaminoacidsthatoperatecellsandprovidestructurefor

thebody.ReceptorsEntitiesonorwithincellsthattranslateasignalfromahormoneor

drugintoaphysiologicalresponse;receptorsarespecificforcertainchemicalstructures,likeakeyfittingalock.

ReninAsubstancereleasedfromthekidneythatactivatestheangiotensinsystem(seeAngiotensinsystem).Undernormalconditionsithelpsmaintainbloodpressureduringdehydrationorextremebloodloss.

RestlesslegssyndromeAneurologicaldisorderthatcanaffectpeopleonhemodialysis,whoexperienceanuncontrollableurgetomovetheirlegs.

SodiumAprincipalsubstance(salt)thatdetermineshowmuchfluidthebodyretains.

TransplantationOrganreplacementtherapywhereanorganisremovedfromoneindividual(adonor),eitherlivingordeceased,andplacedinarecipient.

UreaBreakdownproductofprotein.Ureaisthemainsubstanceexcretedbythekidney.

UremiaExcessamountofureaintheblood,whichcancausedeathinkidneyfailurepatientswithoutdialysisortransplantation.

UretersLongtubesthatconnectthekidneystothebladder.UrinalysisAmethodusedtodetectbloodorproteinintheurine.Urinaryreductionrate(URR)Ameasureofefficiencyofhemodialysis.VasopressinAhormonereleasedbythepituitaryglandthatactsonthekidney

toretainfluid.VitaminDAfat-solublevitaminneededtoformandmaintainstrongbones.

VitaminDcanbemadenaturallyorsuppliedinthedietorwithsupplements.ThekidneymakesthemostactiveformofvitaminD,andwhenkidneysfail,bonestructurecandegrade,requiringtreatmentwiththemostactiveform.Thisproblemismostcommoninhemodialysispatients.

XenotransplantationTransplantationofanorganfromonespeciestoanother.

RESOURCES

Thisresourcelistisforreadersinterestedinlearningmoreaboutkidneydiseases,howthekidneyfunctions,thediagnosisandmanagementofkidneydiseases,theprinciplesofdialysisandkidneytransplantation,andothertopicsnotcoveredindetailinthisbook.Readerswhowishtogetinvolvedinacommunityofpatientsandhealthcareproviderscanusethelisttoidentifyandcontactorganizationswhosesolepurposeistoprovidesupporttopatients.Someoftheseorganizationsareadvocatesforpatientsandincludecongressionallobbyingaspartoftheiractivitiesonbehalfofpatients.

ThelistofresourcesandorganizationsisnotexhaustivebutdoesincludesourcesthatIfoundmostinformativeandauthoritative.

EDUCATIONALRESOURCESTheInternetisaseeminglyunlimitedsourceofinformation.Websitesprovideinformationandsupport,andscientificdatabaseslinktoprimaryresearcharticlesonkidneydiseases.TheNationalLibraryofMedicineattheNationalInstitutesofHealthprovidesthebestdatabases;seewww.nlm.nih.gov.ThemostusefuldatabasesarePubMedandtheNLMGateway.PubMediseasiertouseforsimplesearches;beginyoursearchesatwww.ncbi.nlm.nih.gov/PubMed.

ThewebsiteoftheNationalInstituteofDiabetes,Digestive,andKidneyDiseasesincludesadirectoryofKidneyandUrologicDiseasesOrganizations;seewww.kidney.niddk.nih.gov/resources/organizations.htm.Severaloftheseorganizationsexistforthesolepurposeofsupportingpatientswithspecificdiseases.Herearesomeofthem.

AmericanDiabetesAssociationAttn:NationalCallCenter1701NorthBeauregardStreetAlexandria,VA22311Phone:1-800-DIABETES(1-800-342-2383)Website:www.diabetes.org

Accordingtotheirwebsite,themainmissionoftheAmericanDiabetesAssociationis“topreventandcurediabetesandtoimprovethelivesofallpeopleaffectedbydiabetes.”Thesitehasextensiveinformationforpatientsandprofessionalsaboutdiabetes,managementofthedisease,preventative

andprofessionalsaboutdiabetes,managementofthedisease,preventativemeasures,weightloss,andstatistics.TheAmericanDiabetesAssociationalsoprovidesgrantstohelpsupportthesalariesofyounginvestigatorsdoingresearchondiabetes.

AmericanHeartAssociationNationalCenter7272GreenvilleAvenueDallas,TX75231Phone:1-800-242-8721Email:ThroughthewebsiteWebsite:www.americanheart.org

ThewebsiteoftheAmericanHeartAssociationprovidesinformationonmanyaspectsofcardiovasculardisease,includinghypertension.OnedivisionoftheAmericanHeartAssociationistheAmericanStrokeAssociation,whichprovidesinformationonwarningsigns,prevention,andcareforstrokepatients.

AmericanStrokeAssociationNationalCenter7272GreenvilleAvenueDallas,TX75231Phone:1-888-478-7653Email:ThroughthewebsiteWebsite:www.strokeassociation.org

Noorganizationisdevotedspecificallytoglomerulonephritis.Thewebsitewww.mayoclinic.comprovidesgoodinformationonthedisease.Inaddition,twoorganizationsexistspecificallytoaddresstwocausesofglomerulonephritis:theAlportSyndromeFoundationandIgANephropathySupportNetwork.

AlportSyndromeFoundation1608E.BriarwoodTerracePhoenix,AZ85048-9414Phone:480-460-0621

Website:www.alportsyndrome.org

Alportsyndromeisagenetickidneydisease.ThemissionoftheAl-portSyndromeFoundationis“toeducateandsupportpatientsandfamiliesthathavebeenaffectedbyAlportSyndromewiththegoaloffundingresearchtofindmoreeffectivetreatmentprotocolsandacure.”

IgANephropathySupportNetwork89AshfieldRoadShelburneFalls,MA01370Phone:413-625-9339Website:www.igansupport.org/index.html

ThemissionoftheIgANephropathySupportNetworkis“toassistpatientswithIgAnephropathyandtheirfamilies;toserveasaclearinghousefordisseminationofinformationaboutIgAnephropathy;andtopromoteresearchforapossiblecure.”Thenetworkprovidesnewslettersandpamphlets.

PKDFoundation8330WardParkway,Suite510KansasCity,MO64114-2000Phone:1-800-PKDCUREEmail:pkdcure@pkdcure.orgWebsite:www.pkdcure.org

Thebestplacetoobtainusefulandreliableinformationonpolycystickidneydisease(PKD)isthroughthePKDFoundation,whichprovideseducationalmaterialforpeoplewithPKD,theirfamilies,andotherinterestedparties.Inaddition,itfundsgrantstoresearcherswhoareworkingtoidentifythecausesofPKDaswellaspotentialtreatmentsandcuresforthisinheritedkidneydisease.ThePKDFoundationistheonlyorganizationintheworldthataddressesPKDexclusively.IdidnotdiscussARPKDinthisbookbecausemostpatientshaveADPKD.ForreadersinterestedinARPKD,aplacetostartlearningmoreisfoundatthelinkonthePKDFoundationwebsite.

NationalKidneyFoundation30East33rdSt.,Suite1100NewYork,NY10016Phone:1-800-622-9010Email:info@kidney.orgWebsite:www.kidney.org

TheNationalKidneyFoundationisanorganizationthatprovidesexceptionallyvaluableinformationonkidneydiseasesingeneral,aswellasondialysisandtransplantation.TheNKFoffersnumerouspamphletsdescribingmanydifferentaspectsofkidneyfailure.Thisisausefulsiteforlearningbasicinformationaboutkidneyfailure.

AmericanAssociationofKidneyPatients3505E.FrontageRd.,Suite315Tampa,FL33607Phone:1-800-749-2257Email:info@aakp.orgWebsite:www.aakp.org

TheAmericanAssociationofKidneyPatientshasasitethatisdevotedtopatientissues.Accordingtotheirwebsite,theorganization“existstoservetheneeds,interests,andwelfareofallkidneypatientsandtheirfamilies.Itsmissionistoimprovethelivesoffellowkidneypatientsandtheirfamiliesbyhelpingthemtodealwiththephysical,emotional,andsocialimpactofkidneydisease.”Thewebsitehasextensiveinformationonallaspectsofkidneydisease.

NUTRITIONAswelearnedinchapter5,itcanbedifficultforapersonwithkidneydiseasetoeataproperdietandmaintaingoodnutrition,becauseofalimitedlistofpermittedfoods.Thisisespeciallytrueforanyoneonhemodialysis.TheAmericanAssociationofKidneyPatientspublishesausefulbrochurethatliststhesodium,potassium,protein,andcaloriccontentofawidevarietyoffoods.Thisbrochurecanhelpyouinselectingmealsthatmeettherequirementsofhemodialysis.Youcandownloaditfromwww.aakp.org/brochures/nutrition-counter.

Peopleondialysis,especiallyperitonealdialysis,generallymusthaveproteinsupplementation.Liquidsupplementsdesignedfordialysispatientsareavailable,buttheyareexpensive.Forme,abetteralternativewasaproteinpowderderivedfromeggwhites.Youcanpurchasepowderedeggwhitesatwww.optimumnutrition.comoratalocalGNC.Thelattersourceisoftencheaper.Note:donotbuywheyprotein.Derivedfromdairyproducts,theproducthasahighphosphoruscontent.

ThePKDFoundationrecentlypublishedacookbookentitledBrilliantEats:SimpleandDeliciousRecipesforAnyoneWhoWantstobeKidneyWise.Thiscookbookissuitableforanyonesufferingfromchronickidneydiseasefromanyofthemajorcauses.Itidentifiesrecipessuitableforpeopleinpre-dialysis,hemodialysis,andperitonealdialysis,andforpeoplewhoareconsideringorpreparingfortransplant.Thebookcanbepurchasedatwww.kidneywise.org.

TRANSPLANTDONORWEBSITESBecausethereisashortageofkidneysavailablefortransplantation,effortsareunderwaytoidentifymorelivingdonors.Severalorganizationshavebecomeincreasinglyactiveinmatchinglivingdonors.

AllianceforPairedDonation3661BriarfieldBoulevard,Suite105Maumee,OH43537Phone:419-866-5505Email:admin@paireddonation.orgWebsite:www.paireddonation.org

Throughanationwidecomputer-matchingprogram,theAllianceforPairedDonationhelpsarrangeforlivingdonationsbetweenpairsofpotentialdonorsnotcompatiblewiththepatientswithwhomtheyoriginallyintendedtodonate(seechapter7).Theorganizationhasbeeninexistenceforonlyafewyears,butasofthiswriting,ithasarrangedseventeenpaireddonations.Althoughitdoesnothaveagreementswithhospitalsinallfiftystates,itisworkingtoaccomplishfullcoverage.Registeringiseasyandfree.

NationalKidneyRegistryPOBox460Babylon,NY11702-0460Phone:1-800-936-1627

Email:administration@kidneyregistry.orgWebsite:www.kidneyregistry.org

TheNationalKidneyRegistrywasfounded“tosaveandimprovethelivesofpeoplefacingkidneyfailurebyincreasingthequality,speed,andnumberoflivingdonortransplantsintheworld.”Althoughtheorganizationonlybeganitseffortsin2007,ithasambitiousplansoverthenextfiveyears.Itwantstoprovideupto10,000livingdonationsperyearforthoseneedingakidneytransplant.Thecostisfreefordonorsandrecipientswhoworkthroughoneoftheparticipatingcenters.SinceFebruary2008,NKRhasfacilitatedeighty-eighttransplants,accordingtoitswebsite.

MatchingDonors.com,Inc.766TurnpikeStreetCanton,MA02021Phone:781-821-2204Email:contactus@matchingdonors.comWebsite:www.matchingdonors.com

Accordingtoitswebsite,theorganizationwas“createdtogivepeopleinneedoftransplantsurgeryanactivewaytosearchforaliveorgandonor.Ourgoalistoincreasethenumberoftransplantsurgeriesandimproveawarenessofliveorgandonation.”Asthenameimplies,MatchingDonors.com,Inc.,attemptstomatchprospectivelivingdonorswiththoseinneedofatransplant.AsofJanuary2010,1,495peoplewhoarewillingtodonatekidneyshavebeenlisted,and240peoplehaveregisteredinneedofone.Morethan100transplantshavebeencompleted.

Beinglistedasapatientonthesiteinvolvespayingafee.Theamountdependsonthelengthofthelisting.Itrangesfrom$295foramonthlymembershipto$595foralifetimemembership.Currently,Medicareandinsurancecompaniesdonotreimbursethisexpense.Forthosewhocannotaffordthefee,MatchingDonorsclaimsthatitwaivesit.

Ifyoupursuelivingdonationsthroughanyofthesewebsites,youmustdosoincloseconsultationwithyourtransplantsurgeon.Itisnotclearfromthesiteswhetherthoseinvolvedintheorganizationadequatelyscreenpotentialdonorsforpossiblemedicalconflictsorotherdisqualifyingfactors.

FINANCIALAID

FINANCIALAIDThecostsfordialysisandkidneytransplantationaresubstantial.Althoughsomeprivateinsuranceprovidescoverage,notallinsurancedoes,andmanypatientshavenoprivateinsurance.AmajorsourceoffundingfordialysisandtransplantationcomesfromthefederalgovernmentthroughMedicareandMedicaid.Medicarecanprovidesignificantassistancetothoseinneedwhomeeteligibilityrequirements.Usefulinformationcanbefoundinthebrochure“MedicareCoverageofKidneyDialysisandKidneyTransplantServices”availableattheMedicarewebsiteatwww.medicare.gov/Publications/Pubs/pdf/10128.pdf.Forfurtherinformation,youcancallMedicareat1-800-MEDICARE(1-800-486-4028).ForMedicaid,ajointfederalandstateprogram,benefitsvarydependingonthestateandeligibilityrequirements.Checkwithyourstateagencyforfurtherinformation.

TheAmericanKidneyFundprovidesfundstodefrayexpensesassociatedwithdialysisandtransplantationthatinsurancedoesnotcover.TheFundalsoprovidesbrochuresaboutkidneyfunctionandkidneydiseasesandeducationalseminars.

AmericanKidneyFund6110ExecutiveBlvd.,Suite1010Rockville,MD20852Phone:1-800-638-8299Email:www.kidneyfund.org/about-us/national-headquartersHomepage:www.kidneyfund.org

Otherorganizationsexistthatprovidehelpfortransplantcosts,includingthecostoftravelingtothetransplantcenter.Awebsitewithalistofsomeoftheseorganizationsandlinkstothemcanbefoundatwww.classkids.org/library/resourc/fundraising.htm.

Finally,countyservicesprovidedbylocalgovernmentsorprivateorganizationsalsoassistincoveringsuchcostsofdialysisastransportation,aswellastransplantationcosts.Checkwiththesocialworkeratyourdialysisortransplantcenterforguidance.

INDEX

acceptance,5–6,66,160acidity,21acidosis,21,60,63,163acyclovir,139adrenalglands,21,163advocacybypatients,10–11,160albumin,104albuminuria,33–34,163aldosterone,21,163alpha-blockers,75AllianceforPairedDonation,175AlportSyndrome,39AlportSyndromeFoundation,173AmericanAssociationofKidneyPatients,111,174–75AmericanDiabetesAssociation,172AmericanHeartAssociation,172AmericanKidneyFund,177AmericanStrokeAssociation,172AmericanswithDisabilitiesAct,106amputations,31anemia,59,62–63,104,163aneurysms,46,163anger,5–6angiotensinI,20angiotensinII,21,74angiotensinIIreceptorantagonists,74angiotensinconvertingenzyme(ACE),74,163

angiotensinsystem,67,78andregulationofbloodpressure,20–21,37–38

angiotensinogen,20antibiotics,80,137–39antibodies,39–40,76,133antifungalagents,137–39antigens,119–20,164anti-thymocyteglobulin,138,146antiviralagents,137–39Aransep,59artificialinterferon,151atenolol,75AthenaDiagnostics,46atherosclerosis,37,163atorvastatin,139autosomaldominantpolycystickidneydisease(ADPKD),41–43,163,174autosomalrecessivepolycystickidneydisease(ARPKD),41–43,163,174

Bactrim,139bargaining,5–6basilixamab,138BaxterInternational,Inc.,91,162beta-blockers,75betacells,29,77Betadyne,86,94bicarbonate,21birthdefects,31blindness,31bleeding,102bloodpressure,regulationof,21,35–37,67bloodtyping,123,128–29,164

bloodureanitrogen(BUN),51,104,140–41,164biopsy,57,164bone:demineralization,20,140regulatingstructureof,22

bonemarrow,22,164brain,33,75Bright,Richard,27

calcidiol,23,164calcitriol,23,61,164calcium,50,164roleinbonehealth,22,104roleintransplantcomplications,140fortreatingboneloss,6

calciumacetate,61calciumcarbonate,61calcium-channelblockers,75cancer,72,78,139,152,155CAPD.Seecontinuousambulatoryperitonealdialysiscarbohydrates,17,164carbondioxide,17,164carbonicacid,21cardiovasculardisease,31,140,155catheter,164usedinhemodialysis,99–100usedinperitonealdialysis,84–87,94,109

CCPD.SeecontinuouscyclicperitonealdialysisCellcept,138CentersforDiseaseControlandPrevention,U.S.,31cholecalciferol,23,165cholesterol,23,72–73,139

chromosomes,25,150,165clinicaltrials,75–79,141–48clinicaltrials.gov,75,141clonazepam,116clotrimazoltroche,139clotting,102collectingduct,18computerizedtomography(CT),indiagnosis,44–45continuousambulatoryperitonealdialysis(CAPD),87–91,165continuouscyclicperitonealdialysis(CCPD),91–94,165travelingand,106

copingskill(s),10–15askingforhelp,14–15,160believinginrecovery,12,160embracinginnerstrength,11feelingincontrol,8–9,160humoras,15,160movingpastdenial,10,160andoptimism,13andpriorities,13,159–60andrisk-taking,13–14,160andself-advocacy,10,160

Cozaar,74creatinine,51–52,165andkidneyfunction,55levelsaftertransplantation,140,147levelversusstability,57andperitonealdialysis,94

creatinineclearance,51–52,95,165crossmatch,133,165cyclosporine,138

cysts,40–41,44–46,78cytomegalovirus,139

daclizumub,138dailyhemodialysis,97,162Darbepoetin,59deceaseddonors,129–34bloodtyping,132kidneyallocation,130–33

Deltazone,138denial,5–6,66,160deoxyribonucleicacid(DNA),25,165depression,5–6diabetes,2,24,27–34,49,67complicationsof,31andgeneticfactors,31–32,161prevalenceof,3,27–28,30–31preventionof,65roleofobesityin,32–34,67andtransplantcomplication,139,155treatmentof,76–77Type1,29–30,76–77Type2,30–34,76–77

diabeticnephropathy,34,161,165dialysate,xii,84,91,94,165dialysis,80–117,165basicprinciplesof,81–83consentformfor,9costsof,177anddiets,110andfuturetreatmentoptions,153–55

andgeneticvariation,31–32,152andhealthmonitoring,103–5historyof,80–81,83incidenceof,3–4prevalenceof,3,27,81

dialyzer,96–97,154–55,165diet,30,175anddialysis,110–14tomaintainkidneyfunction,58–59,67–68

dietitian,70,111,113diagnosis,49–64diastolicbloodpressure,35–37diuretics,58,75donors:deceased,129–34expandedcriteria,132–33GoodSamaritan,126living,124–29poolof,125–26standardcriteria,132–33

drugmetabolism,151

edema,58,140,165education,171–74aboutkidneydisease,7–9,66,159abouttreatmentoptions,50

electrolytes,16,166emotionalreactions,4–7,9,10end-stagerenaldisease(ESRD),48,161environmentalfactorsin,26geneticfactorsin,24–26andMedicarespending,4

prevalenceof,2roleofobesityin,67

environmentalfactorsinkidneydisease,26,30enzymes,150–51Epogen,59Epstein-Barrvirus,139,147erythrocytes,16,22,104,166erythropoietin(EPO),166roleinerythrocyteproduction,22fortreatinganemia,59,62–63,104

ESRD.Seeend-stagerenaldiseaseexchange,166exercise,67–68,140exitsite,84,107expandedcriteriadonors,132–33experimentalmedications,75–79

fat,72–73fatdeposits,67,72fear,5–6fenofibrate,139,147financialaid,177–78fishoil,147fistula,100–101,166fluidretention.Seeedemafreefattyacids,33FoodandDrugAdministration(FDA),143–44foodlabels,71–73Fresenius,162furosemide,60

GeneralNutritionCenter(GNC),106,175

genes,24,78,166roleinmakingproteins,25

genesequencing,152–53GeneticInformationNon-discriminationActof2008,47,153genetictests,46–48forPKD,46andproblemsassociatedwithinsurability,47

genetics:roleinhypertension,37roleinkidneyfailure,24–26roleinPKD,43–44roleinType1diabetes,30roleinType2diabetes,31–32

Gengraf,138glomerulardiseases,24,27,38–40incidenceof,3–4prevalenceof,2treatmentof,77–78

glomerularfiltrationrate(GFR),50,166andassessingkidneyfailure,52–55,57,63guideforplacingdialysiscatheters,98monitoringtransplantfunction,141

glomerulus,18,38–40,77,166glucose,28,50,76,84,95,166GoodSamaritandonors,126Gore-Tex,100graft,100–101,166

half-lifeofkidneytransplants,123–24HealthyChoice,70,139heartdisease,67,72hematocrit,55,166

hematuria,50hemodialysis,79,81,83,96–105,166daily,97,153,162dietswith,110–15efficiencyof,102–3andfuturetreatmentoptions,153–55home,97nightlyhome,154,162andphosphorusrestriction,111,113andpotassiumrestriction,111–13prosandconsof,108–17,153andsodiumrestriction,110–11andwearablemachines,154,162

hemoglobin,50,55,166heparin,102,166hepatitis,121,151herpes,139HIVandtransplants,121,129HLAtyping,120,166homehemodialysis,97homeostasis,17,166hormones,32,160HumanGenomeProject,25,150hydrochlorothiazide,75hyperlipidemia,50,139,167hypertension,24,27,35–38,48–50,167geneticfactorsin,37,161incidenceof,3–4prevalenceof,2,35preventionof,65roleof,inotherdiseases,67

roleof,intransplantation,140treatmentof,50,73–75

Hytrin,75

immunesystem:roleinglomerulardisease,39–40roleintransplantation,119–20roleinType1diabetes,29–30,76–77

immunoglobulinA(IgA)nephropathy,39immunoglobulins,39immunosuppressants,78,137–40,142–43,147,155immunosuppression,77–78,156–57incidenceofESRD,2,167infections,99–100,106–7,110,137–39,142,153inflammation,33,38–39,77IgANephropathySupportNetwork,173innerstrength,11–12insulin,28,29,76–77,167roleinglucosemetabolism,28–30

insulinresistance,32–33,76,167insurance,128,154,177iron,104inrestlesslegssyndrome,115

islettransplants,77

Kayexalate,60kidneybiopsy,40,57kidneydisease,stagesof,53–55kidneydonors,122–34KidneyEarlyEvaluationProgram,49–50kidneyfailure,167.Seeend-stagerenaldisease(ESRD)kidneyfunction:evolutionof,17filtration,17–20

phosphorousrestrictioninmaintaining,70proteinrestrictioninmaintaining,70saltrestrictioninmaintaining,69–70

Klonopin,116KT/V,102–3,167Kübler-Ross,Elisabeth,5,161

Lasix,60LeanCuisine,70leptin,32–33,167Lipitor,139lisinopril,74liverfunction,104livingdonors,124–29evaluationof,127andGoodSamaritandonors,126andmedicalcosts,127–28numberandpercentageof,124–25andsurgery,127.Seealsodonors

Loniten,75losartan,74lupuserythematosus,39,77lymphocytes,119–20,167lymphoma,139

macroalbuminuria,33,163magneticresonanceimaging(MRI),45,56managingkidneyfailure,58–61MatchingDonors.com,125,176MayoClinic,173Medicaid,177medicaltourismandtransplants,126

Medicare,4,127–28,145,154,177Medications:developmentof,150–53experimental,75–79

Medrol,138metabolismofcarbohydrates,17metabolites,16,167methylprednisone,138microalbuminuria,34,163Microzide,75minerals,73minoxidil,75Mirapex,116monounsaturatedfats,72morphine,146mutations,25–26,167indiabetes,31–32inPKD,41–44,78

Mycelex,139mycophenolatemofetil,138mycophenolicacid,138Myfortic,138

NationalInstituteofDiabetes,Digestive,andKidneyDiseases,171NationalInstitutesofHealth,8,30,35,66,80,141–42,171NationalKidneyFoundation,49,174NationalKidneyRegistry,125,176NationalLibraryofMedicine,8,171nauseaandvomiting,62–63Neoral,138nephrologist,55–58,70nephron,18,167

nervedamage,31NewEnglandProgramforKidneyExchange,125nightlyhomehemodialysis,154,162NLMGateway,171

obesity,73,161roleindiabetes,4,30,67roleindisease,26roleinhypertension,38,67roleinkidneyfailure,4andtransplants,121

ondansetron,62optimism,13OptimumNutrition,105,175osteoporosis,22,140,155,167pairedkidneydonation,126–27pancreas,30pancreaticisletcells,77panelreactiveantibody(PRA),133,167parathyroidhormone,50,61,104,168paricalcitol,61PatientProtectionandAffordableCareActof2010,47,153peritonealdialysis,81,83–96,105–8,168efficiencyof,94exchanges,87–94percentageofpeopleusing,105withpolycystickidneydisease,107principlesof,83–87prosandconsof,105–8,153andproteinloss,105sideeffectsof,106–7,153

peritonealequilibriumtest(PET),95,168peritonealmembrane,83–84peritonitis,95–96,107,153,168pharmacogenetics,151–52,168PhosLo,61phosphorus,17,50,60,73,104,168eliminating,22monitoring,109andphosphateplaques,22restrictionof,70–71,111roleinbonehealth,22treatinghighlevelsof,60

pirfenidone,77pituitarygland,78PKDFoundation,40,162,173,175polycystickidneydisease(PKD),xi,2–3,24,27,40–46,49,149,168diagnosisof,44–45,162andepithelialcells,44andgenes,44healthconsequencesof,45–46incidenceof,3–4andlivingdonorproblems,126andmutations,27,41–44prevalenceof,3,40peritonealdialysisin,107treatmentof,78–79

polycystin-1,44polycystin-2,44polygeneticdiseases,31,168polyunsaturatedfats,72potassium,60,73,104,168

monitoring,107restriction,111

pramipexole,116Pravachol,147pravastatin,147prednisone,138prevalence:ofdiabetes,27–31ofglomerulardiseases,38ofhypertension,35ofkidneydisease,xi,2,168ofpolycystickidneydisease,40

Prinivil,74Prograf,138proteins,25,104,168restricting,70supplementing,105,175

proteinuria,50PubMed,171

Rapamune,138Rapamycin,138receptors,32,168recovery,12Reeve,Christopher,12renin,20,168Requip,116restlesslegssyndrome,114–16,168retroviruses,156Rocaltrol,61ropinirole,116

scarring,38–40,77–78

sensitizationintransplantation,133signsandsymptomsofkidneyfailure,61–64Similect,138simvastatin,139sirolimus,78,138,147smoking,50socialworker,109sodium,72–73,169exchangewithbicarbonatetobalanceacidity,21andfluidretention,110–11restriction,69–70roleinhypertension,37–38

sodiumbicarbonate,60sodiumcitrate,60sodiumpolystyrenesulfonate,60stemcells,156–57,162steroids,138,155strokes,31,172sulfamethoxazole/trimethoprim,139systolicbloodpressure,35–37

tacrolimus,138,147–48Tenormin,75terazosin,75thrombinplasminogenactivator,110Thymoglobulin,138,146T-lymphocytes,119,146,156tolvaptan,78transplantation,xiii,78,118–48,169antigenmatching,119–20candidacyfor,120–22

candidatesreceivingtransplants,112–23costsof,177crossmatchfor,133anddonors,122–34anddonorwebsites,175–77inelderlypeople,133andevaluation,127–29futureapproachesto,155–57historyof,118–19andkidneysurvival,123–24andmedicaltourism,126andpairedkidneydonation,126–27andpost-transplantcare,137–41andrejection,118–20,133,137–38,141–43,155andsensitization,133surgery,127,135–37andsurvival,123–24waitingfor,134–35,162

Tricor,139,147triglycerides,50,139tubules,18Tums,61tunneled,cuffedcatheter,99–100Type1diabetes.SeediabetesType2diabetes.Seediabetes

ultrasound,indiagnosisofPKD,44–45UnitedNetworkofOrganSharing,122,124allocationsystemfortransplants,130–32,134

untunneledcatheter,99urea,20,51,95,103–4,169

uremia,80,169ureters,136,169urinalysis,50,169urinaryreductionrate(URR),102–3,169urine,productionof,19–20

Valcyte,139valganciclovir,139vascularaccessesforhemodialysis,98–102blockageof,110

vasopressin,78,169vasopressininhibitor,78vitaminD,17,22–23,169synthesisof,23treatinglowlevelsof,61

vitamins,73inrestlesslegssyndrome,115

waitinglistsfortransplants,130–32,135–36waterpills,75wearablehemodialysismachines,154weightgain,107,140weightloss,50,67–68

xenotransplantation,156,169

Zemplar,61Zenapax,138Zestril,74Zocor,139Zofran,62Zovirax,139

AbouttheAuthor

WalterA.Hunt,Ph.D.,holdsabachelor’sdegreeinchemistryfromBethanyCollegeandadoctorateinneuropharmacologyfromWestVirginiaUniversity.Asamedicalresearcherforthirtyyears,heexaminedthebiologicalbasisofdiseasesneverconsideringthatonedayhewouldhavetodealwithaseriousdiseaseofhisown.Havingpolycystickidneydisease(PKD),thefourthleadingcauseofkidneyfailure,hesufferedsevenandahalfyearsofdialysisandtwodozenstaysinthehospitalbeforereceivingthegiftoflifeofatransplant.Nowfreeofkidneyproblems,Dr.HuntservesontheBoardofTrusteesofthePKDFoundationandtravelstheworld.