Endogenous plasma erythropoietin, cardiovascular mortality and all-cause mortality in renal transplant recipients

Cardiovascular disease (CVD) is the main cause of mortality in renal transplant recipients (RTR). Classical factors only partly explain the excess risk. We hypothesized that high EPO-a marker for inflammation, angiogenesis and hypoxia-is associated with CVD in RTR. A total of 568 RTR (51 +/- 12 years; 45% female; creatinine clearance (CrCl) 57 +/- 20 mL/min/1.73 m(2)) were included at median 6 [IQR 311] years after transplantation. Subjects on exogenous EPO and ferritin-depleted subjects were excluded. Median EPO level was 17.3 [IQR 11.9-24.2] IU/L. Gender-stratified tertiles of age-corrected EPO were positively associated with waist circumference (but not BMI), CVD history, time since transplantation, diuretics, azathioprine, CRP, mean corpuscular volume and triglyceride levels, and inversely with CrCl, RAAS-inhibition, cyclosporine, hemoglobin, total- and HDL-cholesterol. During follow-up for 7 [6-7] years, 121 RTR (21%) died, 64 of cardiovascular (CV) causes. Higher EPO (per 10 IU/L) was associated with total (HR1.16 [1.04-1.29], p = 0.01) and CV mortality (HR1.22 [1.06-1.40], p = 0.005), independent of age, gender, hemoglobin, inflammation, renal function and Framingham risk factors. Thus, EPO and mortality are linked in RTR, independent of potential confounders. This suggests that yet other mechanisms are involved. Dissecting determinants of EPO in RTR may improve understanding of mechanisms behind excess CV risk in this population.