&

DR.A.NILAVAN PG II YEAR

Anatomic changes

PHYSIOLOGICAL CHANGESSYSTEMIC HEMOYNAMIC CHANGES # plasma volume increase by 50 to 60% # c.o increase by 40to 50% # hypo tension ( 10 mm hg decrease)

RENAL HEMODYNAMICSGLOMERULAR CHANGES # RPF increases by 60% # GFR increases by 50% # sr creatinine decreases inspite of these changesIntraglomerular blood pr isunchanged and this has long term effect on renal function

TUBULAR CHANGES

Cont….Pre-pregnancy Pregnancy

Uric acid(mg/dl) 4 3.2 (early) 4.3 (late)

Sodium(mmol/l) 140 135

Pottasium(mmol/l) Slight increase

BUN(mg/dl) 12.7 9.3

Urea(mmol/l) 4.5 3.3

Vitamin/ amino acid decreasesProtein(g/dl) 7 6(proteinuria)

glucose glucosuria

ca decreases

Osmolality(mosm/kg) 285 275

Common changes in pregnancyPre-pregnancy pregnancy

Hematocrit% 41 33

Plasma protein(g/dl) 7 6

Plasma osmolality(mosm/kg)

285 275

Plasma sodium(mmol/l)

140 135

Plasma creatinine(mg/dl)

0.8 0.5

BUN(mg/dl) 12.7 9.3

Plasma urea(mmol/l) 4.5 3.3 pH 7.40 7.44

PCO2(mmhg) 40 30

Hco3(mmol) 25 20

SBP(mmhg) 115 105

DBP(mmhg) 70 60

Renal complications in pregnancyUTI & Asymptomatic bacteriuriaHypertensive disorders of pregnancyAcute renal failureRenal calculiAbnormal urinalysis

Urinary Tract Infection1-2 % of pregnancyAssosiated with SGA , IUD, premature labour,

Hypertension and anemiaPersistant leukocyturia (2-3 wbc/HPF)

Significant bacteriuria105

102 with symptoms cystitis/ pyelonephritis

Cont…Pyelonephritis

70% have asymptomatic bacteriuriaMostly in second trimesterSymptoms – Pain, fever, dysuriaComplication – Endotoxic Shock, DIC, ARFTreatment

Hydration IV Antibiotics for 24 – 48 hours Change to oral antibiotics for 10-14 days

Cont…Cystitis

Symptoms – Urgency, frequency and dysuria without systemic signs

Culture may be negativeRecurrence is 17%Usually doesnot progress to pyelonephritis

Asymptomatic Bacteriuria2-7% Without pyuria30% will progress to pyelonephritisIncreases risk of premature labour and low

birhtweight urine culture

Repeat culture in high risk patient( repeated UTI and anomalies)Treatment : Cephalosporins for 3-7 days(pyelonephritis risk reduced to 3%)Recheck culture after 2-3 weeks ( recurrence 35%)

2 or more repeated infection

Supressive therapy with nitrafurantoin and cephalosporins

Safety of antibioticscategory Antibiotic

A.

Drugs taken by large no of pregnant women with out any proven harm

Amox, ampi,cefalexin,Cephalothin,nitrofurantoin,penicillin

B1 Taken by limited no of pregnant women with out proven harm; animal studies show no increase in fetal harm

Aztreonam, ceftazidime,cefataxime, cefaclor, amox/clavulanic acid,piperacillin

B2 As B1, but animal data unavailable

Vancomycin

B3 As B1,but animal studies show an increase in fetal damage

Cipro, norfloxacin, ofloxacin,imipenem,Trimethoprim

C Drugs whose pharmalogic effects are suspected of causing harm

Sulphonamides,Cotrimoxazole,fusidic acid

D Proven to cause fetal harm

Tetracycline, gentamycin,Chloramphenicol

HYPERTENSION

PRE ECLAMPSIA

New onset hypertension(140/90mmhg) & proteinuria after 20 weeks( PC ratio 0.3 μg/ mg creatinine)

EdemaUric acid >5.5mg/dl

PATHOGENESIS wide spread endothelial dysfunction and micro angio pathy in mother

Severe preeclampsiaBP 160/110

Urine PC ratio >5μg/mg or proteinuria >5g/24 h urine

Oliguria

CVA , seizures, visual disturbance

Pulmonary edema

Epigastric or rt upper quadrant pain

Hepato cellular injury

Sr LDH >600 iu/l

Thrombocytopenia < 100000(HELLP syndrome)

IUGR

Natural HistoryProteinuria and hypertension usually will disappear

within days or weeks, sometimes may take maximum of six months

Renal Biopsy – Proteinuria for more than six months, Deteriorating renal function,

Presence of Urinary Sediments

Predicts future hypertension 7-37% and future cardiovascular risk

Prevention75-80 mg AspirinCalciumVit C and E do not protect

Management Bed restWeight loss & salt restriction not recommendedAnti hyper tensive

ACE inhibitors& ARB contraindicated.

Diuretics should be used carefully .

Alfa methyl dopa is the drug of choice.

Hydralazine is drug of choice in emergencies.

β blockers can be used.

CCB may cause tocolysis in third trimester

Management of preeclampsiaPROBLEM MANAGEMENT

Control blood pr Acute Rx if BP >170/110Chronic Rx if BP>140/90

Eclampsia Diazepam 10-20mg to terminate convulsionMagnesium sulfate for neurological sign 4 g IV over 20 minutes then 1.5 g/hr for 48 hrs

Volume expander therapy 500-1000 ml of colloid over 4-6 hr for persistent oliguria

Supportive therapy Platelet infusion if count <20000-40000FFP for micro angiopathyDialysis for ARF

Progressive decline in renal, hepatic or clotting function or fetal growth

Delivery

Type of hyper tension

drug Rx given

Acute Hydralazine 5 mg bolus every20- 30 min (max 20 mg) then infusion at 5-10 mg/hr

Labetolol 50 mg 20 every min (max 300mg)

Nifidipine 20 mg oral

Chronic

first line Methyl dopa 500-2000mg/day PO

Clonidine 0.2-0.8 mg /day PO

Labetolol 200-1200mg/day PO

Atenolol 50- 100 mg/day PO

Second line Hydralazine 25-200 mg/day PO

Prazosin 1-10 mg/day PO

Nifidipine sr 40-100 mg/day PO

Acute renal failure in pregnancyRenal failure in early pregnancy

Prerenal azotemiaCauses

Hyperemesis gravidarum Hemorrhage associated with spontaneous abortion

Acute tubular necrosisCauses

Severe volume depletion (hyperemesis gravidarum, hemorrhage from spontaneous abortion, or shock secondary to septic abortion )

Cont….Renal Cortical Necrosis

Cause The disorder is most likely initiated by primary disseminated

intravascular coagulation in the setting of severe renal ischemia

It is more commonly associated with pregnancy. C/F- gross hematuria, flank pain, and severe

oliguria/anuria following an obstetric catastrophe (abruptio placentae, septic abortion, retained fetus, amniotic fluid embolism).

The diagnosis can usually be confirmed by demonstrating a radiolucent rim in the cortex, using computed tomography (CT) scanning.

Recovery typically requires months, and renal functional recovery is usually incomplete.

Cont….PyelonephritisThrombotic thrombocytopenic purpura(TTP)

While TTPand hemolytic uremicsyndrome represent a spectrum that includes microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, TTP is more likely to occur in the first trimester and generally does not cause severe renal failure.

Patients may have a severe deficiency of ADAMTS-13.

Plasma exchange is the primary treatment

Renal failure in late pregnancyCauses1.Preeclampsia and the associated disorders

(eclampsia and HELLP)2.Acute tubular necrosis

causes- Preeclampsia, HELLP syndrome Uterine hemorrhage with abruptio

3.Acute fatty liver of pregnancy

Cont…Acute fatty liver of pregnancy

c/f- abdominal pain and jaundice, typically occurring after week 34 of gestation.

Bilirubin is elevated, with mild elevations of aspartate aminotransferase and alanine aminotransferase levels also occurring. Severe cases can present with fulminant hepatic failure.

The disorder is commonly associated with acute renal failure.

Noninvasive imaging can also provide evidence of fatty liver.

Pathogenesis- microvesicular fatty infiltration of hepatocytes, which may related to defective mitochondrial beta-oxidation of fatty acid

Rx- Immediate delivery and supportive care. Most patients fully recover

Postpartum renal failureHemolytic uremic syndrome

severe hypertension, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.

Postpartum acute renal failure usually presents days to weeks following a normal delivery and may be related to retained placental fragments

Hemolytic uremic syndrome can be difficult to differentiate from severe preeclampsia or HELLP syndrome and may require renal biopsy for diagnosis(presence of schistocytes may be help ful)

Other causes of acute renal failure in pregnancyObstructive Uropathy

moderate or severe dilatation of the collecting system in women with oliguria or anuria

Etiologies of obstructive uropathy include gravid uterus, polyhydramnios, kidney stones, and enlarged uterine fibroids.

Obstructive uropathy usually resolves with delivery, although ureteral stenting may be required preterm.

Nephrolithiasis

Antiphospholipid syndrome All pregnant women with lupus should be screened for

antiphospholipid antibodies and lupus anticoagulant. These women are at increased risk for fetal loss and worsening

of renal function. Treatment with low-dose aspirin or heparin depends on

antibody levels and previous obstetric history of early fetal loss and/or thrombo

Management ARFRestoration of fluid nvolumeAppropriate antibioticsDelivery of baby as early as possibleDIALYSIS – individualised - sr. creatinine ≥3.5 mg/dl

URINALYSISHematuriaProteinuriaPyuria

Hematuria Microscopic

Hematuria20 % of normal

pregnancyLupus NephritisIg A NephropathyTMDCalculiPolycystic Kidney

DiseaseSickle cell trait

Macroscopic HematuriaHemorrhagic

bacterial cystitisNeoplasmCalculi

ProteinuriaMore than 300mg/day or Urine PC ratio 0.3

mg per milligram of creatinineDD

Renal CalculiPreeclampsiaNew Onset glomerular disease

PyuriaMay be due to infection or contamination of

Vagina

NephrolithiasisDecrease risk of calcium stoneThough calciuria/ dilatation/ stasis, there is increased

excretion of inhibitor of stone formation( magnesium, citrate, nephrocalcin)

Decreased risk of uric acid &cystine stone due to gestational bicarbonateamia and alkalanisation of urine Xanthine oxidase and d-pencillamine avoided especially during Ist

trimester

Complication preterm rupture of membranes UTI-Management : treatment for longer period followed by antibiotic

prophylaxis • Ultrasonography is the primary diagnostic imaging modality. • Ureteral stenting may be necessary if the stones cannot be

passed.

PREGNANCY WITH PRE-EXISTING KIDNEY DISEASE

Effects on Renal disease

Effects on Pregnancy outcome

RENAL FUNCTION:

Mild: Serum creatinine < 1.4GFR >50 ml/min

Mild/ no deterioration of renal function

Preterm labour

Moderate:Serun Creatinine 1.5-1.9GFR 25-50ml/min

40% decline in renal function, but 50% will have recovery

2%----ESRD

Preterm labourPreeclampsiaIUGR

Severe:Serum Creatinine >2GFR <25ml/min

2/3----rapid decline1/3-----ESRD

Preterm labourPreeclampsiaIUGR

Cont…

Effects on Renal Disease

Effects on Pregnancy Outcome

PROTEINURIA>500mg /24hr urine

ThromboembolismRisk for chronic hypertensionPoor long term renal prognosis

Preterm labourPreeclampsiaIUGR

HYPERTENSION >Rapid decline in renal function

Preterm labourPreeclampsiaIUGRIncreased perinatal mortality ( from 4% t 23 %)

UTI Pyelonephritis Preterm LabourLow Birth Weight

REDUCED PLASMA VOLUME

IUGR

HYPERGLYCAEMIA Large for gestational age

MANAGEMENT OF WOMEN WITH CKD DURING PREGNANCY

PREPREGNANCYAdvise- Increased risk of Pregnancy complications |( IUGR, Preeclampsia,pretem labour) Adivise – increased risk of deteriorating maternal renal function

Discontinue inappropriate medication- STATINS, ACE INHIBITORS, ARB

Aspirin 75 m/dlFolic acid 5 mg/dl

PRENATAL MONITORING

Urine |Culture every 4-6 weeks- after one infection , keep urine sterile with prophylactic antibiotics

Proteinuria more than 3g/24hr-thrombosis prophylaxis with LMW heparin Proteinuria 1-3g/24hr- prophylaxis if other risk factors ( smoking , matrenal age> 35 yrs,

obesity, immobilty) Haematuria- if red cell cast suggesting active parenchymal disease, consider renal biopsy

or delivery if > 32 weeks Blood Pressure – maintain BP at or below 140/90 mm Hg with antihypertensive

medication Serum Creatinine, BUN- recognise acute or chronic renal impairment and need for dialysis FBC and iron status’-use iron or EPO if necessary to keep Hb 10-11g/dl Baseline renal ultrasound ( pelvicalyceal dimensions)

POST NATAL

Close monitoring of BP and fluid balanceContinue LMW heparin for 6 weeksReturn to nonpregnant medication regimen over 2 weeks

Management of woman on maintainance dialysis during pregnancy

PREGNANCYWoman on dialysis have reduced fertility(0.5—3%)Pregnancy is more likely if optimun Hb and iron statusPregnancy is more likely to be successful with HD rather than PDAdvise increased risk of adverse pregnancy outcome (preterm labour, IUGR and pre-eclampsia)Discontinue inapporporiate medications- statins, ACE inhibitors, ARB

PRENATALHD regimen to mimic physiological renal changes of pregnancy after first trimester increase dialysis regimen to almost daily( 20-24hrs per week) to keep predialysis BUN < 50 mg/dl, serum urea< 17 mmol/L Increase EPO and Iron to keep Hb 10-11g/dlRecognise gestational weight gain, approximately 0.5kg/week in 2nd and 3rd trimsterRecognise hypertension might be caused by fluid overload before using anti-hypertensive medicationGive Aspirin 75 mg and Folic acid 5mg daily throughout pregnancy.Adjust phosphate binders and vitamin D according to serum chemistryAim for protein intake 1.2 to 1.8 g/kg/day LABOUR AND DELIVERYCesarean Section most likelyWomen on PD will need temporary HD ( for 72 hours)

POS TNATALClose monitoring of BP and Fluid balanceGradually return to non-pregnant dialysis regimen over 2 weeks

PREPREGNANCYAdvise to delay pregnancy until 2 years post-transplantationAdvise of increased risk of adverse pregnancy outcome according to BP, proteinuria and GFRDiscontinue and substitute inappropriate medications including statins, ACE inhibitors , ARB, mycophenolate and sirolimus

PRENATALAspirin 75 mg once dailyFolic acid 5mg dailyKeep maintenance CNIs at lower end of therapeutic levelsBe aware of the dilutional fall in CNI levels in pregnancyMonitor BP, renal function, Proteinuria and urine culture every 4-6 weeks throughout pregnancy

MANAGEMENT OF RENAL TRANSPLANT RECEPIENTS DURING PREGNANCY

LABOURperi-partum prophylactic antibioticsSpontaneous vaginal delivery, usually possible despite pelvis kidneyTemporary increase in steroid dose to cover the stress of delivery

POSTNATALre-adjust CNIs dose Breastfeeding while taking azathioprine and cyclosporine unlikely to be harmful but should probably be limited to < one month

GlomerulonephritisClinical parameters like

Hypertension/proteinuria/ development of renal impairment/ UTI more important than histological type

Biopsy- sudden renal impairment with serum creatinine >1.4 mg/dl New onset heavy proteinuria ( >5g/24hrs) Active urinary sediment with red cell cast (32 weeks)

Ig A Nephropathy

Women with normal renal function&BP have successful uncomplicated pregnancy

Pre-existing HT- risk factor for pre-eclampsia and fetal prematurity

ADPKD

High risk for recurrent proteinuria/Hypertension during pregnancy

Pregnancy has triggered recurrent HSP

Reflux Nephropathy1. ComplicationsSuperimposed pre-eclampsiaRecurrent UTIDeteriorating renal functionChronic Hypertension Increased fetal mortality2. Antenatal periodUrine culture every 4-6 weeks throughout

pregnancy3. Women with persistent VUR should be

corrected befire planning for pregnancy.

Upper Urinary Tract ObstructionANTENATAL PERIODRenal function assessmentUrine culture and BPUSG -at end of first trimester repeat if symptoms of infectionor rise

in sr creatinine occurs

LUPUS NEPHRITIS The best outcomes occur in women who have

had stable, inactive lupus for 6 months or longer prior to conception. Renal flares in pregnancy usually present with

proteinuria, hypertension, and falling GFR, making distinction from preeclampsia very difficult. Low complement levels may be helpful in distinguishing between women with preeclampsia and patients with active lupus nephritis.

These patients should all be screened for anti-SSA, due to the risk of congenital heart block

Cont… MANAGEMENT low dose steroids azathioprine hydroxychloroquine relapse- iv methyl prednisolone 500mg daily

for 3 days increased oral prednisolone antihyper tensive low dose aspirin LMWH peripartum flare up - steroids

Diabetic nephropathy Pregnant women with diabetic nephropathy

may also develop worsening proteinuria and hypertension

Complication- preeclampsia still birth good control of blood glucose & blood

pressure before and during pregnancy improves perinatal & maternal out come

Guidelines for pregnancy in kidney transplant recipient: Two years posttransplant, with good general health and serum creatinine less than 2.0

mg/dL (preferably <1.5 mg/dL) No recent or ongoing rejection Normotension, or minimal antihypertensives Absent or minimal proteinuria No evidence of pelvicalyceal dilation on renal ultrasonogram

Immunosuppression Prednisone - Less than 15 mg per day Azathioprine - Less than or equal to 2 mg/kg/d Calcineurin inhibitor–based therapy - Therapeutic levels Mycophenolate mofetil and sirolimus - Discontinue 6 weeks prior to conception Methylprednisolone - The preferred agent for treatment of rejection during pregnancy

Complication Risks Immunosuppressive agents increase the risk of hypertension during pregnancy. Preeclampsia occurs in approximately one-third of transplant recipients. Almost 50% of pregnancies in these women end in preterm delivery due to hypertension. Blood levels of calcineurin inhibitors need to be frequently monitored due to changes in

volumes of distribution of extracellular volume There is an increased risk of cytomegalovirus, toxoplasmosis, and herpes infections, which

arouse concern for the fetus.