Uremic Toxins Affect Erythropoiesis during the Course of Chronic Kidney Disease: A Review

Chronic kidney disease (CKD) is a global health problem characterized by progressive kidney failure due to uremic toxicity and the complications that arise from it. Anemia consecutive to CKD is one of its most common complications affecting nearly all patients with end-stage renal disease. Anemia is a potential cause of cardiovascular disease, faster deterioration of renal failure and mortality. Erythropoietin (produced by the kidney) and iron (provided from recycled senescent red cells) deficiencies are the main reasons that contribute to CKD-associated anemia. Indeed, accumulation of uremic toxins in blood impairs erythropoietin synthesis, compromising the growth and differentiation of red blood cells in the bone marrow, leading to a subsequent impairment of erythropoiesis. In this review, we mainly focus on the most representative uremic toxins and their effects on the molecular mechanisms underlying anemia of CKD that have been studied so far. Understanding molecular mechanisms leading to anemia due to uremic toxins could lead to the development of new treatments that will specifically target the pathophysiologic processes of anemia consecutive to CKD, such as the newly marketed erythropoiesis-stimulating agents.