Computational Medicine Group, Global Medical Office, Fresenius Medical Care Germany, Bad Homburg, Germany.
Renal Research Institute, New York, New York, United States of America.
PLoS Comput Biol. 2023 Jan 24;19(1):e1010850. doi: 10.1371/journal.pcbi.1010850. eCollection 2023 Jan.
Patients with renal anemia are frequently treated with erythropoiesis-stimulating agents (ESAs), which are dynamically dosed in order to stabilize blood hemoglobin levels within a specified target range. During typical ESA treatments, a fraction of patients experience hemoglobin 'cycling' periods during which hemoglobin levels periodically over- and undershoot the target range. Here we report a specific mechanism of hemoglobin cycling, whereby cycles emerge from the patient's delayed physiological response to ESAs and concurrent ESA dose adjustments. We introduce a minimal theoretical model that can explain dynamic hallmarks of observed hemoglobin cycling events in clinical time series and elucidates how physiological factors (such as red blood cell lifespan and ESA responsiveness) and treatment-related factors (such as dosing schemes) affect cycling. These results show that in general, hemoglobin cycling cannot be attributed to patient physiology or ESA treatment alone but emerges through an interplay of both, with consequences for the design of ESA treatment strategies.
患有肾性贫血的患者常需要接受促红细胞生成素刺激剂（ESA）治疗，该治疗需要根据情况调整ESA 的剂量，以将患者的血色素水平稳定在特定的目标范围内。在典型的 ESA 治疗中，有一部分患者会经历血色素“波动”期，在此期间，血色素水平会周期性地高于或低于目标范围。在这里，我们报告了一种血红蛋白波动的特定机制，即波动是由患者对 ESA 的延迟生理反应和同时进行的 ESA 剂量调整引起的。我们引入了一个最小理论模型，可以解释临床时间序列中观察到的血红蛋白波动事件的动态特征，并阐明生理因素（如红细胞寿命和 ESA 反应性）和治疗相关因素（如给药方案）如何影响波动。这些结果表明，一般来说，血红蛋白波动不能仅仅归因于患者的生理或 ESA 治疗，而是通过两者的相互作用而出现，这对 ESA 治疗策略的设计有影响。
