Epoetin alfa resistance in hemodialysis patients with chronic kidney disease: a longitudinal study

Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.