Anemia of chronic kidney disease.

A nemia is a common complication in patients with chronic kidney disease (CKD). Recombinant erythropoietin (epoetin) has been the most important advance in treating this anemia. Erythropoietin was approved by the Food and Drug Administration (FDA) in 1989. Although the initial goal of treating CKD anemia with epoetin was to prevent blood transfusions, evidence from prospective studies also demonstrated marked attenuation in the symptoms of anemia (1–3). Subsequently, several observational studies have demonstrated associations between anemia and harder outcomes, such as mortality and cardiovascular complications (4– 6). Likewise, studies have documented an association between the severity of anemia and left ventricular hypertrophy (LVH) (7,8). By the early to mid-1990s, the majority of dialysis and non-dialysis CKD patients and many patients without CKD were receiving epoetin therapy. The benefits of epoetin therapy resonated among patients and providers alike: Preventing blood transfusions, improving quality of life, improving survival, and reducing cardiovascular complications including heart failure and LVH. Between 1991 and 2005, the target and achieved levels of hemoglobin (Hb) increased, with mean Hb in hemodialysis patients being raised from 9.7 to 12 g/dl (9). The publication of the Normal Hematocrit study in 1998 (10) and more recently the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) (11) and Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin (CREATE) (12) studies have precipitated FDA advisories (13) about achieving a Hb in the 10to 12-g/dl range. A narrow Hb target range and the observation that Hb varies in the majority of patients with CKD make treating anemia quite challenging. The reports of pure red cell aplasia (PRCA) from neutralizing antierythropoietin antibodies has also generated considerable concern about the safety of epoetin. Finally, despite ongoing worries about epoetin therapy, newer erythropoiesis-stimulating agents (ESA) have emerged. This issue of CJASN contains three articles on various aspects of epoetin therapy and anemia management in patients with CKD. Two of these are mini-reviews, and one is an original article. Newer ESA The market opportunity for the pharmaceutical industry from epoetin has not gone unnoticed to the pharmaceutical world. An estimated $22 billion worth of Epogen has been sold (14). A derivative of epoetin, darbepoetin, has also been a success. More recently, Continuous Erythropoiesis Receptor Activator (CERA), a derivative of epoetin, has been approved by the FDA. Epoetin is now Medicare’s largest single pharmaceutical expense, costing approximately $2 billion in 2005 (15). Several companies have or are developing ESA. In this issue of CJASN, Macdougall (16) reviews the recent progress in developing epoetin analogues or derivatives.