OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY KDIGO Clinical Practice Guideline for Acute Kidney Injury VOLUME 2 | ISSUE 1 | MARCH 2012 http://www.kidney-international.org KKII__SSuuppppCCoovveerr__22..11..iinndddd 11 22//77//1122 1122::3322 PPMM http://www.kidney-international.org contents &2012KDIGO VOL 2|SUPPLEMENT 1|MARCH 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury iv TablesandFigures 1 Notice 2 WorkGroupMembership 3 KDIGOBoardMembers 4 ReferenceKeys 5 AbbreviationsandAcronyms 6 Abstract 7 Foreword 8 SummaryofRecommendationStatements 13 Section1: IntroductionandMethodology 13 Chapter1.1: Introduction 17 Chapter1.2: Methodology 19 Section2: AKIDefinition 19 Chapter2.1: DefinitionandclassificationofAKI 23 Chapter2.2: Riskassessment 25 Chapter2.3: EvaluationandgeneralmanagementofpatientswithandatriskforAKI 28 Chapter2.4: Clinicalapplications 33 Chapter2.5: Diagnosticapproachtoalterationsinkidneyfunctionandstructure 37 Section3: PreventionandTreatmentofAKI 37 Chapter3.1: HemodynamicmonitoringandsupportforpreventionandmanagementofAKI 42 Chapter 3.2: General supportive management of patients with AKI, including management of complications 43 Chapter3.3: Glycemiccontrolandnutritionalsupport 47 Chapter3.4: TheuseofdiureticsinAKI 50 Chapter3.5: Vasodilatortherapy:dopamine,fenoldopam,andnatriureticpeptides 57 Chapter3.6: Growthfactorintervention 59 Chapter3.7: Adenosinereceptorantagonists 61 Chapter3.8: Preventionofaminoglycoside-andamphotericin-relatedAKI 66 Chapter3.9: OthermethodsofpreventionofAKIinthecriticallyill 69 Section4: Contrast-inducedAKI 69 Chapter4.1: Contrast-inducedAKI:definition,epidemiology,andprognosis 72 Chapter4.2: AssessmentofthepopulationatriskforCI-AKI 76 Chapter4.3: NonpharmacologicalpreventionstrategiesofCI-AKI 80 Chapter4.4: PharmacologicalpreventionstrategiesofCI-AKI 87 Chapter4.5: Effectsofhemodialysisorhemofiltration 89 Section5: DialysisInterventionsforTreatmentofAKI 89 Chapter5.1: TimingofrenalreplacementtherapyinAKI 93 Chapter5.2: CriteriaforstoppingrenalreplacementtherapyinAKI 95 Chapter5.3: Anticoagulation 101 Chapter5.4: VascularaccessforrenalreplacementtherapyinAKI 105 Chapter5.5: DialyzermembranesforrenalreplacementtherapyinAKI 107 Chapter5.6: ModalityofrenalreplacementtherapyforpatientswithAKI 111 Chapter5.7: BuffersolutionsforrenalreplacementtherapyinpatientswithAKI 113 Chapter5.8: DoseofrenalreplacementtherapyinAKI 116 BiographicandDisclosureInformation 122 Acknowledgments 124 References contents http://www.kidney-international.org &2012KDIGO TABLES 18 Table 1. Implications ofthestrength ofa recommendation 19 Table 2. Staging ofAKI 21 Table 3. Comparison ofRIFLE and AKIN criteria fordiagnosis and classification ofAKI 21 Table 4. Cross-tabulation ofpatientsclassified byRIFLE vs. AKIN 22 Table 5. Causes ofAKI and diagnostictests 23 Table 6. Causes ofAKI:exposuresand susceptibilities fornon-specific AKI 28 Table 7. AKI diagnosis 29 Table 8. Overview of the approaches to determine baseline SCr in the application of RIFLE classification in previous studies 29 Table 9. Estimated baseline SCr 30 Table 10. AKI staging 33 Table 11. Definitions ofAKI,CKD, and AKD 33 Table 12. Examples ofAKI,CKD, and AKD basedonGFR and increases inSCr 35 Table 13. Markers ofkidneydamage inAKD and CKD 35 Table 14. IntegratedapproachtointerpretmeasuresofkidneyfunctionandstructurefordiagnosisofAKI,AKD,andCKD 73 Table 15. CI-AKI risk-scoring model forpercutaneous coronaryintervention 77 Table 16. Additional radiological measurestoreduce CI-AKI 91 Table 17. Potential applications forRRT 91 Table 18. Fluid overloadand outcome in criticallyillchildren with AKI 97 Table 19. Overview oftheadvantages and disadvantages ofdifferent anticoagulants in AKI patients 104 Table 20. Catheter and patientsizes 107 Table 21. Typical setting ofdifferent RRT modalities forAKI (for 70-kg patient) 108 Table 22. Theoretical advantages and disadvantages ofCRRT,IHD, SLED, and PD 112 Table 23. Microbiological quality standards ofdifferent regulatory agencies FIGURES 14 Figure 1. The RIFLE criteriaforAKI 20 Figure 2. Overview ofAKI,CKD, and AKD 20 Figure 3. Conceptual model forAKI 25 Figure 4. Stage-based management ofAKI 26 Figure 5. Evaluation ofAKI accordingtothe stageand cause 34 Figure 6. Chronic Kidney Disease Epidemiology Collaboration cohort changes in eGFR and final eGFR corresponding to KDIGO definitionand stages of AKI 34 Figure 7. GFR/SCralgorithm 38 Figure 8. Conceptual model fordevelopment and clinical course ofAKI 48 Figure 9. Effect offurosemide vs. control onall-cause mortality 48 Figure 10.Effect offurosemide vs. control onneed forRRT 51 Figure 11.Effect oflow-dose dopamineon mortality 52 Figure 12.Effect oflow-dose dopamineon needforRRT 73 Figure 13.Sample questionnaire 78 Figure 14.Riskforcontrast-induced nephropathy 81 Figure 15.Bicarbonate vs. saline and riskofCI-AKI 85 Figure 16.NAC and bicarbonate vs. NACforrisk ofCI-AKI 96 Figure 17.Flow-chart summary ofrecommendations Additionalinformationintheformofsupplementarymaterialscanbefoundonlineathttp://www.kdigo.org/clinical_practice_guidelines/AKI.php iv KidneyInternationalSupplements(2012)2,iv http://www.kidney-international.org &2012KDIGO Notice KidneyInternationalSupplements(2012)2,1;doi:10.1038/kisup.2012.1 SECTIONI: USEOF THECLINICAL PRACTICE GUIDELINE This Clinical Practice Guideline document is based upon the best information available as of February 2011. It is designed to provide information and assist decision-making. It is not intended to define a standard of care, and should not be construed as one, nor should it be interpreted as prescribing an exclusive course of management. Variations in practice will inevitably and appropriately occur when clinicians take into account the needs of individual patients, available resources, and limitations unique to an institution or type of practice. Every health-care professional making use of these recommendations is responsible forevaluating the appropriateness of applying them in the setting of any particular clinical situation. The recommendations for research contained within this document are general and do not imply a specific protocol. SECTIONII: DISCLOSURE KidneyDisease:ImprovingGlobalOutcomes(KDIGO)makeseveryefforttoavoidanyactualor reasonablyperceivedconflictsofinterestthatmayariseasaresultofanoutsiderelationshipora personal,professional,orbusinessinterestofamemberoftheWorkGroup.Allmembersofthe Work Group are required to complete, sign, and submit a disclosure and attestation form showing all such relationships that might be perceived or actual conflicts of interest. This documentisupdatedannuallyandinformationisadjustedaccordingly.Allreportedinformation is published in its entirety at the end of this document in the Work Group members’ Biographical and Disclosure Information section, and is kept on file at the National Kidney Foundation (NKF), Managing Agent for KDIGO. KidneyInternationalSupplements(2012)2,1 1 http://www.kidney-international.org &2012KDIGO Work Group Membership KidneyInternationalSupplements(2012)2,2;doi:10.1038/kisup.2012.2 WORKGROUP CO-CHAIRS John A Kellum, MD, FCCM, FACP Norbert Lameire, MD, PhD University of Pittsburgh School of Medicine Ghent University Hospital Pittsburgh, PA Ghent, Belgium WORKGROUP Peter Aspelin, MD, PhD Alison M MacLeod, MBChB, MD, FRCP Karolinska University Hospital University of Aberdeen Stockholm, Sweden Aberdeen, United Kingdom Rashad S Barsoum, MD, FRCP, FRCPE Ravindra L Mehta, MD, FACP, FASN, FRCP Cairo University UCSD Medical Center Cairo, Egypt San Diego, CA Patrick T Murray, MD, FASN, FRCPI, FJFICMI Emmanuel A Burdmann, MD, PhD UCD School of Medicine and Medical Science University of Sa˜o Paulo Medical School Dublin, Ireland Sa˜o Paulo, Brazil Saraladevi Naicker, MBChB, MRCP, FRCP, Stuart L Goldstein, MD FCP(SA), PhD Cincinnati Children’s Hospital & Medical Center University of the Witwatersrand Cincinnati, OH Johannesburg, South Africa Charles A Herzog, MD Steven M Opal, MD Hennepin County Medical Center Alpert Medical School of Brown University Minneapolis, MN Pawtucket, RI Michael Joannidis, MD Franz Schaefer, MD Medical University of Innsbruck Heidelberg University Hospital Innsbruck, Austria Heidelberg, Germany Andreas Kribben, MD Miet Schetz, MD, PhD University Duisburg-Essen University of Leuven Essen, Germany Leuven, Belgium Andrew S Levey, MD Shigehiko Uchino, MD, PhD Tufts Medical Center Jikei University School of Medicine Boston, MA Tokyo, Japan EVIDENCEREVIEW TEAM Tufts Center for Kidney Disease Guideline Development and Implementation, Tufts Medical Center, Boston, MA, USA: Katrin Uhlig, MD, MS, Project Director; Director, Guideline Development Jose Calvo-Broce, MD, MS, Nephrology Fellow Aneet Deo, MD, MS, Nephrology Fellow Amy Earley, BS, Project Coordinator In addition, support and supervision were provided by: Ethan M Balk, MD, MPH, Program Director, Evidence Based Medicine 2 KidneyInternationalSupplements(2012)2,2 http://www.kidney-international.org &2012KDIGO KDIGO Board Members KidneyInternationalSupplements(2012)2,3;doi:10.1038/kisup.2012.3 Garabed Eknoyan, MD Norbert Lameire, MD, PhD Founding KDIGO Co-Chairs Kai-Uwe Eckardt, MD Bertram L Kasiske, MD KDIGO Co-Chair KDIGO Co-Chair Omar I Abboud, MD, FRCP Michel Jadoul, MD Sharon Adler, MD, FASN Simon Jenkins, MBE, FRCGP Rajiv Agarwal, MD Suhnggwon Kim, MD, PhD Sharon PAndreoli, MD Martin K Kuhlmann, MD Gavin J Becker, MD, FRACP Nathan W Levin, MD, FACP Fred Brown, MBA, FACHE Philip K-T Li, MD, FRCP, FACP Daniel C Cattran, MD, FRCPC Zhi-Hong Liu, MD Allan J Collins, MD, FACP Pablo Massari, MD Rosanna Coppo, MD Peter A McCullough, MD, MPH, FACC, FACP Josef Coresh, MD, PhD Rafique Moosa, MD Ricardo Correa-Rotter, MD Miguel C Riella, MD Adrian Covic, MD, PhD Adibul Hasan Rizvi, MBBS, FRCP JonathanCCraig,MBChB,MM(ClinEpi),DCH,FRACP,PhD Bernardo Rodriquez-Iturbe, MD Angel de Francisco, MD Robert Schrier, MD Paul de Jong, MD, PhD Justin Silver, MD, PhD Ana Figueiredo, RN, MSc, PhD Marcello Tonelli, MD, SM, FRCPC Mohammed Benghanem Gharbi, MD Yusuke Tsukamoto, MD Gordon Guyatt, MD, MSc, BSc, FRCPC Theodor Vogels, MSW David Harris, MD Angela Yee-Moon Wang, MD, PhD, FRCP Lai Seong Hooi, MD Christoph Wanner, MD Enyu Imai, MD, PhD David C Wheeler, MD, FRCP Lesley A Inker, MD, MS, FRCP Elena Zakharova, MD, PhD NKF-KDIGOGUIDELINE DEVELOPMENTSTAFF Kerry Willis, PhD, Senior Vice-President for Scientific Activities Michael Cheung, MA, Guideline Development Director Sean Slifer, BA, Guideline Development Manager KidneyInternationalSupplements(2012)2,3 3 http://www.kidney-international.org &2012KDIGO Reference Keys KidneyInternationalSupplements(2012)2,4;doi:10.1038/kisup.2012.4 NOMENCLATURE ANDDESCRIPTION FORRATING GUIDELINE RECOMMENDATIONS Withineachrecommendation,thestrengthofrecommendationisindicatedasLevel1,Level2,orNotGraded,andthequalityofthe supporting evidenceisshown asA, B,C, orD. Implications Grade* Patients Clinicians Policy Level1 Mostpeopleinyoursituationwould Mostpatientsshouldreceivethe Therecommendationcanbeevaluated ‘‘Werecommend’’ wanttherecommendedcourseofaction recommendedcourseofaction. asacandidatefordevelopingapolicy andonlyasmallproportionwouldnot. oraperformancemeasure. Level2 Themajorityofpeopleinyoursituation Differentchoiceswillbeappropriatefor Therecommendationislikelytorequire ‘‘Wesuggest’’ wouldwanttherecommendedcourse differentpatients.Eachpatientneeds substantialdebateandinvolvement ofaction,butmanywouldnot. helptoarriveatamanagementdecision ofstakeholdersbeforepolicycanbe consistentwithherorhisvaluesand determined. preferences. *Theadditionalcategory‘‘NotGraded’’wasused,typically,toprovideguidancebasedoncommonsenseorwherethetopicdoesnotallowadequateapplicationofevidence. Themostcommonexamplesincluderecommendationsregardingmonitoringintervals,counseling,andreferraltootherclinicalspecialists.Theungradedrecommendations aregenerallywrittenassimpledeclarativestatements,butarenotmeanttobeinterpretedasbeingstrongerrecommendationsthanLevel1or2recommendations. Grade Qualityofevidence Meaning A High Weareconfidentthatthetrueeffectliesclosetothatoftheestimateoftheeffect. B Moderate Thetrueeffectislikelytobeclosetotheestimateoftheeffect,butthereisapossibility thatitissubstantiallydifferent. C Low Thetrueeffectmaybesubstantiallydifferentfromtheestimateoftheeffect. D Verylow Theestimateofeffectisveryuncertain,andoftenwillbefarfromthetruth. CONVERSION FACTORSOF METRICUNITS TO SI UNITS Parameter Metricunits Conversionfactor SIunits Amikacin(serum,plasma) mg/ml 1.708 mmol/l Bloodureanitrogen mg/dl 0.357 mmol/l Calcium,ionized(serum) mg/dl 0.25 mmol/l Creatinine(serum) mg/dl 88.4 mmol/l Creatinineclearance ml/min 0.01667 ml/s Gentamicin(serum) mg/ml 2.09 mmol/l Glucose mg/dl 0.0555 mmol/l Lactate(plasma) mg/dl 0.111 mmol/l Tobramycin(serum,plasma) mg/ml 2.139 mmol/l Urea(plasma) mg/ml 0.167 mmol/l Note:Metricunit (cid:2) conversionfactor=SIunit. 4 KidneyInternationalSupplements(2012)2,4 http://www.kidney-international.org &2012KDIGO Abbreviations and Acronyms KidneyInternationalSupplements(2012)2,5;doi:10.1038/kisup.2012.5 AAMI American Association of Medical HF Hemofiltration Instrumentation HIT Heparin-induced thrombocytopenia ACCP American College of Chest Physicians HR Hazard ratio ACD-A Anticoagulant dextrose solution A i.a. Intraarterial ACE-I Angiotensin-converting enzyme inhibitor(s) ICU Intensive-care unit ADQI Acute Dialysis Quality Initiative IGF-1 Insulin-like growth factor-1 AHCPR Agency for Health Care Policy and Research IHD Intermittent hemodialysis AKD Acute kidney diseases and disorders IIT Intensive insulin therapy AKI Acute kidney injury i.v. Intravenous AKIN Acute Kidney Injury Network KDIGO KidneyDisease:ImprovingGlobalOutcomes ANP Atrial natriuretic peptide KDOQI Kidney Disease Outcomes Quality Initiative aPTT Activated partial thromboplastin time LOS Length of stay ARB Angiotensin-receptor blocker(s) MDRD Modification of Diet in Renal Disease ARF Acute renal failure MI Myocardial infarction ARFTN Acute Renal Failure Trial Network MIC Minimum inhibitory concentration ATN Acute tubular necrosis MRI Magnetic resonance imaging AUC Area under the curve MW Molecular weight BMI Body mass index NAC N-acetylcysteine BUN Blood urea nitrogen NICE-SUGAR NormoglycemiainIntensiveCareEvaluation CDC Centers for Disease Control and Survival Using Glucose Algorithm CHF Congestive heart failure Regulation CI Confidence interval NKD No known kidney disease CI-AKI Contrast-induced acute kidney injury NKF National Kidney Foundation CIT Conventional insulin therapy NSF Nephrogenic Systemic Fibrosis CKD Chronic kidney disease OR Odds ratio CrCl Creatinine clearance PD Peritoneal dialysis CRF Chronic renal failure PICARD Program to Improve Care in Acute Renal CRRT Continuous renal replacement therapy Disease CT Computed tomography RCT Randomized controlled trial CVC Central venous catheters RIFLE Risk, Injury, Failure; Loss, End-Stage Renal CVVH Continuous venovenous hemofiltration Disease CVVHDF Continuous venovenous hemodiafiltration RR Relative risk eCrCl Estimated creatinine clearance RRT Renal replacement therapy EGDT Early goal-directed therapy SAFE Saline vs. Albumin Fluid Evaluation eGFR Estimated glomerular filtration rate SCr Serum creatinine ERT Evidence Review Team ScvO Central venous oxygen saturation 2 ESRD End-stage renal disease SLED Sustained low-efficiency dialysis FDA Food and Drug Administration TCC Tunneled cuffed catheter GFR Glomerular filtration rate VISEP Efficacy of Volume Substitution and Insulin HDF Hemodiafiltration Therapy in Severe Sepsis HES Hydroxyethylstarch KidneyInternationalSupplements(2012)2,5 5 http://www.kidney-international.org &2012KDIGO Abstract KidneyInternationalSupplements(2012)2,6;doi:10.1038/kisup.2012.6 The2011KidneyDisease:ImprovingGlobalOutcomes(KDIGO)ClinicalPracticeGuidelinefor Acute Kidney Injury (AKI) aims to assist practitioners caring for adults and children at risk for or with AKI, including contrast-induced acute kidney injury (CI-AKI). Guideline development followedanexplicitprocessofevidencereviewandappraisal.Theguidelinecontainschapterson definition,riskassessment,evaluation,prevention,andtreatment.DefinitionandstagingofAKI arebasedontheRisk,Injury,Failure;Loss,End-StageRenalDisease(RIFLE)andAcuteKidney Injury Network (AKIN) criteria and studies on risk relationships. The treatment chapters cover pharmacological approachestoprevent or treat AKI,andmanagement ofrenal replacement for kidneyfailurefromAKI.Guidelinerecommendationsarebasedonsystematicreviewsofrelevant trials.Appraisalofthequalityoftheevidenceandthestrengthofrecommendationsfollowedthe GRADE approach. Limitations of the evidence are discussed and specific suggestions are provided for future research. Keywords: Clinical Practice Guideline; KDIGO; acute kidney injury; contrast-induced nephropathy; renal replacement therapy; evidence-based recommendation CITATION Incitingthisdocument,thefollowingformatshouldbeused:KidneyDisease:ImprovingGlobal Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1–138. 6 KidneyInternationalSupplements(2012)2,6 http://www.kidney-international.org &2012KDIGO Foreword KidneyInternationalSupplements(2012)2,7;doi:10.1038/kisup.2012.8 It is our hope that this document will serve several useful Some argue that recommendations should not be made purposes. Our primary goal is to improve patient care. We whenevidenceisweak.However,cliniciansstillneedtomake hope to accomplish this, in the short term, by helping clinical decisions in their daily practice, and they often ask, clinicians know and better understand the evidence (or lack ‘‘What do the experts do in this setting?’’ We opted to give of evidence) that determines current practice. By providing guidance,rather than remainsilent.Theserecommendations comprehensiveevidence-basedrecommendations,thisguide- areoftenratedwithalowstrengthofrecommendationanda line will also help define areas where evidence is lacking and lowstrengthofevidence,or werenotgraded. Itisimportant research is needed. Helping to define a research agenda is an for the users of this guideline to be cognizant of this (see often neglected, but very important, function of clinical Notice). In every case these recommendations are meant to practice guideline development. beaplaceforclinicianstostart,notstop,theirinquiriesinto WeusedtheGRADEsystemtoratethestrengthofevidence specificmanagementquestionspertinenttothepatientsthey and the strength of recommendations. In all, there were only see in daily practice. 11 (18%) recommendations in this guideline for which the We wish to thank the Work Group Co-Chairs, Drs John overallqualityofevidencewasgraded‘A,’whereas20(32.8%) Kellum and Norbert Lameire, along with all of the Work were graded ‘B,’ 23 (37.7%) were graded ‘C,’ and 7 (11.5%) Group members who volunteered countless hours of their weregraded‘D.’Althoughtherearereasonsotherthanquality time developing this guideline. We also thank the Evidence of evidence to make a grade 1 or 2 recommendation, in Review Team members and staff of the National Kidney general, there is a correlation between the quality of overall Foundationwhomadethisprojectpossible.Finally,weowea evidenceandthestrengthoftherecommendation.Thus,there specialdebtofgratitudetothemanyKDIGOBoardmembers were22(36.1%)recommendationsgraded‘1’and39(63.9%) and individuals who volunteered time reviewing the guide- graded ‘2.’ There were 9 (14.8%) recommendations graded line, and making very helpful suggestions. ‘1A,’10(16.4%)were‘1B,’3(4.9%)were‘1C,’and0(0%)were ‘1D.’ There were 2 (3.3%) graded ‘2A,’ 10 (16.4%) were ‘2B,’ 20 (32.8%) were ‘2C,’ and 7 (11.5%) were ‘2D.’ There were Kai-UweEckardt,MD BertramL.Kasiske,MD 26 (29.9%) statements that were not graded. KDIGO Co-Chair KDIGO Co-Chair KidneyInternationalSupplements(2012)2,7 7