Factors Contributing to Erythropoietin Hyporesponsiveness Among Hemodialysis Patients: A Cross-Sectional Multicenter Study

Background Anemia resistant to erythropoietin stimulating agents (ESAs) is a risk factor for all-cause mortality. Determining the etiologies of hyporesponsiveness may help overcome the resistance. We investigated the contributing factors in a population of hemodialysis patients. Methods In a multicenter cross-sectional study, from January 2015 to May 2015, point-prevalent hemodialysis patients from 22 dialysis centers in Tehran, Iran, were enrolled. Demographic, clinical, and laboratory data and drug history were recorded. ESA hyporesponsiveness index (EHRI) was calculated by dividing weekly ESA dose per kilogram of body weight (IU/Kg/W) by hemoglobin level (g/dL). Patients with EHRI ≥ 16.49 (4^th quartile) were compared with those with EHRI < 16.49 with respect to influential factors. Results A total of 1224 patients were enrolled among whom, 306 (25%) had an EHRI ≥ 16.49 with a mean hemoglobin level of 9.8 ± 1.4 g/dL. There was no age, gender, or dialysis vintage difference within the groups. Iron status, parathormone, CRP, and diabetes were also similar. Hyporesponsive patients had lower body mass index (BMI) and lower serum albumin (P < 0.05). The proportion of patients who were treated with angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) were significantly higher (P < 0.01) in hyporesponsive patients. In multivariate analysis, high doses of Venofer, high Kt/V, and high phosphate level were independently related to the presence of EHRI, and treatment with ACE/ARB was a marginally significant factor for EPO resistance. Conclusions Apart from the most validated parameters responsible for ESA hyporesponsiveness (e.g. Iron deficiency, dialysis inadequacy, and poorly controlled serum phosphate level), other potential risk factors such as treatment with ACEi/ARB should be evaluated. Discontinuation of these drugs might be a therapeutic strategy to overcome ESA resistance.