Causes of Anemia in Chronic Kidney Disease

 A common complication of chronic kidney disease(CKD) is anemia. Anemia in CKD is typically normocytic, normochromic, and hypoproliferative. The most known cause is the decreased production of Erythropoietin by the damaged kidney. Aside from EPO deficiency, what else contributes to the anemia of CKD? Numerous studies suggest that circulating uremic-induced inhibitors of erythropoiesis contribute to the anemia. Shortened red blood cell survival also contributes, as demonstrated by radioisotope labeling studies. Nutritional deficiencies, such as folate and vitamin B12, due to anorexia or dialysis losses are currently  not common with the routine use of supplementation in hemodialysis patients.

CKD patients have increased iron losses, estimated at 1–3 g per year in hemodialysis patients, due to chronic bleeding from uremia-associated platelet dysfunction, frequent phlebotomy, and blood trapping in the dialysis apparatus. CKD patients also have impaired dietary iron absorption. Intravenous iron is preferred for hemodialysis patients because of impaired dietary iron absorption.

In addition to true iron deficiency, many CKD patients have functional iron deficiency, characterized by impaired iron release from body stores that is unable to meet the demand for erythropoiesis (also called reticuloendothelial cell iron blockade). These patients have low serum transferrin saturation (a measure of circulating iron) and normal or high serum ferritin (a marker of body iron stores).

Recent studies suggest that hepcidin excess may account for the impaired dietary iron absorption and reticuloendothelial cell iron blockade present in many CKD patients.  Hepcidin is the main hormone responsible for maintaining systemic iron homeostasis. Produced by the liver and secreted into circulation,hepcidin binds and induces degradation of the iron exporter, ferroportin, on duodenal enterocytes, reticuloendothelial macrophages, and hepatocytes to inhibit iron entry into the plasma. Inflammatory cytokines directly induce hepcidin transcription, presumably as a mechanism to sequester iron from invading pathogens, leading to the iron sequestration, hypoferremia, and anemia that are hallmarks of many chronic diseases including CKD.

In summary, anemia of CKD is a multifactorial process due to:

1.Relative EPO deficiency 

2.Uremic-induced inhibitors of erythropoiesis 

3.Shortened erythrocyte survival

4.Disordered iron homeostasis due to hepcidin excess

5.Impaired iron absorption

6.Blood loss due to uremia induced platelet dysfunction