Predictors of erythropoietin response in nondiabetic end-stage renal-disease patients on hemodialysis

Abstract

Background Erythropoietin (EPO) resistance is an essential health problem in end-stage renal-disease patients as it is associated with increased mortality. Despite combined intravenous iron usage, anemia exists substantially in the majority of patients, indicating the presence of other pathophysiological mechanisms such as inflammation that could lead to EPO resistance. Objectives To evaluate neutrophil-lymphocytic ratio (NLR) and platelet-lymphocytic ratio (PLR) as possible predictors of EPO resistance in nondiabetic patients on hemodialysis (HD). Patients and methods Fifty patients aged from 18 to 70 years old were diagnosed as end-stage renal disease and on HD regularly for more than 6 months and are receiving EPO therapy for at least more than 2 months. EPO dosing and intravenous iron supplementations given to HD patients and response assessment were following the 2012 Kidney Disease Improving Global Outcome guidelines. EPO resistance was assessed using EPO-stimulating agent (ESA) hyporesponsiveness index (EHRI), calculated as EPO weekly dose divided by body weight (kg) divided by hemoglobin level (Hb) and correlation with NLR, PLR, and C-reactive protein (CRP) was analyzed. EPO hyporesponsiveness (nonresponders) was diagnosed when we need to increase ESA doses up to 50% higher than the dose at which they were stable to maintain a steady Hb concentration after the first month of EPO treatment on weight-based dosing or after treatment with continuous EPO doses. Results Nonresponders to EPO had significantly higher EHRI, NLR, PLR, and CRP in comparison with responders. EHRI had a weak positive correlation with NLR (r = 0.18, P = 0.20), whereas it had a strong positive correlation with PLR (r = 0.65, P = 0.001). PLR at the cutoff point <116.5 has 90% sensitivity and 70% specificity for prediction of response to EPO therapy with overall accuracy that was 82% (area under curve [AUC]=0.79). Conclusion Inflammation is a major contributor in EPO resistance. CRP and PLR could represent cheap and simple parameters to predict response to EPO therapy in nondiabetic HD patients.