Abstract
BackgroundSome 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.MethodsThis 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.ResultsOf 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.ConclusionsFindings 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0138-x) contains supplementary material, which is available to authorized users.
Highlights
Some patients with chronic kidney disease do not respond adequately to erythropoiesis-stimulating agent (ESA) treatment; these patients are referred to as erythropoiesis-stimulating agents (ESAs) hyporesponders
Longitudinal definitions of ESA hyporesponse The definition of chronic ESA hyporesponsiveness was based on the consideration: after how many months of consecutive hyporesponsiveness is it unlikely that patients will subsequently regain ESA responsiveness? For this study, we considered all patients who met criteria for ESA hyporesponse at baseline and conducted a Kaplan Meier analysis to characterize time to restitution of ESA responsiveness
We performed a similar analysis for the month of July 2011 and observed a similar proportion of patients who met the criteria for ESA hyporesponse (11.56 %) (Additional file 1: Table S1)
Summary
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. It is estimated that at any time approximately 85 % of hemodialysis patients in the United States are treated with erythropoiesis-stimulating agents (ESAs) [1] such as epoetin alfa, which are recombinant human biologic products of the peptide hormone erythropoietin. Erythropoietin and ESAs enhance red blood cell production in the bone marrow, subsequently increasing hemoglobin thereby avoiding transfusion in treated patients. ESA dose is titrated to target a desired hemoglobin concentration [2]. The doses of ESA necessary to achieve a specific hemoglobin concentration can fluctuate with patient circumstances such as the occurrence of infections, illnesses and hospitalizations, and changes in iron stores [3,4,5].
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