Mechanisms of anemia in CKD

Abstract

Anemia is a common feature of CKD associated with poor outcomes. The current management of patients with anemia in CKD is controversial, with recent clinical trials demonstrating increased morbidity and mortality related to erythropoiesis stimulating agents. Here, we examine recent insights into the molecular mechanisms underlying anemia of CKD. These insights hold promise for the development of new diagnostic tests and therapies that directly target the pathophysiologic processes underlying this form of anemia.

Figure 1.

Schematic representation of the mechanisms underlying anemia of CKD. Iron and EPO are crucial for red blood cell production in the bone marrow. Iron availability is controlled by the liver hormone hepcidin, which regulates dietary iron absorption and macrophage iron recycling from senescent red blood cells. There are several feedback loops that control hepcidin levels, including iron and EPO. In CKD patients (particularly in end stage kidney disease patients on hemodialysis), hepcidin levels have been found to be highly elevated, presumably due to reduced renal clearance and induction by inflammation, leading to iron-restricted erythropoiesis. CKD also inhibits EPO production by the kidney, and may also lead to circulating uremic-induced inhibitors of erythropoiesis, shortened red blood cell lifespan, and increased blood loss. Black and gray arrows represent normal physiology (black for iron and hormonal fluxes, gray for regulatory processes). Colored arrows represent the additional effects of CKD (blue for activation, red for inhibition). RBC, red blood cell.