ESAs in Dialysis Patients

Abstract

The philosopher Isaiah Berlin1 divides authors and perhaps people in general into two categories: Hedgehogs, who view the world through the lens of one defining idea, and foxes, for whom the world cannot be boiled down to a single idea. Looking at erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in chronic kidney disease (CKD), should there be a single conclusion about the safety of ESAs? In a previous editorial, I discussed the use of ESAs in nondialysis patients.2 Here, I consider their continued use for the anemia of dialysis patients. ESAs have proved effective in correcting anemia in patients with ESRD. No one relishes blithely turning the clock back to the pre-ESA era, when dialysis patients were treated with repeated blood transfusions, iron therapy, anabolic steroids, and other maneuvers; however, mortality and the rate of cardiovascular complications in the dialysis population remain high, and reducing risk would be important in improving outcomes. Randomized, controlled trials (RCTs) demonstrate there is increased risk in correcting anemia with ESAs in all patients with CKD–both dialysis and nondialysis. In the recently published Trial to Reduce Cardiovascular Endpoints with Aranesp Therapy (TREAT),3 a placebo-controlled, double-blind, randomized study comprising 4038 nondialysis patients, there was a significantly higher rate of strokes in patients who were treated with darbepoetin (hazard ratio 1.92; P < 0.001) as well as higher rates of thromboembolism and cancer-related deaths. In the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) study,4 the risk was a higher rate of mortality and cardiovascular complications in nondialysis patients targeted to a hemoglobin (Hb) level of 13.0 g/dl with epoetin-alfa (hazard ratio 1.34; P = 0.03). A higher rate of death or myocardial infarction (MI) or vascular access thrombosis was also observed in the Normal Hematocrit study.5 Meta-analyses have reached …