October 1, 2012 Volume 86, Number 7www.aafp.org/afpAmerican Family Physician631Acute Kidney Injury: A Guide to Diagnosis and ManagementMAHBOOB RAHMAN, MD, MS, Case Western Reserve University School of Medicine, Cleveland, OhioFARIHA SHAD, MD, Kaiser Permanente, Cleveland, Ohio MICHAEL C. SMITH, MD, Case Western Reserve University School of Medicine, Cleveland, OhioThe incidence of acute kidney injury has increased in recent years, both inthecommunityandinhospi-talsettings.1,2Theestimatedinci-dence of acute kidney injury is two to three casesper1,000persons.3Sevenpercentof hospitalizedpatientsandabouttwo-thirds ofpatientsinintensivecareunitsdevelop acutekidneyinjury,2oftenaspartofthe multiple organ dysfunction syndrome.4 Acutekidneyinjuryisassociatedwith ahighrateofadverseoutcomes;mortal-ityratesrangebetween25and80percent, depending on the cause and the clinical sta-tus of the patient.5-7 These data highlight the importanceofrecognitionandappropriate management,usuallyincollaborationwith nephrologists and other subspecialists.DenitionAcutekidneyinjuryisdenedasanabrupt (within 48 hours) reduction in kidney func-tionbasedonanelevationinserumcreati-ninelevel,areductioninurineoutput,the needforrenalreplacementtherapy(dialy-sis),oracombinationofthesefactors.Itis classied in three stages (Table 1).8 The term acutekidneyinjuryshouldreplaceterms suchasacuterenalfailureandacuterenal insufciency,whichpreviouslyhavebeen used to describe the same clinical condition.EtiologyThecausesofacutekidneyinjurycanbe dividedintothreecategories(Table2 9): prerenal(causedbydecreasedrenalperfu-sion,oftenbecauseofvolumedepletion), Acute kidney injury is characterized by abrupt deterioration in kidney function, manifested by an increase in serum creatinine level with or without reduced urine output. The spectrum of injury ranges from mild to advanced, some-times requiring renal replacement therapy. The diagnostic evaluation can be used to classify acute kidney injury as prerenal, intrinsic renal, or postrenal. The initial workup includes a patient history to identify the use of nephrotoxic medicationsorsystemicillnessesthatmightcausepoorrenalperfusionordirectlyimpairrenalfunction.Physi-calexaminationshouldassessintravascularvolumestatusandidentifyskinrashesindicativeofsystemicillness. The initial laboratory evaluation should include measurement of serum creatinine level, complete blood count, uri-nalysis, and fractional excretion of sodium. Ultrasonography of the kidneys should be performed in most patients, particularly in older men,toruleoutobstruction.Managementofacutekidneyinjury involvesuidresuscitation,avoidanceofnephrotoxicmedications andcontrastmediaexposure,andcorrectionofelectrolyteimbal-ances.Renalreplacementtherapy(dialysis)isindicatedforrefrac-toryhyperkalemia;volumeoverload;intractableacidosis;uremic encephalopathy,pericarditis,orpleuritis;andremovalofcertain toxins.Recognitionofriskfactors(e.g.,olderage,sepsis,hypovo-lemia/shock,cardiacsurgery,infusionofcontrastagents,diabetes mellitus,preexistingchronickidneydisease,cardiacfailure,liver failure)isimportant.Team-basedapproachesforprevention,early diagnosis,andaggressivemanagementarecriticalforimproving outcomes.(AmFamPhysician.2012;86(7):631-639.Copyright 2012 American Academy of Family Physicians.) ILLUSTRATION BY CHRISTY KRAMESDownloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright 2012 American Academy of Family Physicians. For the private, noncom-mercial use of one individual user of the Web site. All other rights reserved. Contact copyrights@aafp.org for copyright questions and/or permission requests.Acute Kidney Injury632American Family Physicianwww.aafp.org/afpVolume 86, Number 7 October 1, 2012intrinsic renal (caused by a process within the kidneys), andpostrenal(causedbyinadequatedrainageofurine distaltothekidneys).Inpatientswhoalreadyhave underlying chronic kidney disease, any of these factors, but especially volume depletion, may cause acute kidney injuryinadditiontothechronicimpairmentofrenal function.PRERENAL CAUSESApproximately 70 percent of community-acquired cases of acute kidney injury are attributed to prerenal causes.10 In these cases, underlying kidney function may be nor-mal,butdecreasedrenalperfusionassociatedwith intravascularvolumedepletion(e.g.,fromvomitingor diarrhea) or decreased arterial pressure (e.g., from heart failureorsepsis)resultsinareducedglomerularltra-tionrate.Autoregulatorymechanismsoftencancom-pensateforsomedegreeofreducedrenalperfusionin anattempttomaintaintheglomerularltrationrate. Inpatientswithpreexistingchronickidneydisease, however,thesemechanismsareimpaired,andthesus-ceptibilitytodevelopacute-on-chronicrenalfailureis higher.11Severalmedicationscancauseprerenalacutekidney injury.Notably,angiotensin-convertingenzymeinhibi-tors and angiotensin receptor blockers can impair renal perfusionbycausingdilationoftheefferentarteriole and reduce intraglomerular pressure. Nonsteroidal anti-inammatorydrugsalsocandecreasetheglomerular ltrationratebychangingthebalanceofvasodilatory/vasoconstrictiveagentsintherenalmicrocirculation. Thesedrugsandotherslimitthenormalhomeostatic responsestovolumedepletionandcanbeassociated withadeclineinrenalfunction.Inpatientswithpre-renalacutekidneyinjury,kidneyfunctiontypically returns to baseline after adequate volume status is estab-lished, the underlying cause is treated, or the offending drug is discontinued.Table 1. Stages of Acute Kidney InjuryThe rights holder did not grant the American Academy of Family Physicians the right to sublicense this material to a third party. For the missing item, see the original print version of this publication.SORT: KEY RECOMMENDATIONS FOR PRACTICEClinical recommendationEvidencerating ReferencesThe diagnosis of acute kidney injury is based on serum creatinine levels, urine output, and the need for renal replacement therapy.C 8Renal ultrasonography should be performed in most patients with acute kidney injury to rule out obstruction. C 17Adequate uid balance should be maintained in patients with acute kidney injury by using isotonic solutions (e.g., normal saline) instead of hyperoncotic solutions (e.g., dextrans, hydroxyethyl starch, albumin).C 19Dopamine use is not recommended for the prevention of acute kidney injury. A 21Diuretics do not improve morbidity, mortality, or renal outcomes, and should not be used to prevent or treat acute kidney injury in the absence of volume overload.A 22Consider therapy with immunosuppressive agents (e.g., cyclophosphamide, prednisone) in patients with rapidly progressive glomerulonephritis. C 23A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.Acute Kidney InjuryOctober 1, 2012 Volume 86, Number 7www.aafp.org/afpAmerican Family Physician633INTRINSIC RENAL CAUSESIntrinsic renal causes are also important sources of acute kidney injury and can be categorized by the component of the kidney that is primarily affected (i.e., tubular, glo-merular, interstitial, or vascular).Acutetubularnecrosisisthemostcommontypeof intrinsicacutekidneyinjuryinhospitalizedpatients. The cause is usually ischemic (from prolonged hypoten-sion)ornephrotoxic(fromanagentthatistoxictothe tubularcells).Incontrasttoaprerenaletiology,acute kidney injury caused by acute tubular necrosis does not improvewithadequaterepletionofintravascularvol-umeandbloodowtothekidneys.Bothischemicand nephrotoxic acute tubular necrosis can resolve over time, althoughtemporaryrenalreplacementtherapymaybe required,dependingonthedegreeofrenalinjuryand the presence of preexisting chronic kidney disease.Glomerularcausesofacutekidneyinjuryarethe result of acute inammation of blood vessels and glom-eruli.Glomerulonephritisisusuallyamanifestation ofasystemicillness(e.g.,systemiclupuserythemato-sus)orpulmonaryrenalsyndromes(e.g.,Goodpasture syndrome,Wegenergranulomatosis).History,physical examination,andurinalysisarecrucialfordiagnosing glomerulonephritis(Table3 9 andFigure112).Because managementofteninvolvesadministrationofimmu-nosuppressive or cytotoxic medications with potentially severeadverseeffects,renalbiopsyisoftenrequiredto conrm the diagnosis before initiating therapy. Acute interstitial nephritis can be secondary to many conditions,butmostcasesarerelatedtomedication use,makingpatienthistorythekeytodiagnosis.In aboutone-thirdofcases,thereisahistoryofmacu-lopapularerythematousrash,fever,arthralgias,ora combination of these symptoms.13 Eosinophiluria may befoundinpatientswithacuteinterstitialnephritis, butitisnotpathognomonicofthisdisease.Akidney biopsymaybeneededtodistinguishbetweenallergic interstitialnephritisandotherrenalcausesofacute kidneyinjury.Inadditiontodiscontinuingoffending agents,steroidsmaybebenecialifgivenearlyinthe course of disease.14Acute events involving renal arteries or veins can also leadtointrinsicacutekidneyinjury.Renalatheroem-bolic disease is the most common cause and is suspected with a recent history of arterial catheterization, the pres-enceofaconditionrequiringanticoagulation,orafter vascular surgery. Physical examination and history pro-vide important clues to the diagnosis (Table 3 9). Vascular causes of acute kidney injury usually require imaging to conrm the diagnosis.Table 2. Causes of Acute Kidney InjuryThe rights holder did not grant the American Acad-emy of Family Physicians the right to sublicense this materialtoathirdparty.Forthemissingitem,see the original print version of this publication.Acute Kidney Injury634American Family Physicianwww.aafp.org/afpVolume 86, Number 7 October 1, 2012POSTRENAL CAUSESPostrenal causes typically result from obstruction of uri-naryow,andprostatichypertrophyisthemostcom-mon cause of obstruction in older men. Prompt diagnosis followed by early relief of obstruction is associated with improvement in renal function in most patients.Clinical PresentationClinicalpresentationvarieswiththecauseandsever-ityofrenalinjury,andassociateddiseases.Mostpatients withmildtomoderateacutekidneyinjuryareasymp-tomaticandareidentiedonlaboratorytesting.Patients with severe cases, however, may be symptomatic and pres-ent with listlessness, confusion, fatigue, anorexia, nausea, vomiting, weight gain, or edema.15 Patients can also pres-ent with oliguria (urine output less than 400 mL per day), anuria (urine output less than 100 mL per day), or normal volumes of urine (nonoliguric acute kidney injury). Other presentations of acute kidney injury may include develop-mentofuremicencephalopathy(manifestedbyadecline in mental status, asterixis, or other neurologic symptoms), anemia, or bleeding caused by uremic platelet dysfunction.DiagnosisApatienthistoryandphysicalexamination,withan emphasisonassessingthepatientsvolumestatus,are crucialfordeterminingthecauseofacutekidneyinjury (Table 3 9). The history should identify use of nephrotoxic medicationsorsystemicillnessesthatmightcausepoor renalperfusionordirectlyimpairrenalfunction.Physi-cal examination should assess intravascular volume status and any skin rashes indicative of systemic illness. The ini-tial laboratory evaluation should include urinalysis, com-plete blood count, and measurement of serum creatinine levelandfractionalexcretionofsodium(FENa).Imaging studiescanhelpruleoutobstruction.Usefultestsare summarized in Table 4.16 Figure 1 presents an overview of the diagnosis and management of acute kidney injury.12SERUM CREATININE LEVELIt is important to compare the patients current serum cre-atinine level with previous levels to determine the duration andacuityofthedisease.Thedenitionofacutekidney injury indicates that a rise in creatinine has occurred within 48 hours, although in the outpatient setting, it may be hard Table 3. History and Physical Examination Findings for Categorizing Acute Kidney InjuryThe rights holder did not grant the American Academy of Family Physicians the right to sublicense this material to a third party. For the missing item, see the original print version of this publication.Acute Kidney InjuryDiagnosis and Treatment of Acute Kidney InjuryThe rights holder did not grant the American Academy of Family Physicians the right to sublicense this material to a third party. For the missing item, see the original print version of this publication.Figure 1. Algorithm for the diagnosis and treatment of acute kidney injury.AdaptedwithpermissionfromSmithMC.Acuterenalfailure.In:ResnickMI,ElderJS,SpirnakJP,eds.ClinicalDecisionsinUrology.3rded.Hamilton, Ontario, Canada: BC Decker, Inc.; 2004:61.Acute Kidney Injury636American Family Physicianwww.aafp.org/afpVolume 86, Number 7 October 1, 2012to ascertain when the rise actually happened. A high serum creatinine level in a patient with a previously normal docu-mented level suggests an acute process, whereas a rise over weeks to months represents a subacute or chronic process. URINALYSISUrinalysisisthemostimportantnoninvasivetestin theinitialworkupofacutekidneyinjury.Findingson urinalysis guide the differential diagnosis and direct fur-ther workup (Figure 112).COMPLETE BLOOD COUNTThe presence of acute hemolytic anemia with the periph-eral smear showing schistocytes in the setting of acute kid-ney injury should raise the possibility of hemolytic uremic syndrome or thrombotic thrombocytopenic purpura.Table 4. Diagnostic Test Results and Corresponding Diseases in Patients with Acute Kidney InjuryThe rights holder did not grant the American Academy of Family Physicians the right to sublicense this material to a third party. For the missing item, see the original print version of this publication.Acute Kidney InjuryOctober 1, 2012 Volume 86, Number 7www.aafp.org/afpAmerican Family Physician637URINE ELECTROLYTESInpatientswitholiguria,measurementofFENaishelp-ful in distinguishing prerenal from intrinsic renal causes ofacutekidneyinjury.FENaisdenedbythefollowing formula:FENa = 100 (urinary sodium serum creatinine)(serum sodium urinary creatinine)Onlinecalculatorsarealsoavailable.Avaluelessthan 1percentindicatesaprerenalcauseofacutekidney injury,whereasavaluegreaterthan2percentindicates anintrinsicrenalcause.Inpatientsondiuretictherapy, however,aFENahigherthan1percentmaybecaused bynatriuresisinducedbythediuretic,andisalessreli-able measure of a prerenal state. In such cases, fractional excretionofureamaybehelpful,withvalueslessthan 35percentindicatingaprerenalcause.FENavaluesless than 1 percent are not specic for prerenal causes of acute kidney injury because these values can occur in other con-ditions,suchascontrastnephropathy,rhabdomyolysis, acute glomerulonephritis, and urinary tract obstruction.IMAGING STUDIESRenalultrasonographyshouldbeperformedinmost patientswithacutekidneyinjury,particularlyinolder men,toruleoutobstruction(i.e.,apostrenalcause).17,18 Thepresenceofpostvoidresidualurinegreaterthan 100mL(determinedbyabladderscanorviaurethral catheterizationifbladderscanisunavailable)suggests postrenalacutekidneyinjuryandrequiresrenalultra-sonographytodetecthydronephrosisoroutletobstruc-tion.Todiagnoseextrarenalcausesofobstruction(e.g., pelvictumors),otherimagingmodalities,suchascom-puted tomography or magnetic resonance imaging, may be required.RENAL BIOPSYRenalbiopsyisreservedforpatientsinwhompre-renalandpostrenalcausesofacutekidneyinjuryhave beenexcludedandthecauseofintrinsicrenalinjuryis unclear.Renalbiopsyisparticularlyimportantwhen clinical assessment and laboratory investigations suggest adiagnosisthatrequiresconrmationbeforedisease-specictherapy(e.g.,immunosuppressivemedications) isinstituted.Renalbiopsymayneedtobeperformed urgently in patients with oliguria who have rapidly wors-ening acute kidney injury, hematuria, and red blood cell casts. In this setting, in addition to indicating a diagno-sis that requires immunosuppressive therapy, the biopsy maysupporttheinitiationofspecialtherapies,suchas plasmapheresis if Goodpasture syndrome is present.ManagementOptimalmanagementofacutekidneyinjuryrequires closecollaborationamongprimarycarephysicians, nephrologists, hospitalists, and other subspecialists par-ticipatinginthecareofthepatient.Afteracutekidney injury is established, management is primarily supportive.Patientswithacutekidneyinjurygenerallyshould behospitalizedunlesstheconditionismildandclearly resultingfromaneasilyreversiblecause.Thekeyto managementisassuringadequaterenalperfusionby achievingandmaintaininghemodynamicstabilityand avoiding hypovolemia. In some patients, clinical assess-mentofintravascularvolumestatusandavoidanceof volumeoverloadmaybedifcult,inwhichcasemea-surement of central venous pressures in an intensive care setting may be helpful.Ifuidresuscitationisrequiredbecauseofintravas-cular volume depletion, isotonic solutions (e.g., normal saline)arepreferredoverhyperoncoticsolutions(e.g., dextrans, hydroxyethyl starch, albumin).19 A reasonable goal is a mean arterial pressure greater than 65 mm Hg, whichmayrequiretheuseofvasopressorsinpatients withpersistenthypotension.20Renal-dosedopamineis associatedwithpooreroutcomesinpatientswithacute kidneyinjury;itisnolongerrecommended.21Cardiac function can be optimized as needed with positive ino-tropes, or afterload and preload reduction.Attentiontoelectrolyteimbalances(e.g.,hyperkale-mia,hyperphosphatemia,hypermagnesemia,hypona-tremia, hypernatremia, metabolic acidosis) is important. Severehyperkalemiaisdenedaspotassiumlevelsof 6.5 mEq per L (6.5 mmol per L) or greater, or less than 6.5mEqperLwithelectrocardiographicchangestypi-cal of hyperkalemia (e.g., tall, peaked T waves). In severe hyperkalemia,5to10unitsofregularinsulinanddex-trose 50% given intravenously can shift potassium out of circulation and into the cells. Calcium gluconate (10 mL of 10% solution infused intravenously over ve minutes) isalsousedtostabilizethemembraneandreducethe risk of arrhythmias when there are electrocardiographic changesshowinghyperkalemia.Inpatientswithout electrocardiographic evidence of hyperkalemia, calcium gluconate is not necessary, but sodium polystyrene sulfo-nate (Kayexalate) can be given to lower potassium levels gradually,andloop diuretics can be used inpatientswhoare responsive to diuret-ics. Dietary intake of potassium should be restricted.Patients with acute kidney injury are more likely to develop chronic kidney disease in the future. Acute Kidney Injury638American Family Physicianwww.aafp.org/afpVolume 86, Number 7 October 1, 2012Themainindicationforuseofdiureticsismanage-ment of volume overload. Intravenous loop diuretics, as abolusorcontinuousinfusion,canbehelpfulforthis purpose. However, it is important to note that diuretics do not improve morbidity, mortality, or renal outcomes, and should not be used to prevent or treat acute kidney injury in the absence of volume overload.22All medications that may potentially affect renal func-tionbydirecttoxicityorbyhemodynamicmechanisms should be discontinued, if possible. For example, metfor-min(Glucophage)shouldnotbegiventopatientswith diabetesmellituswhodevelopacutekidneyinjury.The dosagesofessentialmedicationsshouldbeadjustedfor the lower level of kidney function. Avoidance of iodinated contrast media and gadolinium is important and, if imag-ing is needed, noncontrast studies are recommended.Supportive therapies (e.g., antibiotics, maintenance of adequate nutrition, mechanical ventilation, glycemic con-trol,anemiamanagement)shouldbepursuedbasedon standard management practices. In patients with rapidly progressive glomerulonephritis, treatment with pulse ste-roids, cytotoxic therapy, or a combination may be consid-ered, often after conrmation of the diagnosis by kidney biopsy.23Insomepatients,themetabolicconsequences ofacutekidneyinjurycannotbeadequatelycontrolled withconservativemanagement,andrenalreplacement therapy will be required. The indications for initiation of renalreplacementtherapyincluderefractoryhyperkale-mia, volume overload refractory to medical management, uremicpericarditisorpleuritis,uremicencephalopathy, intractable acidosis, and certain poisonings and intoxica-tions (e.g., ethylene glycol, lithium).24PrognosisPatientswithacutekidneyinjuryaremorelikelyto developchronickidneydiseaseinthefuture.Theyare also at higher risk of end-stage renal disease and prema-ture death.25-27 Patients who have an episode of acute kid-ney injury should be monitored for the development or worsening of chronic kidney disease.Table 5. Preventive Strategies for Patients at High Risk of Acute Kidney InjuryRisk factors Preventive strategiesCancer chemotherapy with risk of tumor lysis syndrome27Hydration and allopurinol (Zyloprim) administration a few days before chemotherapy initiation in patients at high risk of tumor lysis syndrome to prevent uric acid nephropathyExposure to nephrotoxic medicationsAvoid nephrotoxic medications if possibleMeasure and follow drug levels if availableUse appropriate dosing, intervals, and duration of therapyExposure to radiographic contrast agents29Avoid use of intravenous contrast media when risks outweigh benetsIf use of contrast media is essential, use iso-osmolar or low-osmolar contrast agent with lowest volume possibleOptimize volume status before administration of contrast media; use of isotonic normal saline or sodium bicarbonate may be considered in high-risk patients who are not at risk of volume overloadUse of N-acetylcysteine may be consideredHemodynamic instability Optimal uid resuscitation; although there is no consensus, a mean arterial pressure goal of > 65 mm Hg is widely used; isotonic solutions (e.g., normal saline) are preferred over hyperoncotic solutions (e.g., albumin)19Vasopressors are recommended for persistent hypotension (mean arterial pressure < 65 mm Hg) despite uid resuscitation; choice of vasoactive agent should be tailored to patients needs20 Dopamine is not recommended21Hepatic failure30Avoid hypotension and gastrointestinal bleedingEarly recognition and treatment of spontaneous bacterial peritonitis; use albumin, 1.5 g per kg at diagnosis and 1 g per kg at 48 hoursEarly recognition and management of ascitesAlbumin infusion during large volume paracentesisAvoid nephrotoxic medicationsRhabdomyolysis20Maintain adequate hydrationAlkalinization of the urine with intravenous sodium bicarbonate in select patients (normal calcium, bicarbonate less than 30 mEq per L [30 mmol per L], and arterial pH less than 7.5)Undergoing surgery Adequate volume resuscitation/prevention of hypotension, sepsis, optimizing cardiac functionConsider holding renin-angiotensin system antagonists preoperatively 31Information from references 19 through 21, 27, and 29 through 31.Acute Kidney InjuryOctober 1, 2012 Volume 86, Number 7www.aafp.org/afpAmerican Family Physician639PreventionBecauseofthemorbidityandmortalityassociatedwith acute kidney injury, it is important for primary care physi-cians to identify patients who are at high risk of developing this type of injury and to implement preventive strategies. Thoseathighestriskincludeadultsolderthan75years; personswithdiabetesorpreexistingchronickidneydis-ease; persons with medical problems such as cardiac fail-ure, liver failure, or sepsis; and those who are exposed to contrastagentsorwhoareundergoingcardiacsurgery.28 Preventivestrategiescanbetailoredtotheclinicalcir-cumstances of the individual patient (Table 5).19-21,27,29-31Data Sources: We searched PubMed (also with the Clinical Queries function), the Cochrane Database of Systematic Reviews, and the National Guidelines Clearinghouse using the key words AKI, acute kidney injury, and acute renal failure. Search date: February 2012.The AuthorsMAHBOOBRAHMAN,MD,MS,isanassociateprofessorofmedicineat Case Western Reserve University School of Medicine in Cleveland, Ohio, andastaffnephrologistatUniversityHospitalsCaseMedicalCenterin Cleveland and at Louis Stokes Cleveland VA Medical Center.FARIHA SHAD, MD, is a nephrologist at Kaiser Permanente in Cleveland. At the time the article was written, Dr. Shad was a fellow at Case Western Reserve University School of Medicine.MICHAELC.SMITH,MD,isaprofessorofmedicineatCaseWestern Reserve University School of Medicine, and a staff nephrologist at Univer-sity Hospitals Case Medical Center. Address correspondence to Mahboob Rahman, MD, MS, Case Western ReserveUniversity,11100EuclidAve.,Cleveland,OH44106.Reprints are not available from the authors.Author disclosure: No relevant nancial afliations to disclose.REFERENCES1.Hsu CY, McCulloch CE, Fan D, Ordoez JD, Chertow GM, Go AS. Com-munity-basedincidenceofacuterenalfailure.KidneyInt.2007;72(2): 208-212. 2.NashK,HafeezA,HouS.Hospital-acquiredrenalinsufciency.AmJ Kidney Dis. 2002;39(5):930-936. 3.Hoste EA, Schurgers M. Epidemiology of acute kidney injury: how big is the problem? Crit Care Med. 2008;36(4 suppl):S146-S151. 4.Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injuryareassociatedwithhospitalmortalityincriticallyillpatients:a cohort analysis. Crit Care. 2006;10(3):R73. 5.Ympa YP, Sakr Y, Reinhart K, Vincent JL. Has mortality from acute renal failuredecreased?Asystematicreviewoftheliterature.AmJMed. 2005;118(8):827-832. 6.Gruberg L, Weissman NJ, Pichard AD, et al. Impact of renal function on morbidityandmortalityafterpercutaneousaortocoronarysaphenous vein graft intervention. Am Heart J. 2003;145(3):529-534. 7.Uchino S, Kellum JA, Bellomo R, et al.; Beginning and Ending Supportive TherapyfortheKidney(BESTKidney)Investigators.Acuterenalfail-ureincriticallyillpatients:amultinational,multicenterstudy.JAMA. 2005;294(7):813-818. 8.MehtaRL,KellumJA,ShahSV,etal.AcuteKidneyInjuryNetwork: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. 9.HolleyJL.Clinicalapproachtothediagnosisofacuterenalfailure.In: Greenberg A, Cheung AK, eds. Primer on Kidney Diseases. 5th ed. Phil-adelphia, Pa.: National Kidney Foundation; 2009. 10. KaufmanJ,DhakalM,PatelB,HamburgerR.Community-acquired acute renal failure. Am J Kidney Dis. 1991;17(2):191-198. 11.ChristensenPK,HansenHP,ParvingHH.Impairedautoregulationof GFRinhypertensivenon-insulindependentdiabeticpatients.Kidney Int. 1997;52(5):1369-1374. 12.Smith MC. Acute renal failure. In: Resnick MI, Elder JS, Spirnak JP, eds. ClinicalDecisionsinUrology.3rded.Hamilton,Ontario,Canada:BC Decker, Inc.; 2004:60-63. 13.ClarksonMR,GiblinL,OConnellFP,etal.Acuteinterstitialnephritis: clinicalfeaturesandresponsetocorticosteroidtherapy.NephrolDial Transplant. 2004;19(11):2778-2783. 14. Gonzlez E, Gutirrez E, Galeano C, et al.; Grupo Madrileo De Nefri-tis Intersticiales. Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis. Kid-ney Int. 2008;73(8):940-946. 15. Meyer TW, Hostetter TH. Uremia. N Engl J Med. 2007;357(13):1316-1325. 16. Agrawal M, Swartz R. Acute renal failure [published correction appears in Am Fam Physician. 2001;63(3):445]. Am Fam Physician. 2000;61(7): 2077-2088. 17.LewingtonA,KanagasundaramS.Clinicalpracticeguidelines:acute kidneyinjury.2011.http://www.renal.org/clinical /guidelinessection/AcuteKidneyInjury.aspx. Accessed September 7, 2012. 18. ONeillWC.Sonographicevaluationofrenalfailure.AmJKidneyDis. 2000;35(6):1021-1038. 19.Schortgen F, Lacherade JC, Bruneel F, et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet. 2001;357(9260):911-916. 20. BrochardL,AbrougF,BrennerM,etal.AnOfcialATS/ERS/ESICM/SCCM/SRLFStatement:PreventionandManagementofAcuteRenal Failure in the ICU Patient: an international consensus conference in inten-sive care medicine. Am J Respir Crit Care Med. 2010;181(10):1128-1155. 21.FriedrichJO,AdhikariN,HerridgeMS,BeyeneJ.Meta-analysis:low-dose dopamine increases urine output but does not prevent renal dys-function or death. Ann Intern Med. 2005;142(7):510-524. 22. HoKM,SheridanDJ.Meta-analysisoffrusemidetopreventortreat acute renal failure. BMJ. 2006;333(7565):420. 23. Walters G, Willis NS, Craig JC. Interventions for renal vasculitis in adults. Cochrane Database Syst Rev. 2008;(3):CD003232. 24. Mehta RL. Indications for dialysis in the ICU: renal replacement vs. renal support. Blood Purif. 2001;19(2):227-232. 25. Goldberg R, Dennen P. Long-term outcomes of acute kidney injury. Adv Chronic Kidney Dis. 2008;15(3):297-307. 26. Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a sys-tematic review and meta-analysis. Am J Kidney Dis. 2009;53(6):961-973. 27.Pession A, Masetti R, Gaidano G, et al. Risk evaluation, prophylaxis, and treatment of tumor lysis syndrome: consensus of an Italian expert panel. Adv Ther. 2011;28(8):684-697. 28. Leblanc M, Kellum JA, Gibney RT, Lieberthal W, Tumlin J, Mehta R. Risk factors for acute renal failure: inherent and modiable risks. Curr Opin Crit Care. 2005;11(6):533-536. 29. RundbackJH,NahlD,YooV.Contrast-inducednephropathy.JVasc Surg. 2011;54(2):575-579. 30. Nadim MK, Kellum JA, Davenport A, et al. Hepatorenal syndrome: the 8th international consensus conference of the Acute Dialysis Quality Ini-tiative (ADQI) group. Crit Care. 2012;16(1):R23. 31.AuronM,HarteB,KumarA,MichotaF.Renin-angiotensinsystem antagonists in the perioperative setting: clinical consequences and rec-ommendations for practice. Postgrad Med J. 2011;87(1029):472-481.