Acute Renal FailureAcute Renal Failure::A ReviewA Review

Bradley J. Phillips, M.D.Bradley J. Phillips, M.D.

Burn-Trauma-ICUBurn-Trauma-ICU

Adults & PediatricsAdults & Pediatrics

Renal Function and FailureRenal Function and Failure

OverviewOverview Renal PhysiologyRenal Physiology Trauma and Renal FunctionTrauma and Renal Function Initial management of OliguriaInitial management of Oliguria Acute Renal FailureAcute Renal Failure Key Management IssuesKey Management Issues

Glomerular Glomerular ArchitecturArchitectur

ee

Physiology in Normal StatePhysiology in Normal State

Renal blood flow (RBF)Renal blood flow (RBF) 20-25% cardiac output 20-25% cardiac output distributiondistribution

• 85% outer cortical 85% outer cortical

• 15% inner cortex 15% inner cortex outer medullaouter medulla

• <1% inner medulla<1% inner medulla

Physiology in Normal StatePhysiology in Normal State

Glomerular filtrationGlomerular filtration 20% of plasma filtered as cell-free and 20% of plasma filtered as cell-free and

protein-free protein-free normal GFR 125 ml/minnormal GFR 125 ml/min calculatecalculate

• most accurate - insulinmost accurate - insulin completely filtered/neither secreted or absorbedcompletely filtered/neither secreted or absorbed

• good estimation - creatininegood estimation - creatinine (Cr (Cr UrineUrine / Cr / Cr PlasmaPlasma) x urine (ml/min)) x urine (ml/min)

Glomerular Component Glomerular Component FunctionsFunctions

Proximal Convoluted Tubule 60-80% reabsoprtion of H2O,

Na, Cl, K, HCO3 100% glucose/amino acids

Distal Convoluted Tubule 20% reabsoprtion of H2O

Renin/Aldosterone Effect

Collecting Ducts reabsoprtion of H2O, ADH effect

Loops of Henle 20% of H2O (descending), 25% Na, Cl, K, Large amounts HCO3, Mg, Cl

Secretion of H ions, Active Na Reabsorption

Renal Physiology after Renal Physiology after TraumaTrauma

Class I Hemorrhage (10-15%)Class I Hemorrhage (10-15%) autoregulation maintains GFRautoregulation maintains GFR

Class II Hemorrhage (15-30%)Class II Hemorrhage (15-30%) exceeds autoregulationexceeds autoregulation vasoconstriction at afferent & efferentvasoconstriction at afferent & efferent GFR decreases by 50-60%GFR decreases by 50-60%

Class III Hemorrhage (30-40%)Class III Hemorrhage (30-40%) GFR decreases to less than 20%GFR decreases to less than 20%

resuscitation relieves vasocontriction over hours to days,

afferent then efferent arterioles

Oliguria after TraumaOliguria after Trauma

Rapid replenishment of the circulatory Rapid replenishment of the circulatory volume and cardiac outputvolume and cardiac output at least 3-4 L for every 1 L of blood lossat least 3-4 L for every 1 L of blood loss

FactorsFactors general anestheticgeneral anesthetic

• loss of renal autoregulationloss of renal autoregulation• loss of systemic vasoconstrictionloss of systemic vasoconstriction

Key Management IssueKey Management Issue

IV Fluid ResuscitationIV Fluid Resuscitation

Renal Function and TraumaRenal Function and Trauma

Postresuscitative oliguriaPostresuscitative oliguria even if MAP and CO restoredeven if MAP and CO restored persistant for several hours secondary to renal arteriole persistant for several hours secondary to renal arteriole

vasoconstrictionvasoconstriction shifting of fluid from plasma to interstitial space shifting of fluid from plasma to interstitial space

secondary to depletion during hypotension/hypovolemiasecondary to depletion during hypotension/hypovolemia

Postresuscitative polyuriaPostresuscitative polyuria usually transientusually transient not excessive not excessive (< 250 cc for 30-45 mins, < 3 hrs)(< 250 cc for 30-45 mins, < 3 hrs) ““wash out” effect of inner medullawash out” effect of inner medulla use other parameters use other parameters ( i.e. HR, base deficit)( i.e. HR, base deficit)

Postoperative Fluid Postoperative Fluid SequestrationSequestration

Obligatory extravascular sequestrationObligatory extravascular sequestration Phase II Phase II (Lucas, Resuscitation of the Injured Patient: Three Phases of (Lucas, Resuscitation of the Injured Patient: Three Phases of

Resuscitation, Surg Clin North Am, 1977)Resuscitation, Surg Clin North Am, 1977)

Lasts 12-36 hoursLasts 12-36 hours Clinical signsClinical signs

tachycardiatachycardia reduced pulse pressurereduced pulse pressure oliguriaoliguria weight gainweight gain some respiratory insufficiencysome respiratory insufficiency

Hormoral effect - ADH, aldosteroneHormoral effect - ADH, aldosterone

Fluid Mobilization PhaseFluid Mobilization Phase Phase III - mobilization and diuresisPhase III - mobilization and diuresis Water added to plasma faster than Water added to plasma faster than

excretedexcreted ““Postresuscitation Hypertension”Postresuscitation Hypertension” Renal blood flow still remains decreasedRenal blood flow still remains decreased Caution with diureticsCaution with diuretics

role in post elective surgery in elderly patient with role in post elective surgery in elderly patient with CHFCHF

avoid in trauma patientsavoid in trauma patients can precipitate oliguria/renal dysfunctioncan precipitate oliguria/renal dysfunction

Mechanical Ventilation and Mechanical Ventilation and Fluid TherapyFluid Therapy

Reduce renal blood flowReduce renal blood flow even if zero PEEPeven if zero PEEP PEEP reduces RBF morePEEP reduces RBF more additional fluid may be required to additional fluid may be required to

maintain UOPmaintain UOP

Acid-Base Balance Acid-Base Balance

Hemorrhagic shockHemorrhagic shock increased lactate acidosisincreased lactate acidosis metabolic acidosis persistent after intravascular volume metabolic acidosis persistent after intravascular volume

repleted (hours)repleted (hours)• cell metabolismcell metabolism• impaired renal excretion of acidsimpaired renal excretion of acids

Renal acid excretionRenal acid excretion absorb Na/HCOabsorb Na/HCO33, excrete PO, NH, excrete PO, NH33

normal excrete 70-80 mEq /daynormal excrete 70-80 mEq /day can excrete 4-5x normal with severe acidosiscan excrete 4-5x normal with severe acidosis depends on GFR and RBFdepends on GFR and RBF

Renal Response to SepsisRenal Response to Sepsis

Hyperdynamic stateHyperdynamic state increased CO, increased RBF, decreased SVR, increased CO, increased RBF, decreased SVR,

expanded ECF volume, increased UOPexpanded ECF volume, increased UOP ““inappropriate polyuria”inappropriate polyuria”

• vasodilators of sepsisvasodilators of sepsis• ““wash out” effectwash out” effect

Hypodynamic stateHypodynamic state later stages of severe sepsislater stages of severe sepsis decreased CO, increased SVR, decreased GFR decreased CO, increased SVR, decreased GFR

and RBFand RBF

Key Management IssueKey Management Issue

IV Fluid ResuscitationIV Fluid Resuscitation

PEARL: Check Urine Na.

If less than 10 meq/L…???

Acute Renal FailureAcute Renal Failure

Mortality in posttrauma = 50- 60%Mortality in posttrauma = 50- 60% acute oliguric > 90%acute oliguric > 90% contrast nonoliguric < 20%contrast nonoliguric < 20%

TerminologyTerminology ARF - ARF - sudden, severe deteriorationsudden, severe deterioration

• rule of thumb - Cr increasing > 1.0 mg/dL/dayrule of thumb - Cr increasing > 1.0 mg/dL/day

Acute tubular necrosis (ATN) - form of ARFAcute tubular necrosis (ATN) - form of ARF Oliguria: Oliguria: UOP less than 400 ml/dUOP less than 400 ml/d

• 500 mOsm daily solute concentrated to 1200 500 mOsm daily solute concentrated to 1200 mOsm/kgmOsm/kg

Anuria: Anuria: UOP less than 50 ml/dUOP less than 50 ml/d Nonoliguric renal failure Nonoliguric renal failure

progressive azotemia despite UOP > 400 ml/dprogressive azotemia despite UOP > 400 ml/d High-output renal failureHigh-output renal failure

acute renal insufficiency with UOP > 4 L/dacute renal insufficiency with UOP > 4 L/d

Acute Renal FailureAcute Renal Failure EtiologyEtiology

severe and prolonged hypotensionsevere and prolonged hypotension severe sepsis severe sepsis massive blood transfusionsmassive blood transfusions compartment syndromecompartment syndrome myoglobinuria/hemoglobinuriamyoglobinuria/hemoglobinuria radiocontrast radiocontrast aortic cross clamping aortic cross clamping (> 30 minutes)(> 30 minutes) drug-induceddrug-induced postinfectious glomerulonephritispostinfectious glomerulonephritis

Contributing factorsContributing factors ageage pre-existing renal vascular diseasepre-existing renal vascular disease pre-existing renal insufficiencypre-existing renal insufficiency

Myoglobinuria/Myoglobinuria/hemoglobinuriahemoglobinuria

Muscle necrosis or RBC destructionMuscle necrosis or RBC destruction HypotensionHypotension significant increase risk of ATN significant increase risk of ATN

can occur even if renal perfusion well maintainedcan occur even if renal perfusion well maintained Skeletal muscle Skeletal muscle (per kg of tissue)(per kg of tissue)

40-45 meg K 40-45 meg K 730 ml of H730 ml of H22OO 23 mmol of PO23 mmol of PO44

4 g myoglobin 4 g myoglobin ( takes 100-150 mg/dL to discolor urine)( takes 100-150 mg/dL to discolor urine) Severe crush injury/muscle ischemia causes Severe crush injury/muscle ischemia causes

hyperkalemia, hyperphosphotemia,azotemia, hyperkalemia, hyperphosphotemia,azotemia, hypocalemia, DIC, hypotension, and myoglobinuriahypocalemia, DIC, hypotension, and myoglobinuria

Predictors of ARF ?Predictors of ARF ?

Vivino G. Antonelli M. Moro ML. Cottini F. Conti G. Bufi Vivino G. Antonelli M. Moro ML. Cottini F. Conti G. Bufi M. Cannata F. Gasparetto A. Risk factors for M. Cannata F. Gasparetto A. Risk factors for acuteacute renal renal failure in trauma patients.failure in trauma patients. Intensive Care Medicine. Intensive Care Medicine. 24(8):808-14, 1998 Aug24(8):808-14, 1998 Aug

prospective, consecutive 153 trauma patientsprospective, consecutive 153 trauma patients

CPK > 10,000CPK > 10,000, PEEP > 6, hemoperitoneum, PEEP > 6, hemoperitoneum

Loun B. Astles R. Copeland KR. Sedor FA. Adaptation of a Loun B. Astles R. Copeland KR. Sedor FA. Adaptation of a quantitative immunoassay for urine myoglobin. Predictor quantitative immunoassay for urine myoglobin. Predictor in detecting in detecting renalrenal dysfunction. dysfunction. American Journal of American Journal of Clinical Pathology. 105(4):479-86, 1996 Apr.Clinical Pathology. 105(4):479-86, 1996 Apr.

urine assay for myoglobinuriaurine assay for myoglobinuria levels > 20,000 mcg/Llevels > 20,000 mcg/L

Key Management IssueKey Management Issue

Administer IV Fluid Administer IV Fluid Resuscitation Resuscitation

and and

Maintain UOP > 100 cc/hrMaintain UOP > 100 cc/hr

RhabdomyolysisRhabdomyolysis TreatmentTreatment

volume, volume, volumevolume, volume, volume!!!!!!• shock and rhabdomyolysis = renal failureshock and rhabdomyolysis = renal failure

maintain UOP > 100 - 200 cc/hrmaintain UOP > 100 - 200 cc/hr ? role or sodium bicarbonate? role or sodium bicarbonate

• precipitation of myoglobin urine pH < 5.6precipitation of myoglobin urine pH < 5.6• check urine pHcheck urine pH• consider if UOP marginal or severe hyperkalemiaconsider if UOP marginal or severe hyperkalemia

mannitol mannitol (avoid lasix if possible)(avoid lasix if possible)• volume expander, mild diuretic, free radical scavengervolume expander, mild diuretic, free radical scavenger

follow CPK levels follow CPK levels (most sensitive)(most sensitive)

Drug-Induced ARFDrug-Induced ARF

Pathogenesis depends on drugPathogenesis depends on drug Predisposing factorsPredisposing factors

volume depletion volume depletion ageage pre-existing renal diseasepre-existing renal disease prolonged therapyprolonged therapy other nephrotoxic agentsother nephrotoxic agents

Drug-Induced ARFDrug-Induced ARF AntibioticsAntibiotics

aminoglycosides aminoglycosides (most publicized)(most publicized)• however use of cephalosporins and clindamycin potentate however use of cephalosporins and clindamycin potentate

nephrotoxicitynephrotoxicity amphotericin B amphotericin B vancomycinvancomycin PCN can cause hypersensitivity nephritisPCN can cause hypersensitivity nephritis

Limit nephrotoxicityLimit nephrotoxicity low troughlow trough ? once a day dosing ? once a day dosing (proven to limit ototoxicity)(proven to limit ototoxicity) avoid NSAIDSavoid NSAIDS avoid combination of nephrotoxic antibioticsavoid combination of nephrotoxic antibiotics avoid hypotensionavoid hypotension

Radiocontrast-Induced Radiocontrast-Induced NephropathyNephropathy

Incidence as high as 13%Incidence as high as 13% MechanismsMechanisms

direct toxicitydirect toxicity renal ischemia renal ischemia (vasoconstriction)(vasoconstriction) intratubular obstructionintratubular obstruction immunologic abnormalityimmunologic abnormality

ClinicalClinical serum Cr elevation within 24 hoursserum Cr elevation within 24 hours serum Cr peak day 3-5serum Cr peak day 3-5 renal function normally returns by 10 daysrenal function normally returns by 10 days hemodialysis seldom neededhemodialysis seldom needed

Key Management IssueKey Management Issue

Administer IV Fluid Administer IV Fluid ResuscitationResuscitation

Only IV fluid hydration has been shown to reduce incidence of IV contrast nephropathy (not lasix or dopamine).

Should maintain UOP 12 hours before and 24 hours post procedure

Classification of ARFClassification of ARF Prerenal azotemiaPrerenal azotemia

inadequate renal perfusioninadequate renal perfusion characterized by low urine Na/high urine Crcharacterized by low urine Na/high urine Cr

Postrenal azotemiaPostrenal azotemia complete obstruction bilateral ureteral or lower complete obstruction bilateral ureteral or lower

urinary tacturinary tact

Acute tubular interstitial nephritisAcute tubular interstitial nephritis usual drug-inducedusual drug-induced signs of hypersensitivity signs of hypersensitivity (check urine eosinophils)(check urine eosinophils) renal biopsyrenal biopsy

ARF - Clinical ChangesARF - Clinical Changes

Increase serum Cr Increase serum Cr (> 1 to 1.5 mg/dL/d)(> 1 to 1.5 mg/dL/d) directly related to decreased GFRdirectly related to decreased GFR

Increase BUN Increase BUN (exceeds > 25 mg/dL/d)(exceeds > 25 mg/dL/d) related to decreased GFR and reabsorption related to decreased GFR and reabsorption

HyponatremiaHyponatremia intake fluids > UOP intake fluids > UOP (particularly hypotonic (particularly hypotonic

solutions)solutions) increased endogenous waterincreased endogenous water increased loss of urine sodiumincreased loss of urine sodium

ARF - Clinical ChangesARF - Clinical Changes

HyperkalemiaHyperkalemia reduced excretion from decreased GFR reduced excretion from decreased GFR impaired renal tubules secretionimpaired renal tubules secretion faster if muscle protein breakdown due to ischemia faster if muscle protein breakdown due to ischemia

or injuryor injury Metabolic acidosisMetabolic acidosis

accelerated protein catabolismaccelerated protein catabolism decreased excretion of acid loaddecreased excretion of acid load

Other electrolytesOther electrolytes hyperPOhyperPO44, hyperMg, hyperMg hypoCahypoCa

Differential DiagnosisDifferential Diagnosis

Postrenal azotemiaPostrenal azotemia rule out urinary tract obstructionrule out urinary tract obstruction

Prerenal azotemiaPrerenal azotemia hypovolemiahypovolemia cardiac failurecardiac failure

HypovolemiaHypovolemia Renal response to decreased blood flowRenal response to decreased blood flow

normal - conserve Hnormal - conserve H220 and Na0 and Na ARF - impaired ability to ARF - impaired ability to

concentrate/conserveconcentrate/conserve Differentiation of Pre-renal vs ARFDifferentiation of Pre-renal vs ARF

renal failure indexrenal failure index

fractional excretion of sodiumfractional excretion of sodium

RFI = Urine Cr / Plasma Cr < 1.0 prerenal azotemia

FE = (U Na/P Na) / (U Cr/P Cr) x 100 < 1.0 prerenal azotemia

SIMULATANEOUS SPOT PLASMA & URINE SAMPLES

UrinalysisUrinalysis

Prerenal azotemiaPrerenal azotemia unremarkableunremarkable

Obstructive uropathyObstructive uropathy unremarkableunremarkable

Glomerular diseaseGlomerular disease heavy proteinuriaheavy proteinuria sterile pyuria sterile pyuria mild microhematuriamild microhematuria casts (granular/WBC)casts (granular/WBC) ? eosinophils? eosinophils

Key Management IssueKey Management Issue

Fluid Challenge !!!!!Fluid Challenge !!!!!

RULE OUT HYPOVOLEMIA

1. test response to fluid challenge at least 500 to 1,000 cc (15-30 minutes)

2. consider CVP or pulmonary artery monitoring

Treatment of ARFTreatment of ARF DiureticsDiuretics

after hypovolemia ruled outafter hypovolemia ruled out if given soon after onset of oliguria may convert to if given soon after onset of oliguria may convert to

non-oliguric renal dysfunction non-oliguric renal dysfunction (better prognosis)(better prognosis) typestypes

• mannitolmannitol osmotic diuretic decrease proximal Na reabsorptionosmotic diuretic decrease proximal Na reabsorption dose: 25 g IV bolusdose: 25 g IV bolus

• lasixlasix inhibits active Na transport in loop of Henleinhibits active Na transport in loop of Henle dose: 20-40 mg IV initial, then double every 30 minutes if no dose: 20-40 mg IV initial, then double every 30 minutes if no

response (max dose 500 mg)response (max dose 500 mg)

• dopamine dopamine (low dose, 1-3 ug/kg/min)(low dose, 1-3 ug/kg/min) effects partially due to inhibition of ADHeffects partially due to inhibition of ADH

Sodium and Water BalanceSodium and Water Balance

Fluid restriction is important treatment of Fluid restriction is important treatment of ARFARF careful to maintain perfusioncareful to maintain perfusion problem sometimes with initial hemodialysisproblem sometimes with initial hemodialysis

Fluid requirementsFluid requirements GI and renal loss plus 500 ccGI and renal loss plus 500 cc accurate daily weights and I/O’saccurate daily weights and I/O’s

Metabolic AcidosisMetabolic Acidosis

Hypercatabolic generation of acid loadsHypercatabolic generation of acid loads Produces anion gapProduces anion gap Best treated with reducing catabolism Best treated with reducing catabolism

or hemodialysis, not sodium bicarbonateor hemodialysis, not sodium bicarbonate

HemodialysisHemodialysis

IndicationsIndications refractory pulmonary edemarefractory pulmonary edema hyperkalemic crisishyperkalemic crisis uremic complicationsuremic complications severe metabolic acidosissevere metabolic acidosis

A

E

I

O

U

Y

Acidosis

Electrolyte disturbance

Intoxication

Overload

Uremia

Why not

HemodialysisHemodialysis UltrafiltrationUltrafiltration

indicated in hemodynamically unstable patientsindicated in hemodynamically unstable patients continuous venovenous (CVVH) or arteriovenous (CAVH)continuous venovenous (CVVH) or arteriovenous (CAVH) filtrate removal of 500-800 ml/hrfiltrate removal of 500-800 ml/hr require often some heparinizationrequire often some heparinization

HemodialysisHemodialysis rapid correction of uremia, fluid overload, electrolyte rapid correction of uremia, fluid overload, electrolyte

disturbances, and acidosisdisturbances, and acidosis ““prophylactic” dialysis probably beneficialprophylactic” dialysis probably beneficial added benefit by providing for adequate calories and added benefit by providing for adequate calories and

proteinprotein

ARF - Special ARF - Special Consideration/ComplicationConsideration/Complication

Adjustment of medicationsAdjustment of medications

CoagulopathyCoagulopathy platelet dysfunction in aggregationplatelet dysfunction in aggregation

• treatment with DDAVP (0.3 ug/kg)treatment with DDAVP (0.3 ug/kg) low antithrombin III levelslow antithrombin III levels

• microvascular thrombosismicrovascular thrombosis

HyperkalemiaHyperkalemia increased with blood transfusions, acidosis, and increased with blood transfusions, acidosis, and

hyperosmolemia hyperosmolemia (ie treatment with diuretics)(ie treatment with diuretics) usual treatment usual treatment (glucose + insulin, calcium IV)(glucose + insulin, calcium IV) avoid kayexelate avoid kayexelate (Na exchange for K)(Na exchange for K)

ARF - Special ARF - Special Consideration/ComplicationConsideration/Complication AnemiaAnemia

reduced EPO levelsreduced EPO levels contributing factors include GI blood loss and contributing factors include GI blood loss and

hemodialysis hemodialysis (i.e. hemolysis)(i.e. hemolysis) treatment with recombinant EPO/Fe treatment with recombinant EPO/Fe

replacementreplacement

Stress gastritisStress gastritis more than 20% of ARF patientsmore than 20% of ARF patients treatmenttreatment

• AlOH antacids AlOH antacids (also treats hyperphosphotemia)(also treats hyperphosphotemia)• H2 blockersH2 blockers

ARF - Special ARF - Special Consideration/ComplicationConsideration/Complication

Pericarditis Pericarditis (uremia)(uremia) with or without pleuritiswith or without pleuritis presence of chest pain or friction rubpresence of chest pain or friction rub some with fever with or without leukocytosissome with fever with or without leukocytosis treatment with hemodialysistreatment with hemodialysis

Nutritional supportNutritional support problemsproblems

• insulin resistanceinsulin resistance• negligible free water and urea clearancenegligible free water and urea clearance• ? high energy requirement? high energy requirement

ARF - Special ARF - Special Consideration/ComplicationConsideration/Complication Nutritional supportNutritional support

treatmenttreatment• minimize free waterminimize free water• do not restrict protein if needed unless unable to do not restrict protein if needed unless unable to

clear with hemodialysisclear with hemodialysis

Outcomes of ARFOutcomes of ARF Oliguric ARFOliguric ARF

expect return of renal function in 3 weeksexpect return of renal function in 3 weeks if enter diuretic phase, likelihood of survival greatly if enter diuretic phase, likelihood of survival greatly

increasedincreased older patients progress to chronic renal failure much older patients progress to chronic renal failure much

more oftenmore often

Non-oliguric ARFNon-oliguric ARF increasing secondary earlier and aggressive fluid increasing secondary earlier and aggressive fluid

resuscitation and conversion with diureticsresuscitation and conversion with diuretics easier to manage than oliguriceasier to manage than oliguric only few require dialysisonly few require dialysis much lower mortalitymuch lower mortality

Questions ?Questions ?