Anemia in chronic kidney disease

Abstract

Anemia is common and associated with adverse outcomes in children with chronic kidney disease (CKD). Many factors contribute to declining hemoglobin as CKD progresses, but impaired production of erythropoietin by failing kidneys is a central cause. Hepcidin-mediated iron restriction also contributes to anemia by downregulating both intestinal iron absorption and release of stored iron for erythropoiesis. The core components of anemia management remain erythropoiesis-stimulating agents (ESA) and iron supplementation, but despite these therapies, a substantial number of children remain anemic. Although escalating ESA dose to target higher hemoglobin has been associated with adverse outcomes in adults, no trials have investigated this association in children, and maintaining hemoglobin levels in a narrow range with conservative ESA dosing is challenging. Judicious use of iron supplementation can enhance the response to ESAs, but the iron storage markers most commonly used in clinical practice have limitations in distinguishing which patients will benefit most from additional iron. Several novel anemia therapies, including hypoxia-inducible factor stabilizers, prolyl hydroxylase inhibitors, and dialysate-delivered iron supplements, have been developed and may offer options for alternative anemia management. However, the safety and efficacy of these agents in children with CKD has yet to be assessed.

Keywords: Anemia; Erythropoiesis-stimulating agent; Hemoglobin; Hepcidin; Iron-restricted erythropoiesis.