Acute Renal Failure (Clinical Clerks) by Abhishek Jaguessar

8/4/2019 Acute Renal Failure (Clinical Clerks) by Abhishek Jaguessar

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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


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


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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Acute Renal Failure (Clinical Clerks) by Abhishek Jaguessar