31 derebail acute renal failure

Acute Renal Failure for the Acute Renal Failure for the InternIntern

Things to think about before Things to think about before you call that consult…you call that consult…

Vimal Derebail, MDRenal FellowUNC Division of Nephrology and Hypertension

Acute Renal FailureAcute Renal Failure

Is it common enough for me to worry Is it common enough for me to worry about?about?

Of course…Of course…– 1% of all hospital admissions.1% of all hospital admissions.– 10-30% of all ICU admissions.10-30% of all ICU admissions.

Is it really all that bad?Is it really all that bad?– Mortality in all hospitalizations increases.Mortality in all hospitalizations increases.– If dialysis requiring, approaches 40-90%.If dialysis requiring, approaches 40-90%.


Approach to acute renal failure…Approach to acute renal failure…

Classifying the cause:Classifying the cause:– PreRenal (30%).PreRenal (30%).– IntraRenal/Intrinsic cause (65%).IntraRenal/Intrinsic cause (65%).– PostRenal (5%).PostRenal (5%).


Pre-RenalPre-RenalThink of it as anything that reduces renal Think of it as anything that reduces renal perfusion – i.e. altered hemodynamics.perfusion – i.e. altered hemodynamics.– Volume depletion.Volume depletion.– Hypotension.Hypotension.– Cardiovascular (CHF, arrythmias).Cardiovascular (CHF, arrythmias).– Intrarenal vasoconstriction.Intrarenal vasoconstriction.

ACE-I, NSAIDs (inhibit prostaglandin), Ampho B, ACE-I, NSAIDs (inhibit prostaglandin), Ampho B, cyclosporine/tacrolimus, radiographic contrast.cyclosporine/tacrolimus, radiographic contrast.

– HypercalcemiaHypercalcemia– Hepatorenal syndrome.Hepatorenal syndrome.


IntraRenal/Intrinsic CausesIntraRenal/Intrinsic Causes– Vascular – renal infarct, cortical necrosis, Vascular – renal infarct, cortical necrosis,

renal vein thrombosis, malignant HTN, renal vein thrombosis, malignant HTN, scleroderma renal crisis, atheroemboli.scleroderma renal crisis, atheroemboli.

– Tubular injury – ischemic or nephrotoxic.Tubular injury – ischemic or nephrotoxic.– Glomerular – acute GN, vasculitides, TMA.Glomerular – acute GN, vasculitides, TMA.– Interstitial damage – tumor infiltration, Interstitial damage – tumor infiltration,

medication (Acute interstitial nephritis).medication (Acute interstitial nephritis).


Post-Renal CausesPost-Renal Causes

Obstruction…Obstruction…– Prostatic hypertrophy.Prostatic hypertrophy.– Neurogenic bladder.Neurogenic bladder.– Intraureteral obstruction – stones, tumor, clot, Intraureteral obstruction – stones, tumor, clot,

crystals.crystals.– Extraureteral obstruction – extrinsic tumors, Extraureteral obstruction – extrinsic tumors,

retroperitoneal fibrosis.retroperitoneal fibrosis.


Nonoliguric v. Oliguric v. Anuric.Nonoliguric v. Oliguric v. Anuric.What does this mean and why does this matter?What does this mean and why does this matter?Oliguric renal failure.Oliguric renal failure.– Functionally, urine output less than that required to Functionally, urine output less than that required to

maintain solute balance (can’t excrete all solute taken maintain solute balance (can’t excrete all solute taken in).in).

– Defined as urine output < 400ml/24hr.Defined as urine output < 400ml/24hr.

Anuric renal failure.Anuric renal failure.– Defined as urine output < 100ml/24hr.Defined as urine output < 100ml/24hr.– Less common – suggests complete obstruction, major Less common – suggests complete obstruction, major

vascular catastrophy, or more commonly severe ATN.vascular catastrophy, or more commonly severe ATN.


Again, why does this matter?Again, why does this matter?Classifying by urine output may help establish a Classifying by urine output may help establish a cause.cause.– Oliguria – more common with obstruction, prerenal Oliguria – more common with obstruction, prerenal

azotemiaazotemia– Nonoliguric – intrarenal causes – nephrotoxic ATN, Nonoliguric – intrarenal causes – nephrotoxic ATN,

acute GN, AIN.acute GN, AIN.

More importantly, assists in prognosis.More importantly, assists in prognosis.– Significantly higher mortality with oliguric renal failure.Significantly higher mortality with oliguric renal failure.– Approaches 80% in some series.Approaches 80% in some series.– Nonoliguric renal failure may also suggest greater Nonoliguric renal failure may also suggest greater

liklihood of recovery of function.liklihood of recovery of function.


So where do I start?So where do I start?

First question, is it really all acute?First question, is it really all acute?

Difficult to know by labs alone.Difficult to know by labs alone.

Clues to chronic diseaseClues to chronic disease– Pre-existing illness – DM, HTN, age, vascular Pre-existing illness – DM, HTN, age, vascular

disease.disease.– Uremic symptoms – fatigue, nausea, anorexia, Uremic symptoms – fatigue, nausea, anorexia,

pruritis, altered taste sensation (pruritis, altered taste sensation (dysgeusiadysgeusia), hiccups ), hiccups ((singultussingultus).).

– Small, echogenic kidneys by ultrasound.Small, echogenic kidneys by ultrasound.


Yes – it’s acute.Yes – it’s acute.

So what’s next?So what’s next?

The history, of course…The history, of course…– Identify an insultIdentify an insult

Volume depletion (diarrhea, blood loss, emesis, over-Volume depletion (diarrhea, blood loss, emesis, over-diuresis), Hypotension, CHF.diuresis), Hypotension, CHF.

Drug exposure – toxin or reduction of renal perfusion.Drug exposure – toxin or reduction of renal perfusion.

Contrast exposure.Contrast exposure.

Infections – inflammatory mediators v. direct infectionInfections – inflammatory mediators v. direct infection

Endogenous toxins/insults – myoglobin,hemoglobin, uric Endogenous toxins/insults – myoglobin,hemoglobin, uric acid.acid.

Acute Renal FAilureAcute Renal FAilure

Symptoms:Symptoms:– Fever, rash, joint pains, myalgiasFever, rash, joint pains, myalgias

Concern for SLE, vasculitis, acute interstitial Concern for SLE, vasculitis, acute interstitial nephritis.nephritis.

– Dyspnea – heart failure.Dyspnea – heart failure.– Hemoptysis – Goodpasture’s, Wegener’s.Hemoptysis – Goodpasture’s, Wegener’s.– Preceding bloody diarrhea – HUS.Preceding bloody diarrhea – HUS.– Preceding pharyngitis – post-Strep GN, post-Preceding pharyngitis – post-Strep GN, post-

infectious GN.infectious GN.


Urine output.Urine output.– Abrupt anuria.Abrupt anuria.

Acute obstruction, severe acute GN, sudden Acute obstruction, severe acute GN, sudden vascular catastrophe.vascular catastrophe.

– Slowly diminishing.Slowly diminishing.Ureteral stricture.Ureteral stricture.Prostatic enlargement.Prostatic enlargement.

– Presence of hematuriaPresence of hematuriaPainless – suggests GN.Painless – suggests GN.Painful – suggest ureteral obstruction.Painful – suggest ureteral obstruction.


Physical Exam.Physical Exam.– Skin – new rashes.Skin – new rashes.

Livedo reticularis – atheroemboli, SLE, cryoglobulins.Livedo reticularis – atheroemboli, SLE, cryoglobulins.

Petechiae – HSP.Petechiae – HSP.

Malar rash – SLE.Malar rash – SLE.

– ExeExePapilledema – malignant HTN.Papilledema – malignant HTN.

Roth’s spots – endocarditis.Roth’s spots – endocarditis.

– CVCVRub – suggestive of uremic pericarditis, lupus.Rub – suggestive of uremic pericarditis, lupus.

Gallop – suggesting CHF.Gallop – suggesting CHF.


Physical Exam.Physical Exam.– Assessing volume status.Assessing volume status.

Is the patient intravascularly volume depleted?Is the patient intravascularly volume depleted?– Neck veins – JVPNeck veins – JVP– Peripheral edema or lack of.Peripheral edema or lack of.– Orthostatic vitals.Orthostatic vitals.

– Not always straightforward.Not always straightforward.– Pt. may be edematous (low albumin) or have Pt. may be edematous (low albumin) or have

significant right sided heart disease.significant right sided heart disease.


Diagnostic studies.Diagnostic studies.BUN/Creatinine ratio.BUN/Creatinine ratio.– > 20:1 – suggest prerenal or obstruction.> 20:1 – suggest prerenal or obstruction.– Can be elevated by anything leading to increased Can be elevated by anything leading to increased

urea production/absorption.urea production/absorption.GI bleedGI bleedTPNTPNSteroidsSteroidsDrugs – Tigecycline.Drugs – Tigecycline.

Creatinine in anephric state typically only rises Creatinine in anephric state typically only rises 1mg/dl/day.1mg/dl/day.– If greater – should be concerned for rhabdomyolysis.If greater – should be concerned for rhabdomyolysis.


Urine ElectrolytesUrine Electrolytes

FEFENaNa – fractional excretion of sodium. – fractional excretion of sodium.

– FEFENa Na = = UrineUrineNa Na x Plasmax PlasmaCrCr

X X 100.100.

UrineUrineCr Cr x Plasma x PlasmaNa.Na.


FEFENaNa

– < 1% suggestive of prerenal cause.< 1% suggestive of prerenal cause.– > 2% suggestive of ATN/tubular damage.> 2% suggestive of ATN/tubular damage.– Not quite so clear cut – low FENot quite so clear cut – low FENa Na seen in other causes seen in other causes

of renal failure.of renal failure.Nonoliguric ATN.Nonoliguric ATN.Radiocontrast nephropathy.Radiocontrast nephropathy.Acute GN.Acute GN.Acute interstitial nephritis.Acute interstitial nephritis.

– Not as helpful in setting of diuretics.Not as helpful in setting of diuretics.Can use FECan use FEUreaUrea

< 35% suggests prerenal cause.< 35% suggests prerenal cause.

Acute Renal FailureAcute Renal FailureIndexIndex Pre-RenalPre-Renal ATNATN

UrineUrineNaNa <20 mEq/L<20 mEq/L >40 mEq/L>40 mEq/L

FEFENaNa <1%<1% ≥≥1%1%

FEFEUreaUrea <35%<35% >50%>50%

BUN/CreatinineBUN/Creatinine >20:1>20:1 ≤≤20:120:1

UrineUrineCrCr./Plasma./PlasmaCr.Cr. >40>40 <20<20


SPEP/UPEPSPEP/UPEP

ANAANA

ANCAANCA

Hepatitis B and CHepatitis B and C

HIVHIV

Uric AcidUric Acid

CryoglobulinsCryoglobulins

Complement levels Complement levels (C3, C4)(C3, C4)

CKCK

Peripheral smearPeripheral smear

Other Labs we like to order…


Imaging…Imaging…– Renal U/S – we Renal U/S – we ALWAYSALWAYS like to see one. like to see one.

Rules out obstruction.Rules out obstruction.

Evaluates chronicity – small size, echogenic.Evaluates chronicity – small size, echogenic.

Makes sure there are 2 kidneys.Makes sure there are 2 kidneys.

– MRA or Doppler U/S may be useful in looking MRA or Doppler U/S may be useful in looking for renal artery stenosis.for renal artery stenosis.


Don’t forget the urine sediment!Don’t forget the urine sediment!

Can be helpful in identifying underlying Can be helpful in identifying underlying disease states (proteinuric disease, disease states (proteinuric disease, underlying chronic GN) as well as underlying chronic GN) as well as examining acute insult.examining acute insult.

Acute Renal failureAcute Renal failureIntroduction to casts…Introduction to casts…

Hyaline Casts:

Better seen with low light.

Non-specific.

Composed of Tamm-Horsfall mucoprotein.


UpToDate Images.

Waxy Casts:

Smooth appearance.

Blunt ends.

May have a “crack”.

Felt to be last stage of degenerating cast – representative of chronic disease.

Granular Casts:

Represent degenerating cellular casts or aggregated protein.

Nonspecific.

Acute Renal FailureAcute Renal FailureFatty Casts:

Seen in patients with significant proteinuria.

Refractile in appearance.

May be associated with free lipid in the urine.

Can see also “oval fat bodies” – RTE’s that have ingested lipid.

Polarize – demonstrate “Maltese cross”.

UpToDate Images.


Muddy Brown Casts:

Highly suggestive of ATN.

Pigmented granular casts as seen in hyperbilirubinemia can be confused for these.

UpToDate Images.


UpToDate Images.

White Blood Cell Casts:

Raises concern for interstitial nephritis.

Can be seen in other inflammatory disorders.

Also seen in pyelonephritis.

Acute Renal FailureAcute Renal FailureHematuriaHematuria

Nonglomerular hematuria:

Urologic causes.

Bladder/Foley trauma.

Nephrolithiasis.

Urologic malignancy.

May be “crenated” based upon age of urine, osmolality – NOT dysmorphic.


Red Blood Cell Casts:

Essentially diagnostic of vasculitis or glomerulonephritis.

Dysmorphic Red Cells:

Suggestive of glomerular bleeding as seen with glomerulonephritis.

Blebs, buds, membrane loss.

Rarely reported in other conditions – DM, ATN.

Acute Renal FailureAcute Renal FailureCrystals – Pretty and important.

Uric acid crystals:

Seen in any setting of elevated uric acid and an acidic urine.

Seen with tumor lysis syndrome.

Calcium oxalate crystals:Monohydrate – dumbell shaped, may be needle-like.Dihydrate – envelope shaped.Form independent of urine pH.Seen acutely in ethylene glycol ingestion.

UpToDate Images.


Prerenal AzotemiaPrerenal Azotemia– Decreased renal blood flow – usually with Decreased renal blood flow – usually with

afferent arteriolar vasoconstriction.afferent arteriolar vasoconstriction.– Bland urine sediment – may see hyaline Bland urine sediment – may see hyaline

casts.casts.– Low FENa, high BUN/Cr. Ratio.Low FENa, high BUN/Cr. Ratio.– Tx – volume repletion, inotropes in CHF.Tx – volume repletion, inotropes in CHF.


ATNATN– Usually after ischemic, toxic insult.Usually after ischemic, toxic insult.– Tubular necrosis leads to sloughing of tubular Tubular necrosis leads to sloughing of tubular

cells into the lumen leading to obstruction of cells into the lumen leading to obstruction of flow.flow.

– Sediment – RTE’s, granular casts.Sediment – RTE’s, granular casts.– Classic “muddy brown casts”.Classic “muddy brown casts”.– FENa >2% typically.FENa >2% typically.– Treatment – correcting underlying cause if Treatment – correcting underlying cause if

possible, otherwise supportive.possible, otherwise supportive.


GlomerulonephritisGlomerulonephritis– Always think about this at UNC.Always think about this at UNC.– Several forms – ANCA, cell mediated, Ab Several forms – ANCA, cell mediated, Ab

associated, Immune complex mediated (SLE).associated, Immune complex mediated (SLE).– Dysmorphic hematuria, RBC casts.Dysmorphic hematuria, RBC casts.– Some degree of proteinuria.Some degree of proteinuria.


Acute Interstitial NephritisAcute Interstitial Nephritis– Typically rapid decline in function.Typically rapid decline in function.– May have associated fever, rash, arthralgias.May have associated fever, rash, arthralgias.– Peripheral eosinophlia.Peripheral eosinophlia.– Hansel’s stain for urine may be helpful.Hansel’s stain for urine may be helpful.– Urine sediment – Wbc’s and/or wbc casts.Urine sediment – Wbc’s and/or wbc casts.– Tx – removal of offending agent, +/- steroids.Tx – removal of offending agent, +/- steroids.


RhabdomyolysisRhabdomyolysis– Causes – trauma, exertion, medications, Causes – trauma, exertion, medications,

hypoxemia, hereditary disorders.hypoxemia, hereditary disorders.– TreatmentTreatment

Aggressive hydrationAggressive hydration

Alkalinazation/mannitol controversial.Alkalinazation/mannitol controversial.

May see hyperkalemia, hypocalcemia.May see hyperkalemia, hypocalcemia.


Cholesterol EmboliCholesterol Emboli– Risk factors:Risk factors:

Aortic surgery.Aortic surgery.

Angiography, cardiac catheterization.Angiography, cardiac catheterization.

Balloon pump.Balloon pump.

Thrombolytics.Thrombolytics.

– Peripheral eosinophilia.Peripheral eosinophilia.– Livedo reticularis.Livedo reticularis.– Hypocomplementemia.Hypocomplementemia.


Drugs:Drugs:– Prerenal – cyclosporine, tacrolimus, contrast, Prerenal – cyclosporine, tacrolimus, contrast,

ACE-I, ampho B, NSAIDs.ACE-I, ampho B, NSAIDs.– ATN – AG’s, ampho B, cisplatinATN – AG’s, ampho B, cisplatin– AIN – PCN, cephalosporins, sulfa drugs, AIN – PCN, cephalosporins, sulfa drugs,

rifampin, NSAIDs, interferon, quinolones.rifampin, NSAIDs, interferon, quinolones.– Post-Renal – acyclovir, indinavir, analgesics.Post-Renal – acyclovir, indinavir, analgesics.


Contrast Nephropathy.Contrast Nephropathy.– Risk factorsRisk factors

DM.DM.Pre-existing renal disease.Pre-existing renal disease.Severe CHF.Severe CHF.Volume depletion.Volume depletion.Myeloma.Myeloma.Elderly.Elderly.Contrast volume.Contrast volume.Coadministration of other nephrotoxin.Coadministration of other nephrotoxin.


Contrast nephropathy.Contrast nephropathy.– Prevention – volume expansion – isotonic Prevention – volume expansion – isotonic

saline v. bicarbonatesaline v. bicarbonate– NAC, theophylline less convincing.NAC, theophylline less convincing.– Hemofiltration studied – impractical, poor Hemofiltration studied – impractical, poor

evidence.evidence.


Hepatorenal syndromeHepatorenal syndrome – – major criteria.major criteria.– Chronic or acute liver disease with advanced hepatic failure and portal Chronic or acute liver disease with advanced hepatic failure and portal

hypertensionhypertension– Low GFR, as indicated by a serum creatinine >1.5 mg/dL or a creatinine Low GFR, as indicated by a serum creatinine >1.5 mg/dL or a creatinine

clearance < 40 mL/minclearance < 40 mL/min– Absence of shock, ongoing bacterial infection, fluid loss, and current or Absence of shock, ongoing bacterial infection, fluid loss, and current or

recurrent treatment with nephrotoxic drugs. Absence of gastrointestinal recurrent treatment with nephrotoxic drugs. Absence of gastrointestinal fluid losses (repeated vomiting or intense diarrhea) or renal fluid losses fluid losses (repeated vomiting or intense diarrhea) or renal fluid losses (as indicated by weight loss > 500 gm/d for several days in patients with (as indicated by weight loss > 500 gm/d for several days in patients with ascites without peripheral edema or > 100 gm/d in patients with ascites without peripheral edema or > 100 gm/d in patients with peripheral edema)peripheral edema)

– No sustained improvement in renal function (decrease in serum No sustained improvement in renal function (decrease in serum creatinine to 1.5 mg/dL or less or increase in creatinine clearance to 40 creatinine to 1.5 mg/dL or less or increase in creatinine clearance to 40 ml/min or more) after withdrawal of diuretics and expansion of plasma ml/min or more) after withdrawal of diuretics and expansion of plasma volume with 1.5 L of isotonic salinevolume with 1.5 L of isotonic saline

– Proteinuria < 500 mg/d and ultrasonographic evidence of obstructive Proteinuria < 500 mg/d and ultrasonographic evidence of obstructive uropathy or parenchymal renal disease.uropathy or parenchymal renal disease.


Hepatorenal Syndrome – minor criteria.Hepatorenal Syndrome – minor criteria.– Urine volume < 500 mL/dayUrine volume < 500 mL/day– Urine sodium < 10 mEq/LUrine sodium < 10 mEq/L– Urine osmolality > plasma osmolalityUrine osmolality > plasma osmolality– Urine red blood cells < 50 per high-power fieldUrine red blood cells < 50 per high-power field– Serum sodium concentration < 130 mEq/LSerum sodium concentration < 130 mEq/L

31 derebail acute renal failure

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