VOLUME 2 | ISSUE 2 | JUNE 2012 http://www.kidney-international.org Official JOurnal Of the internatiOnal SOciety Of nephrOlOgy KDIGO Clinical Practice Guideline for Glomerulonephritis KDIGO Clinical Practice Guideline for Glomerulonephritis KDIGO gratefully acknowledges the following consortium of sponsors that make our initiatives possible: Abbott, Amgen, Belo Foundation, Coca-Cola Company, Dole Food Company, Genzyme, Hoffmann-LaRoche, JC Penney, NATCO—The Organization for Transplant Professionals, NKF-Board of Directors, Novartis, Robert and Jane Cizik Foundation, Roche, Shire, Transwestern Commercial Services, and Wyeth. Sponsorship Statement: KDIGO is supported by a consortium of sponsors and no funding is accepted for the development of specific guidelines. KDIGO Clinical Practice Guideline for Glomerulonephritis Tablesv KDIGO Board Membersvi Reference Keysvii Abbreviations and Acronymsviiii Notice139 Foreword140 Work Group Membership141 Abstract142 Summary of Recommendation Statements143 Chapter 1: Introduction154 Chapter 2: General principles in the management of glomerular disease156 Chapter 3: Steroid-sensitive nephrotic syndrome in children163 Chapter 4: Steroid-resistant nephrotic syndrome in children172 Chapter 5: Minimal-change disease in adults177 Chapter 6: Idiopathic focal segmental glomerulosclerosis in adults181 Chapter 7: Idiopathic membranous nephropathy186 Chapter 8: Idiopathic membranoproliferative glomerulonephritis198 Chapter 9: Infection-related glomerulonephritis200 Chapter 10: Immunoglobulin A nephropathy209 Chapter 11: Henoch-Scho ¨ nlein purpura nephritis218 Chapter 12: Lupus nephritis221 Chapter 13: Pauci-immune focal and segmental necrotizing glomerulonephritis233 Chapter 14: Anti-glomerular basement membrane antibody glomerulonephritis240 Methods for guideline development243 Biographic and Disclosure Information252 Acknowledgments258 References259 http://www.kidney-international.org contents & 2012 KDIGO VOL 2 | SUPPLEMENT 2 | JUNE 2012 TABLES Table 1. Definitions of nephrotic syndrome in children164 Table 2. Meta-analyses of RCTs of corticosteroid-sparing agents in children with FR or SD SSNS167 Table 3. RCTs comparing corticosteroid-sparing agents in FR and SD SSNS168 Table 4. Advantages and disadvantages of corticosteroid-sparing agents as first agent for use in FR or SD SSNS169 Table 5. CNI trials in SRNS174 Table 6. Remission in corticosteroid-treated control arms of SRNS randomized trials175 Table 7. Cytotoxic therapy in SRNS175 Table 8. Dosage regimens in MCD178 Table 9. Causes of FSGS182 Table 10. Definitions of nephrotic syndrome in adults with FSGS183 Table 11. Treatment schedules184 Table 12. Reported causes of secondary MN (% in adults)187 Table 13. Reported causes of secondary MN188 Table 14. Definitions of complete and partial remission in IMN188 Table 15. Cyclical corticosteroid/alkylating-agent therapy for IMN (the "Ponticelli Regimen")189 Table 16. Risks and benefits of the cyclical corticosteroid/alkylating-agent regimen in IMN190 Table 17. Contraindications to the use of the cyclical corticosteroid/alkylating-agent regimen in IMN191 Table 18. CNI-based regimens for IMN192 Table 19. Pediatric MN studies197 Table 20. Underlying conditions associated with a membranoproliferative pattern of GN199 Table 21. Infections associated with glomerulonephritis201 Table 22. Treatment of HCV infection according to stages of CKD203 Table 23. Dosage adjustment of drugs for HBV infection according to kidney function (endogenous CrCl)204 Table 24. The spectrum of kidney disease in HIV-infected patients205 Table 25. A clinicopathological classification of schistosomal glomerulopathy206 Table 26. Corticosteroid regimens in patients with IgAN211 Table 27. Definitions of response to therapy in LN222 Table 28. Regimens for initial therapy in class III/class IV LN223 Table 29. Criteria for the diagnosis and classification of relapses of LN229 Table 30. Recommended treatment regimens for ANCA vasculitis with GN234 Table 31. Therapy of anti-GBM GN241 Table 32. Screening criteria for systematic review topics of nontreatment and treatment244 Table 33. Literature search yield of RCTs248 Table 34. Hierarchy of outcomes248 Table 35. Classification of study quality249 Table 36. GRADE system for grading quality of evidence250 Table 37. Final grade for overall quality of evidence250 Table 38. Balance of benefits and harm250 Table 39. KDIGO nomenclature and description for grading recommendations251 Table 40. Determinants of strength of recommendation251 Additional information in the form of supplementary materials can be found online at http://www.kdigo.org/clinical_practice_guidelines/GN.php http://www.kidney-international.org contents & 2012 KDIGO Kidney International Supplements (2012) 2,v v KDIGO Board Members Garabed Eknoyan, MD Norbert Lameire, MD, PhD Founding KDIGO Co-Chairs Kai-Uwe Eckardt, MD KDIGO Co-Chair Bertram L Kasiske, MD KDIGO Co-Chair Omar I Abboud, MD, FRCP Sharon Adler, MD, FASN Rajiv Agarwal, MD Sharon P Andreoli, MD Gavin J Becker, MD, FRACP Fred Brown, MBA, FACHE Daniel C Cattran, MD, FRCPC Allan J Collins, MD, FACP Rosanna Coppo, MD Josef Coresh, MD, PhD Ricardo Correa-Rotter, MD Adrian Covic, MD, PhD Jonathan C Craig, MBChB, MM (Clin Epi), DCH, FRACP, PhD Angel de Francisco, MD Paul de Jong, MD, PhD Ana Figueiredo, RN, MSc, PhD Mohammed Benghanem Gharbi, MD Gordon Guyatt, MD, MSc, BSc, FRCPC David Harris, MD Lai Seong Hooi, MD Enyu Imai, MD, PhD Lesley A Inker, MD, MS, FRCP Michel Jadoul, MD Simon Jenkins, MBE, FRCGP Suhnggwon Kim, MD, PhD Martin K Kuhlmann, MD Nathan W Levin, MD, FACP Philip K-T Li, MD, FRCP, FACP Zhi-Hong Liu, MD Pablo Massari, MD Peter A McCullough, MD, MPH, FACC, FACP Rafique Moosa, MD Miguel C Riella, MD Adibul Hasan Rizvi, MBBS, FRCP Bernardo Rodriquez-Iturbe, MD Robert Schrier, MD Justin Silver, MD, PhD Marcello Tonelli, MD, SM, FRCPC Yusuke Tsukamoto, MD Theodor Vogels, MSW Angela Yee-Moon Wang, MD, PhD, FRCP Christoph Wanner, MD David C Wheeler, MD, FRCP Elena Zakharova, MD, PhD NKF-KDIGO GUIDELINE DEVELOPMENT STAFF Kerry Willis, PhD, Senior Vice-President for Scientific Activities Michael Cheung, MA, Guideline Development Director Sean Slifer, BA, Guideline Development Manager Kidney International Supplements (2012) 2,vi vi http://www.kidney-international.org & 2012 KDIGO Reference Keys Grade* Implications Patients Clinicians Policy Level 1 ‘‘We recommend’’ Most people in your situation would want the recommended course of action and only a small proportion would not. Most patients should receive the recommended course of action. The recommendation can be evaluated as a candidate for developing a policy or a performance measure. Level 2 ‘‘We suggest’’ The majority of people in your situation would want the recommended course of action, but many would not. Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with her or his values and preferences. The recommendation is likely to require substantial debate and involvement of stakeholders before policy can be determined. *The additional category ‘‘Not Graded’’ was used, typically, to provide guidance based on common sense or where the topic does not allow adequate application of evidence. The most common examples include recommendations regarding monitoring intervals, counseling, and referral to other clinical specialists. The ungraded recommendations are generally written as simple decl arative statements, but are not meant to be interpreted as being stronger recommendations than Level 1 or 2 recommendations. CONVERSION FACTORS OF METRIC UNITS TO SI UNITS NOMENCLATURE AND DESCRIPTION FOR RATING GUIDELINE RECOMMENDATIONS Within each recommendation, the strength of recommendation is indicated as Level 1, Level 2,orNot Graded, and the quality of the supporting evidence is shown as A, B, C,orD. Parameter Metric units Conversion factor SI units Albumin (serum) g/dl 10 g/l Creatinine (serum) mg/dl 88.4 mmol/l Creatinine clearance ml/min 0.01667 ml/s Cyclosporine (serum) ng/ml 0.832 nmol/l uPCR mg/g 0.1 mg/mmol Note: Metric unit  conversion factor ¼ SI unit. Grade Quality of evidence Meaning A High We are confident that the true effect lies close to that of the estimate of the effect. B Moderate The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. C Low The true effect may be substantially different from the estimate of the effect. D Very Low The estimate of effect is very uncertain, and often will be far from the truth. Kidney International Supplements (2012) 2, vii vii http://www.kidney-international.org & 2012 KDIGO Kidney International Supplements (2012) 2, viii viii Abbreviations and Acronyms ACE-I Angiotensin-converting enzyme inhibitor(s) ACTH Adrenocorticotropic hormone AKI Acute kidney injury ALMS Aspreva Lupus Managemen t Study ANCA Antineutrophil cytoplasmic antibody APOL1 Apolipoprotein L1 APS Antiphospholipid antibody syndrome ARB Angiotensin-receptor blocker ATN Acute tubular necrosis BMI Body mass index CI Confidence interval CKD Chronic kidney disease CNI Calcineurin inhibitor CrCl Creatinine clearance eGFR Estimated glomerular filtration rate ERT Evidence Review Team ESRD End-stage renal disease FR Frequently relapsing FRNS Frequently relapsing nephrotic syndrome FSGS Focal segmental glomerulosclerosis GBM Glomerular basement membrane GFR Glomerular filtration rate GN Glomerulonephritis GRADE Grading of Recommendations Assessment, Development and Evaluation HAART Highly active antiretroviral therapy HBV Hepatitis B virus HCV Hepatitis C virus HIVAN Human immunodeficiency virus–associated nephropathy HR Hazards ratio HSP Henoch-Scho ¨ nlein purpura HSV Herpes simplex virus i.v. Intravenous IgAN Immunoglobulin A nephropathy IMN Idiopathic membranous nephropathy INR International normalized ratio ISKDC International Study of Kidney Disease in Children IU International units KDIGO Kidney Disease: Improving Global Outcomes LN Lupus nephritis MCD Minimal-change disease MDRD Modification of Diet in Renal Disease MEPEX Methylprednisolone or Plasma Exchange MMF Mycophenolate mofetil MN Membranous nephropathy MPGN Membranoproliferative glomerulonephritis MPO Myeloperoxidase NCGN Necrotizing and crescentic glomerulonephritis NS Not significant OR Odds ratio PCR Protein-creatinine ratio p.o. Oral(ly) PR3 Proteinase 3 RAS Renin-angiotensin system RAVE Rituximab for the Treatment of Wegener’s Granulomatosis and Microsc opic Polyangiitis RCT Randomized controlled trial RR Relative risk RRT Renal replacement therapy SCr Serum creatinine SD Steroid-dependent SLE Systemic lupus erythematosus SRNS Steroid-resistant nephrotic syndrome SSNS Steroid-sensitive nephrotic syndrome TMA Thrombotic microangiopathies TTP Thrombotic thrombocytopenic purpura uPCR Urine protein:creatinine ratio http://www.kidney-international.org & 2012 KDIGO Notice Kidney International Supplements (2012) 2, 139; doi:10.1038/kisup.2012.9 SECTION I: USE OF THE CLINICAL PRACTICE GUIDELINE This Clinical Practice Guideline document is based upon systematic literature searches last conducted in January 2011, supplemented with additional evidence through November 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 for evaluating 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. SECTION II: DISCLOSURE Kidney Disease: Improving Global Outcomes (KDIGO) makes every effort to avoid any actual or reasonably perceived conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the Work Group. All members of the 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 document is updated annually and information is adjusted accordingly. All reported information will be printed in the final publication and are on file at the National Kidney Foundation (NKF), Managing Agent for KDIGO. http://www.kidney-international.org & 2012 KDIGO KDIGO gratefully acknowledges the following consortium of sponsors that make our initiatives possible: Abbott, Amgen, Belo Foundation, Coca-Cola Company, Dole Food Company, Genzyme, Hoffmann-LaRoche, JC Penney, NATCO—The Organization for Transpla nt Professionals, NKF-Board of Directors, Novartis, Robert and Jane Cizik Foundation, Roche, Shire, Transwestern Commercial Services, and Wyeth. KDIGO is supported by a consor tium of sponsors and no funding is accepted for the development of specific guidelines. Kidney International Supplements (2012) 2, 139 139 Foreword Kidney International Supplements (2012) 2, 140; doi:10.1038/kisup.2012.10 It is our hope that this document will serve several useful purposes. Our primary goal is to improve patient care. We hope to accomplish this, in the short term, by helping clinicians know and better understand the evidence (or lack of evidence) that determines current practice. By providing comprehensive evidence-based recommendations, this guide - line will also help define areas where evidence is lacking and research is needed. Helping to define a research agenda is an often neglected, but very important, function of clinical practice guideline development. We used the GRADE system to rate the strength of evidence and the strength of recommendations. In all, there were only 4 (2%) recommendations in this guideline for which the overall quality of evidence was graded ‘A’, whereas 34 (20%) were graded ‘B’, 66 (40%) were graded ‘C’, and 63 (38%) were graded ‘D’. Although there are reasons other than quality of evidence to make a grade 1 or 2 recommendation, in general, there is a correlation between the quality of overall evidence and the strength of the recommendation. Thus, there were 46 (28%) recommendations graded ‘1’ and 121 (72%) graded ‘2’. There were 4 (2%) recommendations graded ‘1A’, 24 (14%) were ‘1B’, 15 (9%) w ere ‘1C’, and 3 (2%) were ‘1D’. There were 0 (0%) graded ‘2A’, 10 (6%) were ‘2B’, 51 (31%) were ‘2C’, and 60 (36%) were ‘2D’. There were 28 (14%) statements that were not graded. Some argue that recommendations should not be made when evidence is weak. However, clinicians still need to make clinical decisions in their daily practice, and they often ask, ‘‘What do the experts do in this setting?’’ We opted to give guidance, rather than remain silent. The se recommendations are often rated with a low strength of recommendation and a low strength of evidence, or were not graded. It is important for the users of this guideline to be cognizant of this (see Notice). In every case these recommendations are meant to be a place for clinicians to start, not stop, their inquiries into specific management questions pertinent to the patients they see in daily practice. We wish to thank the Work Group Co-Chairs, Drs. Dan Cattran and John Feehally, along w ith all of the Work Group members who volunteered countless hours of their time developing this guideline. We also thank the Evidence Review Team members and staff of the National Kidney Foundation who made this project possible. Finally, we owe a special debt of gratitude to the many KDIGO Board members and individuals who volunteered time reviewing the guideline, and making very helpful suggestions. Kai-Uwe Eckardt, MD Bertram L Kasiske, MD KDIGO Co-Chair KDIGO Co-Chair http://www.kidney-international.org & 2012 KDIGO 140 Kidney International Supplements (2012) 2,140 Work Group Membership Kidney International Supplements (2012) 2, 141; doi:10.1038/kisup.2012.11 http://www.kidney-international.org & 2012 KDIGO WORK GROUP CO-CHAIRS Daniel C Cattran, MD, FRCPC Toronto General Hospital Toronto, Canada John Feehally, DM, FRCP University Hospitals of Leicester Leicester, United Kingdom WORK GROUP EVIDENCE REVIEW TEAM Tufts Center for Kidney Disease Guideline Development and Implementation, Tufts Medical Center, Boston, MA, USA: Ethan M Balk, MD, MPH, Project Director; Program Director, Evidence Based Medicine Gowri Raman, MD, MS, Scientific Staff Dana C Miskulin, MD, MS, Staff Nephrologist Aneet Deo, MD, MS, Nephrology Fellow Amy Earley, BS, Project Coordinator Shana Haynes, MS, DHSc, Research Assistant In addition, support and supervision were provided by: Katrin Uhlig, MD, MS, Director, Guideline Development H Terence Cook, MBBS, MRCP, MRCPath, FRCPath, FMedSci Zhi-Hong Liu, MD Imperial College London Nanjing University School of Medicine London, United Kingdom Nanjing, China Fernando C Fervenza, MD, PhD Sergio A Mezzano, MD, FASN, FACP Mayo Clinic Universidad Austral Rochester, MN, USA Valdivia, Chile Ju ¨ rgen Floege, MD Patrick H Nachman, MD University Hospital, RWTH Aachen University of North Carolina Aachen, Germany Chapel Hill, NC, USA Debbie S Gipson, MD, MS Manuel Praga, MD, PhD University of Michigan Hospital 12 de Octubre Ann Arbor, MI, USA Madrid, Spain Richard J Glassock, MD, MACP Jai Radhakrishnan, MD, MS, MRCP, FACC, FASN The Geffen School of Medicine at UCLA New York Presbyterian-Columbia Laguna Niguel, CA, USA New York, NY, USA Elisabeth M Hodson, MBBS, FRACP Brad H Rovin, MD, FACP, FASN The Children’s Hospital at Westmead The Ohio State University College of Medicine Sydney, Australia Columbus, OH, USA Vivekanand Jha, MD, DM, FRCP, FAMS Ste ´ phan Troyanov, MD Postgraduate Institute of Medical Education University of Montreal Chandigarh, India Montreal, Canada Philip Kam-Tao Li, MD, FRCP, FACP Jack F M Wetzels, MD, PhD Chinese University of Hong Kong Radboud University Nijmegen Medical Center Hong Kong, China Nijmegen, The Netherlands Kidney International Supplements (2012) 2, 141 141 [...]... specific suggestions are provided for future research Keywords: Clinical Practice Guideline; KDIGO; glomerulonephritis; nephrotic syndrome; evidence-based recommendation; systematic review CITATION In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group KDIGO Clinical Practice Guideline for Glomerulonephritis Kidney inter.,...http://www.kidney-international.org & 2012 KDIGO Abstract Kidney International Supplements (2012) 2, 142; doi:10.1038/kisup.2012.12 The 2011 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Glomerulonephritis (GN) aims to assist practitioners caring for adults and children with GN Guideline development followed an explicit process of evidence review and appraisal The guideline contains chapters... guideline was written primarily for nephrologists, although it should also be useful for other physicians, nurses, pharmacists, and health-care professionals who care for patients with GN It was not developed for health-care administrators or regulators per se, and no attempts were made to develop clinical performance measures This guideline was also not written directly for patients or caregivers, though... discussed in the relevant chapters The evidence for renal protective therapy will be the subject of a forthcoming KDIGO Clinical Practice Guideline on Evaluation and Management of Chronic Kidney Disease Hyperlipidemia Treatment of hyperlipidemia in patients with glomerular disease should usually follow the guidelines that apply to those at high risk for the development of cardiovascular disease This... Infection-related glomerulonephritis 9.1: For the following infection-related GN, we suggest appropriate treatment of the infectious disease and standard approaches to management of the kidney manifestations: (2D) K poststreptococcal GN; K infective endocarditis-related GN; K shunt nephritis 9.2: Hepatitis C virus (HCV) infection–related GN (Please also refer to the published KDIGO Clinical Practice Guidelines for. .. locally available standards The evidence for blood pressure goals and choice of antihypertensive therapy in GN and other CKD has not been systematically evaluated for this guideline; it will be the subject of a forthcoming KDIGO Clinical Practice Guideline Proteinuria Reduction in proteinuria is important, as it reflects control of the primary disease, reduction of glomerular hypertension, and also reduction... undetectable for a minimum of 6 months (Not Graded) Kidney International Supplements (2012) 2, 143–153 153 chapter 1 http://www.kidney-international.org & 2012 KDIGO Chapter 1: Introduction Kidney International Supplements (2012) 2, 154–155; doi:10.1038/kisup.2012.14 SCOPE This clinical practice guideline has been developed to provide recommendations for the treatment of patients already diagnosed with glomerulonephritis. .. should be an integral part of the therapy for blood pressure control The ideal goal for blood pressure is not firmly established but current recommendations suggest that 130/80 mm Hg should be the treatment goal There are limited data to support a lower target of 125/75 mm Hg if there is proteinuria 41 g/d.7 This issue will be covered in a forthcoming KDIGO Guideline for the Management of Blood Pressure... in this guideline are directed by the available evidence to support the specific treatment options listed When the published evidence is very weak or nonexistent no recommendations are made, although the reasons for such omissions are explained in the rationale in each chapter There are, therefore, a number of circumstances in this guideline where treatments in wide use in current clinical practice. .. We suggest oral cyclophosphamide 2–2.5 mg/kg/d for 8 weeks (2C) 5.2.2: We suggest CNI (cyclosporine 3–5 mg/kg/d or tacrolimus 0.05–0.1 mg/kg/d in divided doses) for 1–2 years for FR/SD MCD patients who have relapsed despite cyclophosphamide, or for people who wish to preserve their fertility (2C) 5.2.3: We suggest MMF 500–1000 mg twice daily for 1–2 years for patients who are intolerant of corticosteroids, . SOciety Of nephrOlOgy KDIGO Clinical Practice Guideline for Glomerulonephritis KDIGO Clinical Practice Guideline for Glomerulonephritis KDIGO gratefully acknowledges. following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis.