Should the target hemoglobin for patients with chronic kidney disease treated with erythropoietic replacement therapy be changed?

Recombinant human erythropoietin (rHuEPO, epoetin) revolutionized the treatment of anemia in patients with chronic kidney disease (CKD) when it was approved for use in the United States in 1989. Among dialysis patients, the mean hemoglobin (Hb) in patients undergoing dialysis rose from 7-8 g/dl prior to 1989 to 11-12 g/dl today. Among patients with CKD not on dialysis, epoetin use has not been as broadly applied as among dialysis patients, and although the mean Hb level in this patient population has increased, the impact has been less than in patients on dialysis. The optimal treatment target for epoetin remains controversial. Consistent with clinical practice guidelines, current practice in dialysis patients in the United States aims to maintain a target Hb of 11-12 g/dl, a level that is still well below the normal range. Debate centers on whether the current Hb target is too low and whether the target range is too narrow. Quality of life clearly improves in many individuals as Hb rises into the normal range from lower levels. In retrospective studies, higher Hb levels have been associated with lower risks of hospitalization and mortality. However, one large, prospective clinical trial has raised concern about normalizing Hb in hemodialysis patients with cardiac disease, and other prospective studies have not yet provided convincing evidence of significant benefits from normalizing Hb in dialysis-dependent and non-dialysis-dependent patients with CKD. A relative lack of information on non-dialysis-dependent patients with CKD and changes in fiscal policies regulating reimbursement for epoetin have contributed to uncertainty as to the best practices for anemia management in patients with CKD. There is increasing interest in the potential benefits of broadening the current target Hb range or eliminating an upper limit altogether and instead establishing a minimum Hb goal. While some extension of the upper limit of the currently recommended target Hb range might appear to be reasonable, the extent to which this should be extended, the benefits, risks, and costs of maintaining higher Hb levels in patients with CKD, and whether target Hb levels should be different in different CKD patient groups remains to be determined. Future efforts are likely to focus on selecting patient populations most likely to benefit from normalizing Hb, while adjusting the range of a subnormal Hb target for others.