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Application of Reticulocyte-Based Estimation of Red Blood Cell Lifespan in Anemia Management of End-Stage Renal Disease Patients

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Abstract

Shortened red blood cell (RBC) lifespan is one of the major factors contributing to anemia in end-stage renal disease (ESRD) patients and should be taken into account in anemia management protocols. In this study, we aimed to estimate RBC lifespan and the source of between-subject variability in ESRD patients. The resulting individual parameters (empirical Bayes estimates) were used to predict hemoglobin concentrations 2 weeks in advance. The reticulocyte-based estimation of RBC lifespan (REBEL) and the population modeling of RBC count data were used. A total of 120 blood samples collected biweekly over 10 weeks in 24 patients receiving maintenance doses of recombinant human erythropoietin (rHuEPO) subcutaneously were included in this analysis. Typical RBC lifespan was estimated to be 63.3 days. RBC lifespan was found to increase with erythroferrone, a recently identified hormone participating in iron metabolism. Approximately, a 10% increase in plasma erythroferrone was associated with a 5% increase in RBC lifespan. In addition, RBC lifespan was 18.7% shorter in females compared with males. Out of 24 subjects, 16 had hemoglobin concentrations predicted within 95% prediction intervals. The median absolute prediction error was 15.9% (interquartile range, 9.5 to 24.7%). We demonstrated that REBEL coupled with the population modeling technique can be used effectively to estimate RBC lifespan. Then, individual parameters can be used to predict future hemoglobin concentrations in ESRD patients.

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Funding

This study was financially supported by the Bristol-Myers Squibb fellowship to Ly Minh Nguyen and the New Investigator Award grant from the American Association of Colleges of Pharmacy to Calvin J. Meaney. The study was performed independently of all funders.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, The State University of New York at Buffalo, 370 Pharmacy Building, Buffalo, New York, 14214, USA

    Ly Minh Nguyen & Wojciech Krzyzanski

  2. Department of Pharmacy Practice, The State University of New York at Buffalo, Buffalo, New York, USA

    Calvin J. Meaney

  3. Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, North Carolina, USA

    Gauri G. Rao

  4. Erie County Medical Center, Regional Center of Excellence for Transplantation and Kidney Care, Buffalo, New York, USA

    Mandip Panesar

Authors
  1. Ly Minh Nguyen
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  2. Calvin J. Meaney
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  3. Gauri G. Rao
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  4. Mandip Panesar
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  5. Wojciech Krzyzanski
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Corresponding author

Correspondence to Wojciech Krzyzanski.

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All procedures performed in this study were approved by the State University of New York at Buffalo Institutional Review Board (STUDY00000261) and in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Nguyen, L.M., Meaney, C.J., Rao, G.G. et al. Application of Reticulocyte-Based Estimation of Red Blood Cell Lifespan in Anemia Management of End-Stage Renal Disease Patients. AAPS J 22, 40 (2020). https://doi.org/10.1208/s12248-020-0424-9

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  • DOI: https://doi.org/10.1208/s12248-020-0424-9

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