OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease VOLUME 2 | ISSUE 4 | AUGUST 2 2012 http://www.kidney-international.org KI_SuppCover_2.4.indd 1 7/11/12 12:00 PM KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease KDIGO gratefully acknowledges the following consortium of sponsors that make our initiatives possible: Abbott, Amgen, Bayer Schering Pharma, Belo Foundation, Bristol-Myers Squibb, Chugai Pharmaceutical, Coca-Cola Company, Dole Food Company, Fresenius Medical Care, Genzyme, Hoffmann-LaRoche, JC Penney, Kyowa Hakko Kirin, NATCO—The Organization for Transplant Professionals, NKF-Board of Directors, Novartis, Pharmacosmos, PUMC Pharmaceutical, Robert and Jane Cizik Foundation, Shire, Takeda Pharmaceutical, Transwestern Commercial Services, Vifor Pharma, and Wyeth. Sponsorship Statement: KDIGO is supported by a consortium of sponsors and no funding is accepted for the development of specific guidelines. http://www.kidney-international.org contents & 2012 KDIGO VOL 2 | ISSUE 4 | AUGUST (2) 2012 KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease v Tables and Figures vi KDIGO Board Members vii Reference Keys viii Abbreviations and Acronyms 279 Notice 280 Foreword 281 Work Group Membership 282 Abstract 283 Summary of Recommendation Statements 288 Chapter 1: Diagnosis and evaluation of anemia in CKD 292 Chapter 2: Use of iron to treat anemia in CKD 299 Chapter 3: Use of ESAs and other agents to treat anemia in CKD 311 Chapter 4: Red cell transfusion to treat anemia in CKD 317 Methods for Guideline Development 324 Biographic and Disclosure Information 330 Acknowledgments 331 References http://www.kidney-international.org contents & 2012 KDIGO TABLES 289 Table 1. Hb levels in children between 1–19 years for initiation of anemia workup 289 Table 2. Hb levels in children between birth and 24 months for initiation of anemia workup 307 Table 3. Potentially correctable versus non correctable factors involved in the anemia of CKD, in addition to ESA deficiency 308 Table 4. Practical approach in presence of ESA hyporesponsiveness 312 Table 5. Estimated risk associated with blood transfusions per unit transfused 312 Table 6. Estimated risk of transfusion-related infections per unit transfused 314 Table 7. Indications for blood transfusions 318 Table 8. Systematic review topics and screening criteria 318 Table 9. Hierarchy of importance of outcomes 319 Table 10. Literature search yield of primary articles for systematic review topics 319 Table 11. Classification of study quality 320 Table 12. GRADE system for grading quality of evidence 320 Table 13. Final grade for overall quality of evidence 321 Table 14. Balance of benefits and harm 321 Table 15. KDIGO nomenclature and description for grading recommendations 321 Table 16. Determinants of strength of recommendation 322 Table 17. The Conference on Guideline Standardization (COGS) checklist for reporting clinical practice guidelines FIGURES 293 Figure 1. Receiver operating characteristic (ROC) curves, examining the utility of iron status tests to distinguish iron deficient from nondeficient study patients 294 Figure 2. Sensitivity and specificity of TSAT and serum ferritin and their combination (TSAT + ferritin) and bone marrow iron (BM iron) to identify correctly a positive erythropoietic response (Z1-g/dl [Z10-g/l] increase in Hb [DHb]) to intravenous iron in 100 nondialysis patients with CKD (areas under the ROCs) 313 Figure 3. Lymphocytotoxic antibody reactivity against random donor test panel in relation to the number of blood transfusions 315 Figure 4. Algorithms for red cell transfusion use in CKD patients Additional information in the form of supplementary materials can be found online at http://www.kdigo.org/clinical_practice_guidelines/anemia.php Kidney International Supplements (2012) 2,v v http://www.kidney-international.org & 2012 KDIGO KDIGO Board Members Garabed Eknoyan, MD Norbert Lameire, MD, PhD Founding KDIGO Co-Chairs Kai-Uwe Eckardt, MD Immediate Past Co-Chair Bertram L Kasiske, MD David C Wheeler, MD, FRCP 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 P Andreoli, 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 Jonathan C Craig, MBChB, MM (Clin Epi), 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 Elena Zakharova, MD, PhD Lesley A Inker, MD, MS, FRCP 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 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. Implications Grade* Patients Clinicians Policy Level 1 Most people in your situation would Most patients should receive the recommended The recommendation can be evaluated ‘We recommend’ want the recommended course of action course of action. as a candidate for developing a policy or and only a small proportion would not. a performance measure. Level 2 The majority of people in your situation Different choices will be appropriate for different The recommendation is likely to require ‘We suggest’ would want the recommended course of patients. Each patient needs help to arrive at a substantial debate and involvement of action, management decision consistent with her or his stakeholders before policy can be but many would not. values and preferences. 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 declarative statements, but are not meant to be interpreted as being stronger recommendations than Level 1 or 2 recommendations. 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. STAGES OF CHRONIC KIDNEY DISEASE CKD Stage Description GFR (ml/min per 1.73 m2) 1 Kidney damage with normal or increased GFR Z90 2 Kidney damage with mild decreased GFR 60–89 3 Moderate decreased GFR 30–59 4 Severe decreased GFR 15–29 5a Kidney failure o15 (or dialysis) CKD, chronic kidney disease; GFR, glomerular filtration rate. CKD 1–5T notation applies to kidney transplant recipients. a5D if dialysis (HD or PD). CURRENT CHRONIC KIDNEY DISEASE (CKD) NOMENCLATURE USED BY KDIGO CKD Categories Definition CKD CKD of any stage (1–5), with or without a kidney transplant, including both non-dialysis dependent CKD (CKD 1–5ND) and dialysis-dependent CKD (CKD 5D) CKD ND Non-dialysis-dependent CKD of any stage (1–5), with or without a kidney transplant (i.e., CKD excluding CKD 5D) CKD T Non-dialysis-dependent CKD of any stage (1–5) with a kidney transplant Specific CKD Stages CKD 1, 2, 3, 4 Specific stages of CKD, CKD ND, or CKD T CKD 3-4, etc. Range of specific stages (e.g., both CKD 3 and CKD 4) CKD 5D Dialysis-dependent CKD 5 CKD 5HD Hemodialysis-dependent CKD 5 CKD 5PD Peritoneal dialysis-dependent CKD 5 CONVERSION FACTORS OF METRIC UNITS TO SI UNITS Parameter Metric units Conversion factor SI units Ferritin ng/ml 1 mg/l Hemoglobin g/dl 10 g/l Kidney International Supplements (2012) 2, vii vii http://www.kidney-international.org & 2012 KDIGO Abbreviations and Acronyms D Change HEMO Study Kidney Disease Clinical Studies Initiative AGREE Appraisal of Guidelines for Research and Hemodialysis Study Evaluation HLA Human leukocyte antigen BM Bone marrow HR Hazard ratio CBC Complete blood count IM Intramuscular CERA Continuous erythropoietin receptor activator IU International unit CHOIR Correction of Hemoglobin and Outcomes in IV Intravenous Renal Insufficiency KDIGO Kidney Disease: Improving Global Outcomes CI Confidence interval KDOQI Kidney Disease Outcomes Quality Initiative CKD Chronic kidney disease Kt/V Clearance expressed as a fraction of urea or CKiD Chronic Kidney Disease in Children body water volume Prospective Cohort Study MCH Mean