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红细胞生存数据建模。

Modeling red blood cell survival data.

机构信息

School of Pharmacy, University of Otago, Dunedin, New Zealand.

出版信息

J Pharmacokinet Pharmacodyn. 2011 Dec;38(6):787-801. doi: 10.1007/s10928-011-9220-6. Epub 2011 Oct 14.

Abstract

Anaemia of chronic kidney disease (CKD) is a common complication in patients with renal impairment, especially in end-stage renal failure. As well as erythropoietin deficiency, decreased red blood cell survival is a contributing factor. However, it remains unclear which mechanism underlies the altered survival of red blood cells (RBCs). In this work a previously developed statistical model for RBC survival was applied to clinical data obtained from 14 patients with CKD undergoing hemodialysis as well as 14 healthy controls using radioactive chromium (⁵¹Cr) as random labelling method. A classical two-stage approach and a full population analysis were applied to estimate the key parameters controlling random destruction and senescence in the model. Estimating random destruction was preferred over estimating an accelerated senescence in both approaches and both groups as it provided the better fit to the data. Due to significant nonspecific random loss of the label from the cells that cannot be quantified directly only a relative RBC survival can be obtained from data using ⁵¹Cr as labelling method. Nevertheless, RBC survival was found to be significantly reduced in CKD patients compared to the controls with a relative reduction of 20-30% depending on the analysis method used.

摘要

慢性肾脏病(CKD)贫血是肾功能损害患者,尤其是终末期肾衰竭患者的常见并发症。除了促红细胞生成素缺乏外,红细胞(RBC)生存能力下降也是一个促成因素。然而,改变 RBC 生存能力的机制仍不清楚。在这项工作中,我们应用先前开发的 RBC 生存统计模型,对 14 名接受血液透析的 CKD 患者和 14 名健康对照者的临床数据进行了分析,使用放射性铬(⁵¹Cr)作为随机标记方法。应用经典的两阶段方法和全人群分析来估计模型中控制随机破坏和衰老的关键参数。在两种方法和两组中,估计随机破坏优于估计加速衰老,因为它更符合数据。由于无法直接定量标记从细胞中不可避免的非特异性随机丢失,因此仅使用 ⁵¹Cr 作为标记方法从数据中获得相对 RBC 生存能力。然而,与对照组相比,CKD 患者的 RBC 生存能力显著降低,具体降低程度取决于所使用的分析方法,为 20-30%。

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