Using dynamic treatment regimes to understand erythropoietin-stimulating agent hyporesponsiveness
Erythropoietin-stimulating agent hyporesponsiveness (ESAH) is associated with increased cardiovascular mortality in patients with end-stage renal disease (ESRD) on hemodialysis. Dynamic treatment regimes (DTR), a clinical decision support (CDS) tool that guides the prescription of specific therapies in response to variations in patient states, have been used to guide treatment for chronic illnesses that require frequent monitoring and therapy changes. Our objective is to explore the role of utilizing a DTR to reduce ESAH in pediatric hemodialysis patients.
Retrospective analysis of ESRD patients on hemodialysis who received ESAs. Dosing was adjusted using a locally developed protocol designed to target a hemoglobin between 10 and 12 g/dl. Analyzing this protocol as a DTR, we assessed adherence to the protocol over time measuring how the hyporesponse index (ESA dose/hemoglobin value) changed due to varying levels of adherence.
Eighteen patients met study criteria. Median hemoglobin was 11.4 g/dl (range 6.1–15.4), and median weekly ESA dose (darbepoetin-equivalent) was 0.4 mcg/kg/dose (range 0–2.1). Full adherence to the DTR was identified in 266 (71%) of the 4-week periods, with a median average adherence score of 0.80 (range 0.63–0.91). As adherence to the DTR improved, ESAH decreased. During the last 12 weeks, 13 out of 18 patients had lower average ESA/hemoglobin ratio than the first 12 weeks.
A DTR appears to be well-suited to the treatment of anemia in ESRD and reduces ESAH. Our work shows the potential of DTRs to drive the development and evaluation of clinical practice guidelines.
KeywordsAnemia Hemoglobin Dynamic treatment regime End-stage renal disease (ESRD) Pediatrics Hemodialysis Erythropoietin-stimulating agent hyporesponsiveness (ESAH)
Dr. Pollack participated in the planning, conduct, and analysis of the research, as well as writing all drafts of the manuscript. Dr. Oron developed the analytic approach and then performed a majority of the analysis and helped with writing the manuscript. Dr. Flynn was involved in reviewing the data, and with preparing and reviewing the manuscript. Dr. Munshi came up with the idea for the study, participated in reviewing the data, and contributed to the final manuscript. All authors have contributed significantly to the final manuscript.
Compliance with ethical standards
This study was supported by the Seattle Children’s Center for Clinical and Translational Research Faculty Research Support Fund program. In addition, our work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1 TR002319. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict of interest
The authors declare that they have no conflicts of interest.
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