Pharmacologic Adjuvants to Reduce Erythropoietin Therapy Dose in Anemia of Chronic Kidney Disease and End Stage Renal Disease

Anemia is one of the leading causes of morbidity in chronic renal failure.1 Chronic kidney disease (CKD) associated anemia is largely due to reduced erythropoietin (EPO) release and, to a lesser degree, to shortened red cell survival.2 To overcome EPO deficiency in this population, the development and administration of erythropoiesis-stimulating agents (ESAs) such as recombinant human EPO and darbepoetin alfa (DPO) has resulted in substantial health benefits, including improved quality of life, reduced blood transfusion requirements, decreased left ventricular mass, diminished sleep disturbance and enhanced exercise capacity.1-7 Unfortunately in recent clinical trials, a proportion of patients exhibited complications such as fatal or nonfatal stroke, access thrombosis, increase in thrombotic events and exacerbation of malignancy associated with overly aggressive correction of anemia. 8-10 It is not established whether these complications are related to higher dose of EPO, underlying EPO resistance factors (i.e. inflammation) or achieving higher hematocrit (HCT). A multifactorial combination of predisposing circumstances is possible. A number of pharmacologic agents have been evaluated as adjuvant to ESAs therapy. These agents include iron, L-carnitine, ascorbic acid, androgens, statins, pentoxifylline and Nacetylcysteine. In this review article we will focus on the agents that have been used in conjunction with EPO to correct anemia in patient with chronic kidney disease and endstage renal disease in an effort to reduce the dose requirement of EPO.