Clinical Practice Guidelines for Anemia in Chronic Kidney Disease: Problems and Solutions. A Position Statement From KDIGO

Francesco Locatelli; Allen R. Nissenson; Brendan J. Barrett; Rowan G. Walker; David C. Wheeler; Kai U. Eckardt; Norbert H. Lameire; Garabed Eknoyan


Kidney Int. 2008;74(10):1237–1240 

In This Article

Abstract and Introduction


The development of clinical practice guidelines for the treatment of anemia in chronic kidney disease has been instrumental in identifying and reducing variations in the use of erythropoiesis-stimulating agents and iron replacement. Challenges to the effectiveness and safety of recommendations made in these guidelines were magnified when recent clinical trials showed no benefit or harm with respect to cardiovascular outcomes in subjects randomized to higher target hemoglobin levels. To address these concerns, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international conference to examine the problems and shortcomings of existing anemia guidelines, which are a prime example of duplication of efforts to derive recommendations from a limited evidence base. The meeting was attended by representatives of the major guideline developing organizations, who agreed to avoid future duplicative efforts and to save resources in generating a common evidence report, whose recommendations could then be prioritized and implemented locally. This is a report to the international nephrology community of the recommendations for and timeline of the next anemia guidelines. It has been reviewed by the conference participants and approved as a position statement by the KDIGO Board of Directors.


The introduction of erythropoietin into clinical practice in 1989 has been associated with controversies and concerns, which remain after almost two decades of investigation and practical experience. When to start, how to use, what targets to achieve, and what outcomes to assess are but some of the questions that persist in the management of anemia in dialysis patients. The debate expanded when the use of erythropoietin was extended into the treatment of anemia in earlier stages of chronic kidney disease (CKD), before the need for dialysis. The publication of clinical practice guidelines on the management of anemia in CKD by several organizations has been instrumental in reducing the wide variations in practice that followed the initial use of erythropoietin. The gaps in knowledge identified in these guidelines have provided a basis for much of the research that has been published on the subject since that time.

An upper limit of the targeted hemoglobin level was a component of the initial guidelines[1] because of the Normal Hematocrit Cardiac Trial published in 1998,[2] which suggested that attempts to normalize hematocrit in hemodialysis patients was associated with harm. The upper limit for targeted hemoglobin was liberalized in the course of updating the original guidelines because of observational studies showing a reduction in hospitalization, morbidity, and mortality at higher achieved levels of hemoglobin.[3,4,5] Nevertheless, concerns remained because of the limited available data on the effectiveness, efficacy, and safety of the recommended targets, especially when complete correction of anemia did not lead to an associated improvement in the left ventricular mass.[6] These concerns were magnified when two large clinical trials in patients with CKD stages 3 and 4 (CHOIR and CREATE) were published in November 2006 showing no benefit in one (CREATE) and harm in the other (CHOIR) with respect to cardiovascular outcomes in subjects randomized to a higher target hemoglobin level.[7,8] The subsequent debate extended beyond the medical literature, entailed regulatory agencies, and challenged the existing guidelines that were, in fact, the catalysts that prompted some of the very clinical trials that initiated the controversy.[9]

To address these issues, Kidney Disease Outcomes Quality Initiative (KDOQI), which had released its updated anemia guidelines in 2006 prior to the new data being published, reconvened a workgroup to review these and other newer studies. After thorough assessment of all the available evidence, including the recently published trials, KDOQI published revised recommendations for the target hemoglobin level in CKD patients in September 2007.[10]

At the same time, KDIGO convened a meeting in October 2007 to review anemia management in CKD patients and to develop recommendations for future guidelines in this field. This report presents the deliberations and recommendations of the meeting. It has been reviewed by the conference participants and adopted as a position statement by the KDIGO Board of Directors.


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