Lessons from clinical trials with erythropoiesis-stimulating agents (ESAs)

Abstract

Initially, the optimal degree of anemia correction in patients with chronic kidney disease by erythropoiesis-stimulating agents (ESAs) relied mainly on the results of observational studies. Many of these studies supported full anemia correction. Subsequently, randomized controlled trials of small sample size examined intermediate outcomes, but only trials with hard outcomes could settle this issue convincingly. In contrast to expectations based on epidemiological studies, the randomized controlled trials of large sample size performed in patients with chronic kidney disease in the last two decades have convincingly shown that full anemia correction, as compared to partial anemia correction, is associated with increased risk of adverse events and mortality and that the increased risk outweighs potential benefit. Although transfusion needs decrease and quality of life increases with actively raised hemoglobin levels in severely anemic patients with chronic kidney disease, any benefit of increasing hemoglobin levels above 11.5 g/dL is at best unclear at present. As some of these patients may experience improvement in physical and mental health and overall well-being above this level, individualization of therapy may be chosen in those who are prepared to accept the associated risks. Future, adequately powered, and blinded randomized controlled trials of anemia treatment using patient-reported outcomes as primary rather than secondary endpoints are needed to answer the question of the optimal hemoglobin target as regards the quality of life.