Endogenous Erythropoietin and the Association with Inflammation and Mortality in Diabetic Chronic Kidney Disease

Background and objectives Anemia and inflammation are prevalent in diabetic patients with chronic kidney disease (CKD). The role of endogenous erythropoietin (EPO) in the pathophysiology of anemia in chronic diseases and its relationship to clinical outcomes remain uncertain. In this cohort study, we aimed to identify factors associated with endogenous EPO levels and investigate their relation to all-cause mortality. Design, setting, participants, & measurements Between 2004 and 2005, 215 patients with type 2 diabetes were enrolled. Exclusion criteria included stage renal disease ESRD and any form of anemia therapy. The association of EPO levels with clinical and laboratory variables was investigated by linear regression modeling. Predictors of all-cause mortality were evaluated by Cox proportional hazards analyses. Results Patients (median age, 67 years; 52% men; median duration of diabetes, 10 years; median estimated GFR, 49 ml/min per 1.73 m(2)) were followed for up to 7.0 years. Forty-one patients died. Elevated EPO levels were independently associated with elevated C-reactive protein, low ferritin, and hypertension, in a multivariate model that also included age, cardiovascular disease, kidney function, albumin, cholesterol, and hemoglobin. Higher EPO levels were independently predictive for mortality, as were age, low levels of albumin, and cardiovascular disease. Conclusions In diabetic patients with CKD, elevated endogenous EPO levels were predictive for mortality and were related mainly to markers of inflammation, independent of kidney function, and despite low hemoglobin levels. Understanding the phenomenon of EPO resistance and iron dysregulation caused by inflammation is crucial for effective and safe treatment of anemia in patients with CKD. Clin J Am Soc Nephrol 6: 1573-1579, 2011. doi: 10.2215/CJN.00380111