AJKD
`
`American Journal of
`Kidney Diseases
`
`VOL 47, NO 5, SUPPL 3, MAY 2006
`
`CONTENTS
`
`KDOQI Clinical Practice Guidelines and Clinical
`Practice Recommendations for Anemia in Chronic
`Kidney Disease
`Tables ...............................................................................................................................
`
`S1
`
`Figures .............................................................................................................................
`
`Abbreviations and Acronyms ........................................................................................
`
`Work Group Membership ...............................................................................................
`
`KDOQI Advisory Board Members..................................................................................
`
`Foreword..........................................................................................................................
`
`I. EXECUTIVE SUMMARY
`
`II. CLINICAL PRACTICE GUIDELINES AND CLINICAL PRACTICE RECOMMEN-
`DATIONS FOR ANEMIA IN CHRONIC KIDNEY DISEASE IN ADULTS
`1.1. Identifying Patients and Initiating Evaluation ....................................................
`1.2. Evaluation of Anemia in CKD.............................................................................
`2.1. Hb Range ............................................................................................................
`3.1. Using ESAs .........................................................................................................
`3.2. Using Iron Agents...............................................................................................
`3.3. Using Pharmacological and Nonpharmacological Adjuvants to ESA Treatment
`in HD-CKD.........................................................................................................
`3.4. Transfusion Therapy ..........................................................................................
`3.5. Evaluating and Correcting Persistent Failure To Reach or Maintain Intended
`Hb.......................................................................................................................
`
`III. CLINICAL PRACTICE RECOMMENDATIONS FOR ANEMIA IN CHRONIC KID-
`NEY DISEASE IN CHILDREN
`1.1: Identifying Patients and Initiating Evaluation ....................................................
`1.2: Evaluation of Anemia in CKD.............................................................................
`2.1: Hb Range ............................................................................................................
`
`S2
`
`S4
`
`S7
`
`S8
`
`S9
`
`S11
`
`S16
`S17
`S28
`S33
`S54
`S58
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`S71
`S79
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`S81
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`S86
`S87
`S89
`S90
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`3.1: Using ESAs .........................................................................................................
`3.2: Using Iron Agents...............................................................................................
`3.3: Using Pharmacological and NonPharmacological Adjuvants to ESA Treatment
`in HD-CKD.........................................................................................................
`3.4: Transfusion Therapy ..........................................................................................
`3.5: Evaluating and Correcting Persistent Failure To Reach or Maintain Intended
`Hb Level .............................................................................................................
`
`IV. CLINICAL PRACTICE RECOMMENDATIONS FOR ANEMIA IN CHRONIC KID-
`NEY DISEASE IN TRANSPLANT RECIPIENTS
`
`V. APPENDIX 1: METHODS OF EVIDENCE REVIEW AND SYNTHESIS ...................
`
`Work Group Biographies.............................................................................................
`
`Acknowledgments .......................................................................................................
`
`References....................................................................................................................
`
`S93
`S99
`
`S105
`S106
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`S107
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`S109
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`S117
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`S126
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`S131
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`S132
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`
`KDOQI Disclaimer
`
`SECTION I: USE OF THE CLINICAL PRACTICE GUIDELINES AND CLINICAL PRACTICE
`RECOMMENDATIONS
`
`These Clinical Practice Guidelines (CPGs) and Clinical Practice Recommendations (CPRs) are
`based upon the best information available at the time of publication. They are designed to provide
`information and assist decision-making. They are not intended to define a standard of care, and
`should not be construed as one. Neither should they 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 CPGs and CPRs 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: DEVELOPMENT PROCESS
`
`The National Kidney Foundation makes every effort to avoid any actual or potential 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.
`Specifically, all members of the Work Group are required to complete, submit and sign a
`Disclosure Questionnaire showing all such relationships that might be perceived as real or potential
`conflicts of interest. All affiliations are published in their entirety at the end of this publication in the
`Biographical Sketch section of the Work Group members.
`
`In citing this document, the following format should be used: National Kidney Foundation. KDOQI
`Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney
`Disease. Am J Kidney Dis 47:S1-S146, 2006 (suppl 3).
`
`Support for the development of the KDOQI Clinical Practice Guidelines and Clinical Practice
`Recommendations for Anemia in Chronic Kidney Disease was provided by Amgen, Inc.
`
`The National Kidney Foundation gratefully acknowledges the support of Amgen, Inc. as the
`founding and principal sponsor of KDOQI.
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`
`Tables
`
`Table 1.
`
`Table 2.
`Table 3.
`Table 4.
`Table 5.
`Table 6.
`
`Key Differences Between Current Guidelines (KDOQI Anemia 2006) and
`Previous Anemia Guidelines (KDOQI 2000 and EBPG 2004) ...................................... S15
`Relationship Between Hb Level and Kidney Function ................................................. S18
`Relationship Between Hct and Kidney Function............................................................ S19
`Prevalence of Anemia by Level of Kidney Function...................................................... S20
`Difference in Hb and Hct From Reference by Category of CCr...................................... S20
`Difference in Hb and Hct From Reference According to Category of BSA
`and Normalized eGFR ........................................................................................... S21
`Hb for Males by Race/Ethnicity and Age: United States, 1988 to 1994......................... S24
`Table 7.
`Hb for Females by Race/Ethnicity and Age: United States, 1988 to 1994 ..................... S25
`Table 8.
`Normal Increase in Hb Levels Related to Long-Term Altitude Exposure ...................... S26
`Table 9.
`Table 10. Maximum Hb Cutoff Values for Anemia in Pregnancy.................................................. S27
`Table 11.
`Adjustment to Hb for Smoking by Number of Packets per Day..................................... S27
`Table 12.
`RCTs Examining Effects of Distinct Hb Targets/Levels on Key Clinical Outcomes
`in the HD-CKD and PD-CKD Populations .................................................................... S34
`RCTs Examining Effects of Distinct Hb Targets/Levels on QOL in the HD-CKD
`and PD-CKD Populations............................................................................................... S36
`Non-CVD/Mortality AE Rates in RCTs Examining Distinct Hb Targets/Levels
`in HD-CKD and PD-CKD Populations: ESA versus ESA ............................................. S38
`Non-CVD/Mortality AE Rates in RCTs Examining Distinct Hb Targets/Levels
`in the HD-CKD and PD-CKD Populations: ESA versus Placebo .................................. S40
`Effects of Distinct Hb Targets/Levels on Key Clinical Outcomes in the
`ND-CKD Population ...................................................................................................... S41
`RCTs Examining Effects of Distinct Hb Targets/Levels on QOL in the
`ND-CKD Population ...................................................................................................... S42
`Non-CVD/Mortality AE Rates in RCTs Examining Distinct Hb Targets/Levels
`in the CKD Population .......................................................................................... S43
`RCTs Examining Effects of Distinct Hb Targets/Levels on Exercise Capacity
`in the HD-CKD and PD-CKD Populations .................................................................... S44
`Target Hb Levels in the HD-CKD and PD-CKD Populations........................................ S45
`Target Hb Levels in the ND-CKD Population................................................................ S48
`Anemia Management Protocol Information for Initial Anemia Management
`Used in ESA RCTs ................................................................................................ S56
`RCTs for Ferritin and TSAT Targets in the HD-CKD Population .................................. S60
`Value of Baseline Ferritin for Assessing Likelihood of Response to IV Iron Therapy
`in the HD-CKD Population ............................................................................................ S61
`Value of Ferritin in Assessing Iron Storage Excess or Deficiency.................................. S61
`Value of Baseline TSAT for Assessing Likelihood of Response to IV Iron Therapy
`in the HD-CKD Population ............................................................................................ S62
`Value of Baseline CHr for Assessing Likelihood of Response to IV Iron Therapy........ S62
`Table 27.
`Table 28. Mean Monthly Dose of Iron in Adult Prevalent HD-CKD Patients on ESA Therapy.... S63
`Table 29A. Comparative RCTs of IV versus PO Iron Administration and Efficacy of
`Anemia Management in the HD-CKD and PD-CKD Populations ................................. S65
`Table 29B. Comparative RCTs of IV versus PO Iron Administration and Efficacy of
`Anemia Management in the ND-CKD Population ......................................................... S65
`Comparative RCTs of PO Iron Administration versus Placebo/Control and
`Efficacy of Anemia Management in the HD-CKD and PD-CKD Populations .................... S66
`Serious AEs of Iron Agents in Patients Naïve to Tested Iron Agent (N ⬎ 100) ............. S66
`IV versus PO Iron Agents in the HD-CKD and PD-CKD Populations .......................... S67
`
`Table 13.
`
`Table 14.
`
`Table 15.
`
`Table 16.
`
`Table 17.
`
`Table 18.
`
`Table 19.
`
`Table 20.
`Table 21.
`Table 22.
`
`Table 23.
`Table 24.
`
`Table 25.
`Table 26.
`
`Table 30.
`
`Table 31.
`Table 31A.
`
`American Journal of Kidney Diseases, Vol 47, No 5, Suppl 3 (May), 2006: pp S1-S3
`
`S1
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`S2
`
`FIGURES
`
`Table 31B.
`Table 32.
`
`Table 33.
`Table 34.
`
`Table 35.
`Table 36.
`
`IV versus PO Iron Agents in the ND-CKD Population .................................................. S67
`RCTs Evaluating Effects of Treatment with IV L-Carnitine on Hb Levels and ESA
`Doses in the HD-CKD Population.................................................................................. S72
`Use of L-Carnitine as an Adjuvant to ESA Treatment in the HD-CKD Population.............. S73
`RCTs Evaluating Effects of Treatment With IV Ascorbic Acid on Hb Levels
`and ESA Doses in the HD-CKD Population ........................................................................... S74
`Use of Ascorbic Acid as an Adjuvant to ESA Treatments in the HD-CKD Population........ S74
`RCTs Evaluating Effects of Treatment With IM Androgens on Hb Levels in the
`HD-CKD Population ...................................................................................................... S75
`Use of Androgens as an Adjuvant to ESA Treatment in the HD-CKD Population......... S76
`Published Experience in Patients With Anemia, CKD, and a Preexisting
`Hematologic Disorder .................................................................................................... S84
`Hb Levels (g/dL) in Children Between 1 and 19 Years for Initiation of
`Anemia Workup.............................................................................................................. S88
`Hb Levels (g/dL) in Children Between Birth and 24 Months for Initiation
`of Anemia Workup.......................................................................................................... S88
`Literature Review of Anemia in Transplant CKD: Key Conclusions........................... S110
`Table 41.
`Prevalance of PTA by Duration of Posttransplantation Period ..................................... S112
`Table 42.
`Example of a Summary Table....................................................................................... S119
`Table 43.
`Systematic Review Topics and Screening Criteria ....................................................... S120
`Table 44.
`Literature Search Yield of Primary Articles for Systematic Review Topics................. S121
`Table 45.
`Table 45A. Assessment of Study Applicability............................................................................... S121
`Table 46.
`Details of First-Look Topics, Ovid Literature Searches, and Yield by Topic ............... S122
`Table 46A. Grades for Study Quality .............................................................................................. S122
`Table 47.
`Evaluation of Studies of Prevalence............................................................................. S123
`Table 48.
`Format for Guidelines................................................................................................... S123
`Table 49.
`Balance of Benefit and Harm ................................................................................................. S124
`Table 50.
`Definitions of Grades for Quality of Overall Evidence ................................................ S124
`Table 51.
`Example of an Evidence Profile ................................................................................... S125
`
`Table 37.
`Table 38.
`
`Table 39.
`
`Table 40.
`
`Figures
`
`Figure 1. Kidney Failure in the United States ................................................................................. S12
`Figure 2. Relationship Between Current and Previous Anemia Guidelines.................................... S14
`Figure 3. Relationship Between Hb Level and eGFR ..................................................................... S21
`Figure 4. Relationship Between eGFR and Prevalence of Anemia as Defined by Differing Hb
`Levels for (A) Males and (B) Females............................................................................. S21
`Prevalence of Anemia by CKD Stage .............................................................................. S22
`Figure 5.
`Figure 6. Relationship Between Level of Renal Function, Reflected by SCr Level or
`GFR, and Prevalence of Anemia, Defined at Different Hb Cutoff Levels, Among
`Patients under the Care of Physicians .............................................................................. S22
`Figure 7. Hb Percentiles by GFR in the Canadian Multicentre Longitudinal Cohort Study ........... S22
`Figure 8.
`Prevalence of Low Hb Level by Category of GFR in the Canadian Multicentre
`Longitudinal Cohort Study............................................................................................... S23
`Prevalence of Low Hb Level by eGFR in Patients with Diabetics Compared with the
`General Population ..................................................................................................................... S23
`Figure 10. Changes in Hb Levels and eGFR Over 2 years in Adult Patients with CKD Stages 3
`and 4 Not Treated with ESA ............................................................................................ S23
`Figure 11. Distribution of Hb Levels in Adult Males and Females by Age Group............................ S26
`Figure 12. Distribution of Ferritin and TSAT Values by Age Group in Males and Females ............. S30
`
`Figure 9.
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`FIGURES
`
`S3
`
`Figure 13. Distribution of Hb Levels by Ferritin Range in Patients with CKD ................................ S31
`Figure 14. Distribution of Hb Levels by TSAT Range in Patients with CKD................................... S31
`Figure 15. Target and Achieved Hb Levels in 18 RCTs Comparing Higher Against Lower
`(or Placebo/Control) Hb Targets for ESA Therapy .......................................................... S50
`Figure 16. Baseline Mean Pretreatment Hb Levels Compared with Achieved Mean Hb
`Levels in the Upper and Lower Target..................................................................... S51
`Figure 17. Exposure to Eprex® and Case Counts of PRCA .............................................................. S82
`Figure 18. Mean Epoetin Dose per Patient per Administration by Percentile of Dose (1st, 5th to
`95th, and 99th) ................................................................................................................. S82
`Figure 19. Process of Triaging a Topic to a Systematic Review or a Narrative Review ........................ S118
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`
`Acronyms and Abbreviations
`
`⌬ Change
`1 Increase
`2 Decrease
`ABP Ambulatory blood pressure
`ABPM Ambulatory blood pressure monitoring
`ACE Angiotensin-converting enzyme
`ADE Adverse drug event
`AE Adverse event
`ARBs Angiotensin receptor blockers
`ARF Acute renal failure
`AST Aspartate transaminase
`BID Twice daily
`BIW Twice weekly
`BP Blood pressure
`BSA Body surface area
`CABG Coronary artery bypass graft
`CBC Complete blood count
`CCr Creatinine clearance
`CESDS Center for Epidemiologic Studies Depression Scale
`CFU-E Erythroid colony-forming units
`CHF Congestive heart failure
`CHOIR Correction of Hemoglobin and Outcomes in Renal Insufficiency
`CHr Content of hemoglobin in reticulocytes
`CI Confidence interval
`CKD Chronic kidney disease
`CMV Cytomegalovirus
`CPG Clinical practice guideline
`CPR Clinical practice recommendation
`CREATE Cardiovascular Risk Reduction by Early Anemia Treatment With Epoetin Beta Trial
`CRI Corrected reticulocyte index
`CV Cardiovascular
`CVA Cerebrovascular accident
`CVD Cardiovascular disease
`D/C Discontinuation
`DBP Diastolic blood pressure
`DNA Deoxyribonucleic acid
`DOQI Dialysis Outcomes Quality Initiative
`EBPG European Best Practices Guideline
`eGFR Estimated glomerular filtration rate
`ERI Erythropoietin resistance index
`ERT Evidence Review Team
`ESA Erythropoiesis-stimulating agent
`ESRD End-stage renal disease
`FACIT Functional Assessment of Chronic Illness Therapy
`FDA Food and Drug Administration
`GFR Glomerular filtration rate
`GI Gastrointestinal
`Hb Hemoglobin
`Hct Hematocrit
`HD Hemodialysis
`
`S4
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`ACRONYMS AND ABBREVIATIONS
`
`S5
`
`HD-CKD Hemodialysis-dependent chronic kidney disease
`HDF Hemodiafiltration
`HPS Hemophagocytic syndrome
`HTN Hypertension
`HU Hydroxyurea
`HUI Health Utilities Index
`HUS Hemolytic uremic syndrome
`IHD Ischemic heart disease
`IM Intramuscular
`IU International Unit
`IV Intravenous
`KDIGO Kidney Disease: Improving Global Outcomes
`KDOQI Kidney Disease Outcomes Quality Initiative
`KDQ Kidney Disease Questionnaire
`KDQOL Kidney Disease Quality of Life
`KEEP Kidney Early Evaluation Program
`KLS Kidney Learning System
`KPS Karnofsky Performance Scale
`LV Left ventricular
`LVD Left ventricular dilation
`LVEDd Left ventricular end-diastolic diameter
`LVH Left ventricular hypertrophy
`LVMI Left ventricular mass index
`LVVI Left ventricular volume index
`MAP Mean arterial blood pressure
`MCH Mean corpuscular hemoglobin
`MCHC Mean corpuscular hemoglobin concentration
`MCV Mean corpuscular volume
`MDRD4 Modification of Diet in Renal Disease
`MI Myocardial infarction
`MR Mitral regurgitation
`N, n Number of subjects
`N/A Not applicable
`NAPRTCS North American Pediatric Renal Transplant Cooperative Study
`nd Not documented
`ND-CKD Non–dialysis-dependent chronic kidney disease
`NHANES National Health and Nutrition and Examination Survey
`NKF National Kidney Foundation
`NOS Not otherwise specified
`NS Not significant
`OR Odds ratio
`PD Peritoneal dialysis
`PD-CKD Peritoneal dialysis–dependent chronic kidney disease
`PHRBC Percent hypochromic red blood cells
`PHRC Percent hypochromic red cells
`PO Oral
`PRCA Pure red cell aplasia
`Pt
`Patient
`PTA Posttransplantation anemia
`QoAL Quality of American Life
`QOL Quality of life
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`S6
`
`ACRONYMS AND ABBREVIATIONS
`
`QOW Every other week
`RCT Randomized controlled trial
`rHuEPO Recombinant human erythropoietin
`RQoLP Renal Quality of Life Profile
`RR Relative risk
`SAE Severe adverse event
`SBP
`Systolic blood pressure
`SC Subcutaneous
`SCD Sudden cardiac death
`Serum creatinine
`SCr
`SF-36
`36-Item Medical Outcomes Study Short-Form Health Survey
`SIP
`Sickness Impact Profile
`SQUID Superconducting quantum interference device
`TDS Total daily supplement
`TID Thrice daily
`TIW Thrice weekly
`TRESAM Transplant European Survey on Anemia Management
`TSAT Transferrin saturation
`TTO Time trade-off
`TTP Thrombotic thrombocytopenic purpura
`Tx-ND-CKD Non–dialysis-dependent kidney transplant recipient population
`U Unit
`URR Urea reduction ratio
`USFDA United States Food and Drug Administration
`USRDS United States Renal Data System
`vs Versus
`WHO World Health Organization
`ZPP Zinc protoporphyrin
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`Anemia in Chronic Kidney Disease
`
`Work Group Membership
`
`Work Group Co-Chairs
`
`David B. Van Wyck, MD
`University of Arizona College of Medicine
`Tucson, AZ
`
`Kai-Uwe Eckardt, MD
`University of Erlangen-Nuremberg
`Erlangen, Germany
`
`John W. Adamson, MD
`Blood Center of SE Wisconsin
`Blood Research Institute
`Milwaukee, WI
`
`George R. Bailie, MSc, PharmD, PhD
`Albany College of Pharmacy
`Albany, NY
`
`Jeffrey S. Berns, MD
`University of Pennsylvania School of Medicine
`Philadelphia, PA
`
`Steven Fishbane, MD
`Winthrop University Hospital
`Mineola, NY
`
`Robert N. Foley, MD
`Nephrology Analytical Services
`Minneapolis, MN
`
`Sana Ghaddar, RD, PhD
`American University of Beirut
`Faculty of Agriculture and Food Sciences
`Beirut, Lebanon
`
`John S. Gill, MD, MS
`University Of British Columbia
`St. Paul’s Hospital
`Vancouver, Canada
`
`Kathy Jabs, MD
`Vanderbilt University Medical Center
`Nashville, TN
`
`Work Group
`
`Patricia Bargo McCarley, RN, MSN, NP
`Diablo Nephrology Medical Group
`Walnut Creek, CA
`
`Hans H. Messner, MD
`University Health Network
`Princess Margaret Hospital
`Toronto, Canada
`
`Allen R. Nissenson, MD
`UCLA Medical Center
`Los Angeles, CA
`
`Gregorio T. Obrador, MD
`Universidad Panamericana School of Medicine
`Mexico City, Mexico
`
`John C. Stivelman, MD
`Northwest Kidney Center
`Seattle, WA
`
`Colin T. White, MD
`British Columbia Children’s Hospital
`Vancouver, Canada
`
`Liaison Member
`Francesco Locatelli, MD
`Azienda Ospedaliera DI Lecco
`Lecco, Italy
`
`Iain C. Macdougall, MD
`King’s College Hospital
`London, England
`
`Evidence Review Team
`National Kidney Foundation Center for Guideline Development and Implementation at Tufts-New England
`Medical Center, Boston, MA
`
`Katrin Uhlig, MD, MS, Project Director and Program Director, Nephrology
`Christina Kwack Yuhan, MD, Assistant Project Director
`
`Amy Earley, BS
`Rebecca Persson, BA
`Gowri Raman, MD
`
`Ashish Mahajan, MD, MPH
`Priscilla Chew, MPH
`
`In addition, support and supervision was provided by:
`
`Joseph Lau, MD, Program Director, Evidence Based Medicine
`Ethan Balk, MD, MPH, Evidence Review Team Co-Director
`Andrew S. Levey, MD, Center Director
`
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`
`KDOQI Advisory Board Members
`
`Adeera Levin, MD, FACP
`KDOQI Chair
`Michael Rocco, MD, MSCE
`KDOQI Vice-Chair
`
`Garabed Eknoyan, MD
`KDOQI Co-Chair Emeritus
`
`Nathan Levin, MD, FACP
`KDOQI Co-Chair Emeritus
`
`George Bailie, PharmD, PhD
`Bryan Becker, MD
`Peter G. Blake, MD, FRCPC, MBB.Ch
`Allan Collins, MD, FACP
`Peter W. Crooks, MD
`William E. Haley, MD
`Alan R. Hull, MD
`Lawrence Hunsicker, MD
`Bertrand L. Jaber, MD
`Cynda Ann Johnson, MD, MBA
`George A. Kaysen, MD, PhD
`Karren King, MSW, ACSW, LCSW
`Michael Klag, MD, MPH
`Craig B. Langman, MD
`Derrick Latos, MD
`Donna Mapes, DNSc, MS
`Linda McCann, RD, LD, CSR
`Ravindra L. Mehta, MD, FACP
`Maureen Michael, BSN, MBA
`
`William Mitch, MD
`Joseph V. Nally, MD
`Gregorio Obrador, MD, MPH
`Rulan S. Parekh, MD, MS
`Thakor G. Patel, MD, MACP
`Brian J.G. Pereira, MD, DM
`Neil R. Powe, MD
`Claudio Ronco, MD
`Anton C. Schoolwerth, MD
`Raymond Vanholder, MD, PhD
`Nanette Kass Wenger, MD
`David Wheeler, MD, MRCP
`Winfred W. Williams, Jr., MD
`Shuin-Lin Yang, MD
`
`Ex-Officio
`Josephine Briggs, MD
`David Warnock, MD
`
`NKF-KDOQI Guideline Development Staff
`Anthony Gucciardo
`Kerry Willis, PhD
`
`Donna Fingerhut
`Margaret Fiorarancio
`Richard Milburn
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`
`VOL 47, NO 5, SUPPL 3, MAY 2006
`
`AJKD American Journal of
`
`Kidney Diseases
`
`Foreword
`
`This publication of the Clinical Practice
`
`Guidelines and Clinical Practice Recom-
`mendations for Anemia represents the second
`update of these guidelines since the first guide-
`line on this topic was published in 1997. The first
`set of guidelines established the importance of
`hemoglobin in dialysis patients, and established
`guidelines and targets for the treatment of ane-
`mia in dialysis patients. The first update, pub-
`lished in 2000, described anemia in a wider
`spectrum of the chronic kidney patients, and
`included those not on dialysis.
`A number of important randomized clinical
`trials and large observational studies have been
`commenced or completed in CKD populations
`both on and off dialysis, over the past 5 years.
`The key questions that have been addressed in
`these recent studies have been the optimal
`hemoglobin target for CKD patients. To date
`there has been little support normalizing hemo-
`globin, though a number of important studies
`have not been completed or reported (CHOIR
`and TREAT), and the community eagerly awaits
`them. Nonetheless, the key aspects of the pub-
`lished data from both controlled trials and
`observational studies, support the ongoing im-
`portance of hemoglobin levels in risk stratifica-
`tion of patients with CKD, whether with native
`or transplant kidneys, or on dialysis therapies.
`Much has been learned about the causes of
`erythropoietin resistance, and some small stud-
`ies have reported methods of treating ESA
`resistance. Furthermore, there are multiple new
`insights into the optimizing treatment of ane-
`mia with iron supplementation and ESA. Novel
`actions of ESAs on cognitive function, as well
`as preservation of kidney and cardiac function
`have been described. To date there are no
`clinical trials to support the use of ESA for
`
`these ‘non anemia’ purposes, but both the
`basic and clinical science of ESA therapy are
`advancing at a rapid pace.
`This updated set of guidelines on anemia is
`unique and different from the previous anemia
`guidelines. Firstly, the guidelines have been sepa-
`rated into evidence based guidelines and clinical
`practice recommendations, based on the strength
`of evidence. The term guideline is reserved for
`that which is robust enough to be used, if appro-
`priate, as a clinical performance measure. Clini-
`cal practice recommendations are those recom-
`mendations based on expert opinion of the
`working group, but lacking sufficient hard data;
`CPRs are also susceptible to testing in a clinical
`trial. Secondly, these guidelines incorporated in-
`dividuals from countries outside the US (Europe,
`UK, Middle East, Mexico and Canada) and at-
`tempted to build on most recently published
`European Best Practice guidelines (2004), as
`well as the previously published KDOQI ver-
`sions. Lastly, the working group was clearly
`focused on ensuring that
`this document was
`robust and clear for the reader. There was an
`overt recognition that research recommendations
`should be organized and described in sufficient
`detail to ensure that prior to the next update of
`any anemia guideline, there would be new data
`addressing gaps in our current knowledge. Thus,
`there are no concrete research recommendations
`in this version;
`they will be published in a
`separate document in the near future. The in-
`tended effect of this change in how the research
`recommendations are presented is to provide a
`
`© 2006 by the National Kidney Foundation, Inc.
`0272-6386/06/4705-0101$32.00/0
`doi:10.1053/j.ajkd.2006.04.023
`
`American Journal of Kidney Diseases, Vol 47, No 5, Suppl 3 (May), 2006: pp S9-S10
`
`S9
`
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`

`
`S10
`
`FOREWORD
`
`guidepost for funding agencies and investigators
`to target research efforts in those areas that will
`provide important information that will benefit
`patient outcomes.
`This final version of the Clinical Practice
`Guidelines and Recommendations for Anemia
`has undergone revision in response to comments
`during the public review, an important and inte-
`gral part of the KDOQI guideline process. None-
`theless, as with all guideline documents, there is
`a need for revision in the light of new evidence,
`and more importantly, a concerted effort to trans-
`late the guidelines into practice. Considerable
`effort has gone into their preparation over the
`past 2 years, and every attention has been paid to
`their detail and scientific rigor, no set of guide-
`lines and clinical practice recommendations, no
`matter how well developed, achieves its purpose
`unless it is implemented and translated into clini-
`cal practice. Implementation is an integral com-
`ponent of the KDOQI process, and accounts for
`the success of its past guidelines. The Kidney
`
`Learning System (KLS) component of the Na-
`tional Kidney Foundation is developing imple-
`mentation tools that will be essential
`to the
`success of these guidelines.
`In a voluntary and multidisciplinary undertak-
`ing of this magnitude, many individuals make
`contributions to the final product now in your
`hands. It is impossible to acknowledge them
`individually here, but to each and every one of
`them we extend our sincerest appreciation. This
`limitation notwithstanding a special debt of grati-
`tude is due to the members of the Work Group,
`and their co-chairs, David Van Wyck and Kai-
`Uwe Eckardt. It is their commitment and dedica-
`tion to the KDOQI process that has made this
`document possible.
`
`Adeera Levin, MD
`KDOQI Chair
`
`Michael Rocco, MD
`KDOQI Vice-Chair
`
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`EXECUTIVE SUMMARY
`
`INTRODUCTION
`Anemia commonly contributes to poor qual-
`ity of life (QOL) in patients with chronic
`kidney disease (CKD). Fortunately, among the
`disorders that may afflict patients with CKD,
`anemia is perhaps the most responsive to treat-
`ment. Anemia was the subject of one of the
`first efforts of the National Kidney Foundation
`(NKF) to improve patient outcomes through
`the development, dissemination, and implemen-
`tation of Dialysis Outcomes Quality Initiative
`(DOQI) Clinical Practice Guidelines.1 The first
`update of these guidelines appeared in 2001
`under the newly organized NKF-Kidney Dis-
`ease Outcomes Quality Initiative (KDOQI).2
`In 2004, the NKF-KDOQI Steering Committee
`appointed a Work Group and Evidence Review
`Team (ERT) to undertake the first comprehen-
`sive revision of the KDOQI Cl