Department of Pharmaceutical Sciences, The State University of New York at Buffalo, 370 Pharmacy Building, Buffalo, New York, 14214, USA.
Department of Pharmacy Practice, The State University of New York at Buffalo, Buffalo, New York, USA.
AAPS J. 2020 Feb 3;22(2):40. doi: 10.1208/s12248-020-0424-9.
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.
红细胞(RBC)寿命缩短是终末期肾病(ESRD)患者贫血的主要因素之一,应在贫血管理方案中考虑。在这项研究中,我们旨在估计 ESRD 患者的 RBC 寿命和个体间变异性的来源。使用个体参数(经验贝叶斯估计)来预测 2 周后的血红蛋白浓度。使用基于网织红细胞的 RBC 寿命估计(REBEL)和 RBC 计数数据的群体建模。本分析共纳入 24 例接受皮下重组人促红细胞生成素(rHuEPO)维持剂量治疗的患者,在 10 周内每两周采集 120 份血样。典型的 RBC 寿命估计为 63.3 天。发现 RBC 寿命随铁代谢中最近发现的激素之一红细胞生成素(erythroferrone)而增加。血浆红细胞生成素增加约 10%,RBC 寿命增加约 5%。此外,女性的 RBC 寿命比男性短 18.7%。在 24 名受试者中,有 16 名的血红蛋白浓度在 95%预测区间内。中位绝对预测误差为 15.9%(四分位距,9.5 至 24.7%)。我们证明,REBEL 与群体建模技术相结合可有效用于估计 RBC 寿命。然后,个体参数可用于预测 ESRD 患者未来的血红蛋白浓度。