Post on 07-Apr-2018
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Acute Renal FailureAcute Renal Failure
By Abhishek JaguessarBy Abhishek Jaguessar
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ARF is anARF is an ABRUPT & RAPIDABRUPT & RAPID
decline in thedecline in the GFRGFR,, not necessarilynot necessarilyaccompanied by a decrement in urine output oraccompanied by a decrement in urine output or
by compromise in tubular function, butby compromise in tubular function, but
associated with aassociated with a PROGRESSIVE &PROGRESSIVE &
DETECTABLEDETECTABLE increment in serumincrement in serum
creatininecreatinine overover hours to dayshours to days, but, but
sometimessometimes weeksweeks..
Dr. Mortimer Levy, 2003Dr. Mortimer Levy, 2003
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AZOTEMIAAZOTEMIA is the state where excessis the state where excessurea and other nitrogenous wastes isurea and other nitrogenous wastes is
found in the blood, whereasfound in the blood, whereas UREMIAUREMIA
is theis the symptomaticsymptomatic condition that resultscondition that results
from excess urea and other nitrogenousfrom excess urea and other nitrogenous
wastes in the blood and is associatedwastes in the blood and is associated
with other electrolyte and endocrinewith other electrolyte and endocrine
abnormalities of renal dysfunction.abnormalities of renal dysfunction.
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NONNON--OLIGURICOLIGURIC > 400 mL urine output in 24 h> 400 mL urine output in 24 h
OLIGURICOLIGURIC < 400 mL urine output in 24 h< 400 mL urine output in 24 h
ANURICANURIC < 100 mL urine output in 24 h< 100 mL urine output in 24 h
Clinical Description of Acute Renal FailureClinical Description of Acute Renal Failure
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Determinants of GFRDeterminants of GFR
GFR
GFR= LGFR= LPPA x (A x (((PP -- (T(T))
LLPPAA = ultrafiltration= ultrafiltration
coefficientcoefficient
(hydraulic permeability &(hydraulic permeability &glomerular membraneglomerular membrane
surface area)surface area)((PP == PPGCGC PPPTPT(hydrostatic pressure(hydrostatic pressure
difference between the glomerulardifference between the glomerular
capillary & Bowmans space)capillary & Bowmans space)
(T(T == TTGCGC TTPTPT(oncotic pressure difference between the(oncotic pressure difference between the
glomerular capillary & Bowmans space)glomerular capillary & Bowmans space)
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Pathophysiology of ARFPathophysiology of ARF
GFR= LGFR= LPPA x [(A x [(PPGCGC PPPTPT)) ((TTGCGC TTPTPT)])]
LLPPAA Glomerular disease & drugs viaGlomerular disease & drugs via
unknown mechanism but associatedunknown mechanism but associated
with mesangial cell contractionwith mesangial cell contraction
PPGCGC qqRenal arterial pressureRenal arterial pressureooAfferentAfferent--arteriolar resistancearteriolar resistance
qq EfferentEfferent--arteriolar resistancearteriolar resistance
PPBCBC oo Intratubular pressure from tubular orIntratubular pressure from tubular or
extraextra--renal urinary system obstructionrenal urinary system obstruction
TTGCGC oo System plasma oncotic pressureSystem plasma oncotic pressureqq Renal plasma flowRenal plasma flow
Intrarenal vasoconstriction is the major mechanism ofIntrarenal vasoconstriction is the major mechanism ofqq GFR inGFR in
ARF, and stressed renal microvasculature is more sensitive toARF, and stressed renal microvasculature is more sensitive to
further hypotensive insults.further hypotensive insults.
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Assessing the Severity of ARFAssessing the Severity of ARF
A Creatinine rise fromA Creatinine rise from
90 to 12090 to 120 QQM results inM results ina GFR decline from ~a GFR decline from ~
135135 ml/minml/min to ~ 95to ~ 95 ml/minml/min, a, a
drop ofdrop of30 %30 %
A Creatinine rise fromA Creatinine rise from
190 to 240190 to 240 QQM resultsM resultsin a GFR decline fromin a GFR decline from
~ 52~ 52 ml/minml/min to ~ 47to ~ 47 ml/minml/min,,
a drop ofa drop of10 %10 %
Similar decrements in serum Creatinine at lower values resultSimilar decrements in serum Creatinine at lower values result
in more significant changes in GFRthan the same decrementin more significant changes in GFRthan the same decrement
at higher values.at higher values.
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Distinguishing ARF from CRFDistinguishing ARF from CRF
Helpful cluesHelpful clues
Previous creatinine valuesPrevious creatinine values
HbHb anemia suggests chronic problemanemia suggests chronic problem
Renal ultrasoundRenal ultrasound small, echogenic kidneys suggest asmall, echogenic kidneys suggest a
chronic problemchronic problem
XX--raysrays renal osteodystrophy suggests chronic problemrenal osteodystrophy suggests chronic problem
Renal biopsyRenal biopsy
Exceptions to the small kidneys = CRF rule:Exceptions to the small kidneys = CRF rule:
early DM, amyloid, HIV nephropathy, PCKDearly DM, amyloid, HIV nephropathy, PCKD
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WhatWhat
causes it?causes it?
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The ARF ParadigmThe ARF Paradigm
1. Pre-renal
2. IntrinsicRenal
3. Post-renal
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1. Pre-renal
2. IntrinsicRenal
3. Post-renal
Pre-renal ARF
qq Renal PerfusionRenal Perfusion
Renal losses: diuretics,Renal losses: diuretics,
osmotic diuresis, etcosmotic diuresis, etc
ExtraExtra--renal losses:renal losses:
vomiting, diarrhea,vomiting, diarrhea,
skinskin
Volume Depletion qArterial Volume Renal Vasoconstricn
Cardiogenic (CHF,Cardiogenic (CHF,
ACS, arrhythmias,ACS, arrhythmias,
shock)shock)
Septic shockSeptic shock
Hepatorenal syndromeHepatorenal syndrome
Adrenal insufficiencyAdrenal insufficiency
RadiocontrastRadiocontrast
Prostaglandin inhibitionProstaglandin inhibition
Calcinurin inhibitorsCalcinurin inhibitors
ACE inhibitorsACE inhibitors
Amphotericin BAmphotericin B
When autoregulatory mechanisms are maximized, any smallWhen autoregulatory mechanisms are maximized, any small
renal insult will subsequently precipitate acute renal failure.renal insult will subsequently precipitate acute renal failure.
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1. Pre-renal
2. IntrinsicRenal
3. Post-renal
Intrinsic
Renal A
RF
1
2
Glomerular
Tubulointerstitial
3 Vascular
Though in all cases of intrinsic renal failure the kidney is the site of pathology,Though in all cases of intrinsic renal failure the kidney is the site of pathology,
determining the nature of the problem is critical sincedetermining the nature of the problem is critical since TREATMENT&& PROGNOSIS
vary considerably.vary considerably.
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1 Glomerular NEPHROTIC NEPHRITIC
Diabetes Amyloidosis
Minimal Change Membranous IgA Nephropathy RPGN
FSGS MPGN I & II
Rapidly Progressive GlomerulonephritisRapidly Progressive Glomerulonephritis
AntiAnti--GMB DiseasesGMB Diseases Immune ComplexImmune Complex PauciPauci--immune/ANCAimmune/ANCA
GoodpasturesGoodpastures
SyndromeSyndrome
AntiAnti--GBM nephritisGBM nephritis
SLESLE
IgAIgA
CryoglobulinemiaCryoglobulinemia
Infectious (hepatitis B/C,Infectious (hepatitis B/C,
postpost--streptococcal,streptococcal,
endocarditis)endocarditis)
WegenersWegeners
GranulomatosisGranulomatosis
Microscopic PolyangiitisMicroscopic Polyangiitis
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2 Tubulointerstitial
InterstitialInterstitial
TubularTubular
Acute TubularN
ecrosis (ATN)Acute Tubular
Necrosis (AT
N)
~ 45 % ARF in hospitalized patients is~ 45 % ARF in hospitalized patients is
from ATNfrom ATN
Ischemic ATNIschemic ATN
Nephrotoxic ATNNephrotoxic ATN
Most commonMost common
Often following prolonged hypoperfusionOften following prolonged hypoperfusion
DrugsDrugs: aminoglycosides, amphotericin B,: aminoglycosides, amphotericin B,
chemotherapeutic agentschemotherapeutic agents
Endogenous toxinsEndogenous toxins: hemoglobin, myoglobin,: hemoglobin, myoglobin,
light chainslight chains
Acute InterstitialNephritis (AIN)Acute InterstitialNephritis (AIN)~ 30 % AIN associated with systemic Sx~ 30 % AIN associated with systemic Sx
of fevers, arthralgias, maculopapularof fevers, arthralgias, maculopapular
erythematous rash & eosinophiliaerythematous rash & eosinophilia
DrugsDrugs: penicillins, cephalosporins, NSAIDs,: penicillins, cephalosporins, NSAIDs,
sufonamide analoguessufonamide analogues
InfectionsInfections: renal parenchymal or systemic: renal parenchymal or systemic
Immunologic disordersImmunologic disorders: SLE, Sjorgrens,: SLE, Sjorgrens,
mixed cryoglobulinemiamixed cryoglobulinemia
IdiopathicIdiopathic: 10: 10 20 % of Bx20 % of Bx--proven AINproven AIN
Obstructive NephropathyObstructive NephropathyHeme pigmentsHeme pigments
Myeloma proteinsMyeloma proteins
Drug crystalsDrug crystals
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3 Vascular
MacrovascularMacrovascular
MicrovascularMicrovascular
Malignant hypertensionMalignant hypertension
Scleroderma crisisScleroderma crisis
Cholesterol emboli syndromeCholesterol emboli syndrome
VasculitisVasculitis
Microangiopathy (HUS/TTP)Microangiopathy (HUS/TTP)
PrePre--eclampsia/eclampsiaeclampsia/eclampsia
Hyperviscosity syndromeHyperviscosity syndrome
Macrovascular causes of ARFmust affect both kidneys in theMacrovascular causes of ARFmust affect both kidneys in theabsence of a solitary kidney or significantly diseased contralateralabsence of a solitary kidney or significantly diseased contralateral
kidney.kidney.
Renal artery stenosisRenal artery stenosis
Renal vein thrombosisRenal vein thrombosis
Renal infarctionRenal infarction
TumorTumor
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1. Pre-renal
2. IntrinsicRenal
3. Post-renal
Post-renal ARF
ObstructionObstruction
CrystalsCrystals
StonesStones
ClotsClots
TumorTumor
Papillary necrosisPapillary necrosis
Ureteral Urethral Retroperitoneal
ClotsClots
TumorTumor
ProstateProstate
EndometrialEndometrial
Neurogenic bladderNeurogenic bladder
FibosisFibosis
PostPost--renal causes of ARFmust result from bilateral kidney/ureteralrenal causes of ARFmust result from bilateral kidney/ureteral
obstruction, or obstruction in the lower urinary tract, in the absenceobstruction, or obstruction in the lower urinary tract, in the absence
of a solitary kidney or significantly diseased contralateral kidney.of a solitary kidney or significantly diseased contralateral kidney.
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1. Pre-renal
2. IntrinsicRenal
3. Post-renal
qq Renal PerfusionRenal Perfusion
ObstructionObstruction
GlomerularGlomerular
TubularTubular
InterstitialInterstitial
VascularVascular
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HowdoweHowdowe
diagnose it?diagnose it?
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History & Physical Will Guide DDxHistory & Physical Will Guide DDx
Primer on Kidney Diseases 3Primer on Kidney Diseases 3rdrdEd. pg 248.Ed. pg 248.
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Basic Initial InvestigationsBasic Initial Investigations
Foley catheter maybeFoley catheter maybe
Ultrasound to evaluate kidneys + GU tractUltrasound to evaluate kidneys + GU tract
UrinalysisUrinalysis
Urine cultureUrine culture
24h urine collection for CrCl and proteinuria24h urine collection for CrCl and proteinuria
Basic electrolytes, Ca/PO4 + acid/base statusBasic electrolytes, Ca/PO4 + acid/base status
Consideration for dialysisConsideration for dialysis
Other investigations guided by DDx immunologicOther investigations guided by DDx immunologicpot pourripot pourri
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The Value of UrinalysisThe Value of Urinalysis
PrePre--renalrenal
Intrinsic renalIntrinsic renal
GlomerularGlomerular
ATNATN
AINAIN
PostPost--renalrenal
UrinalysisUrinalysis
High specific gravity, normal or hyaline castsHigh specific gravity, normal or hyaline casts
Proteinuria, hematuria, RBC castsProteinuria, hematuria, RBC casts
Low specific gravity, muddy brown casts, tubular epithelial cellsLow specific gravity, muddy brown casts, tubular epithelial cells
Mild proteinuria, hematuria, WBC, WBC casts, eosinophilsMild proteinuria, hematuria, WBC, WBC casts, eosinophils
Normal or hematuria, WBC, occasional granular castsNormal or hematuria, WBC, occasional granular casts
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PrePre--renalrenal vs.vs. ATNATN
Creatinine:Urea ratioCreatinine:Urea ratio
UNaUNa
UosmUosm
FENaFENa
U specific gravityU specific gravity
UrinalysisUrinalysis
FavoursFavours
PrePre--renalrenal
FavoursFavours
ATNATN
> 20:1> 20:1
< 20< 20
> 500 mO/kg> 500 mO/kg
< 1 %< 1 %
> 1.018> 1.018
Normal or hyalineNormal or hyaline
castscasts
40
~ isotonic~ isotonic
> 2 %> 2 %
< 1.010< 1.010
Tubular cells & muddyTubular cells & muddy
brown granular castsbrown granular casts
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Fractional Excretion of Substance XFractional Excretion of Substance X
FEFEXX= the proportion of the filtered mass of = the proportion of the filtered mass of XX that is excreted that is excreted
FEFEXX= mass excreted= mass excreted
mass filteredmass filteredFEFEXX= U= UXXx VV
GFRGFRx PPXX
FEFEXX= U= UXXx VVPPXX UUCrCr x VV
PPCrCr
FEFEXX= U= UXXx PPCrCrPPXXx UUCrCr
= U= U/P/PXXUU/P/P CrCr
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When Should Biopsy be ConsideredWhen Should Biopsy be Considered
ASYMPTOMATICHEMATURIAASYMPTOMATICHEMATURIA(red cell casts or dysmorphic(red cell casts or dysmorphicRBCs)RBCs) PROTEINURIAPROTEINURIA
NEPHRITICSYNDROMENEPHRITICSYNDROME(HTN, hematuria, C3/4,(HTN, hematuria, C3/4, proteinuria)proteinuria)
RAPIDLYPROGRESSGLOMERULONEPHRITISRAPIDLYPROGRESSGLOMERULONEPHRITIS
NEPHROTICSYNDROMENEPHROTICSYNDROME (proteinuria, edema, dyslipidemia,(proteinuria, edema, dyslipidemia,hypoalbuminemia)hypoalbuminemia) except in children
ACUTERENAL FAILUREACUTERENAL FAILURE(not known to be pre(not known to be pre--renal or postrenal or post--renal)renal)
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Indications for DialysisIndications for Dialysis
HYPERKALEMIAHYPERKALEMIAnot amenable to medical therapynot amenable to medical therapy
ACIDOSISACIDOSIS not amenable to medical therapynot amenable to medical therapyUREMIAUREMIAresulting in pericarditis, neuropathy orresulting in pericarditis, neuropathy or
encephalopathyencephalopathy
CriticalCriticalVOLUMEOVERLOADVOLUMEOVERLOAD not responsive to diuresisnot responsive to diuresis
(dialyzable drug intoxication)(dialyzable drug intoxication)
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