Characterization of chronic and acute ESA hyporesponse: a retrospective cohort study of hemodialysis patients

摘要

Background Some patients with chronic kidney disease do not respond adequately to erythropoiesis-stimulating agent (ESA) treatment; these patients are referred to as ESA hyporesponders. There is no widely accepted contemporary definition for chronic ESA hyporesponse. The study objective was to propose and validate an operational definition for chronic ESA hyporesponse. Methods This was a retrospective cohort study using electronic health care records. Participants were anemic hemodialysis patients treated during February 2012 and were followed for 15?months. Patients’ ESA response (responders) or lack of response (chronic and acute hyporesponders) based on longitudinal patterns of ESA dose and hemoglobin level was assessed. Persistence of hyporesponse, longitudinal iron measures, transfusion rates, and mortality rates were analyzed. Frequency of blood transfusions (monthly) and death rates (quarterly) were calculated. Log normalized serum ferritin concentration was analyzed. Results Of 97,677 eligible patients, 6632 had acute hyporesponsiveness (ESA responsiveness restituted in?≤?4?months) and 3086 had chronic hyporesponsiveness (lack of ESA response for?>?4?months). Over months 1–4 among chronic hyporesponders, mean serum ferritin (722–785?ng/mL) and transferrin saturation (TSAT; 26.76?%-27.08?%) were constant, while acute hyporesponsive patients experienced increased ferritin (654-760?ng/mL) and TSAT (25.71–30.88?%) levels. Compared to ESA responders (0.19–0.30?%), chronic hyporesponders were transfused 7-times (1.20–2.17?%) more frequently over follow-up. Quarterly mortality was greatest in chronic ESA hyporesponders (2.98–5.48?%), followed by acute ESA hyporesponders (2.17–3.30?%) and ESA responders (1.43–2.49?%). With consistence over the study, chronic hyporesponders died more frequently than patients in the other study cohorts. Conclusions Findings indicate that 4?months of continuous ESA hyporesponsiveness can be used to differentiate acute from chronic hyporesponsiveness. This definition of chronic hyporesponsiveness is supported by outcome data showing higher mortality and transfusion rates in chronic hyporesponders compared to acute hyporesponders.