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VOLUME 2
|
ISSUE 2
|
JUNE 2012
http://www.kidney-international.org
Official JOurnal Of the internatiOnal SOciety Of nephrOlOgy
KDIGO ClinicalPracticeGuidelinefor Glomerulonephritis
KDIGO ClinicalPractice 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 ClinicalPracticeGuidelinefor 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 forguideline 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 CLINICALPRACTICE GUIDELINE
This ClinicalPracticeGuideline 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: ClinicalPractice 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 PracticeGuidelinefor 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 PracticeGuidelinefor 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 KDIGOClinicalPracticeGuideline 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 KDIGOClinicalPracticeGuideline 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 clinicalpracticeguideline 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 KDIGOGuidelinefor 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.