Confusion about the appropriate use of erythropoiesis-stimulating agents in patients undergoing maintenance dialysis.

The introduction of recombinant erythropoietin for clinical use in dialysis patients in 1989 was considered a major milestone for the long-term treatment of these vulnerable patients. It was assumed that increasing hemoglobin concentrations would not only improve patient-reported outcomes, as shown in early trials, but also reduce morbidity and mortality. Evidence that has accumulated over the ensuing two decades has repeatedly contradicted this assumption. The presence of powerful stake holders, strong competing incentives, strong prior beliefs, and scarce and confusing evidence have maintained uncertainty about the appropriate treatment of patients with chronic kidney disease who are anemic, including those requiring dialysis. This commentary recalls the decades-long scientific and regulatory journey and attempts to make the case for the urgent need for potentially paradigm-shifting evidence generation to identify the therapeutic sweet spot that would maximize net benefits of treatment with erythropoiesis-stimulating agents in patients undergoing dialysis.