Timing and Determinants of Erythropoietin Deficiency in Chronic Kidney Disease

Background and objectives Anemia in patients with CKD is highly related to impaired erythropoietin (EPO) response, the timing and determinants of which remain unknown. Design, setting, participants, & measurements This study measured EPO levels and studied their relation to GFR measured by 51Cr-EDTA renal clearance (mGFR) in 336 all-stage C.KD patients not receiving any erythropoiesis-stimulating agent. Results In patients with anemia defined by World Health Organization criteria (hemoglobin [Hb] <13 g/dl in men and 12 g/dl in women), EPO response to Hb level varied by mGFR level. EPO and Hb levels were negatively correlated (r=-0.22, P=0.04) when mGER was >30 ml/min per 1.73 m(2), whereas they were not correlated when mGER was <30 (r=0.09, P=0.3; P for interaction=0.01). In patients with anemia, the ratio of observed EPO to the level predicted by the equation for their lib level decreased from 0.72 (interquartile range, 0.57-0.95) for mGFR >= 60 ml/min per 1.73 m(2) to 0.36 (interquartile range, 0.16-0.69) for mGFR <15. Obesity, diabetes with nephropathy other than diabetic glomerulopathy, absolute iron deficiency, and high C-reactive protein concentrations were associated with increased EPO levels, independent of Hb and mGER. Conclusions Anemia in CKID is marked by an early relative EPO deficiency, but several factors besides Hb may persistently stimulate EPO synthesis. Although EPO deficiency is likely the main determinant of anemia in patients with advanced CKD, the presence of anemia in those with mGER >30 ml/min per 1.73 m(2) calls for other explanatory factors. Clin J Am Soc Nephrol 7: 35-42,2012. doi: 10.2215/CJN.04690511