Kågedal Bertil, Mandenius Carl-Fredrik
Department of Clinical Chemistry and Clinical Pharmacology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Division of Biophysics and Bioengineering, IFM, Linköping University, Linköping, Sweden.
Clin Chim Acta. 2024 Jul 15;561:119823. doi: 10.1016/j.cca.2024.119823. Epub 2024 Jun 23.
There are several shortcomings in present methods for estimation of GFR from plasma clearance. The aim of the present study was therefore to develop a physiologically based method for calculation of plasma clearance of iohexol.
A mechanistic model founded on classical biochemical engineering principles where in- and outgoing molecular flows of iohexol between plasma and surrounding tissues were balanced over time. After intravenous injections of iohexol, plasma samples were taken from the investigated subjects until complete elimination of iohexol. After tuning of the model parameters, the clearance value was calculated from the injected dose and the integral of the iohexol concentrations over the investigated period.
The mass balance model was able to predict the time course of iohexol distribution and elimination after parameterization of mass balance and kinetic equations. Four model structures were evaluated, all based on model parameters derived from published data and from internal tests, each complied at varying physiological conditions. Iohexol clearance was assessed through the model and compared with calculations from previously practiced methods. When testing the mass balance model on ten healthy subjects, clearance was estimated accurately.
The physiological and mechanistic character of the mass balance model may suggest that its derived clearance comes closer to actual in vivo conditions than data derived from previously practiced calculation methods. Although here, only verified with the clearance marker iohexol, the mass balance model should be applicable also to other renal clearance markers.
目前通过血浆清除率估算肾小球滤过率（GFR）的方法存在若干缺陷。因此，本研究的目的是开发一种基于生理学的碘海醇血浆清除率计算方法。
基于经典生化工程原理建立一个机理模型，其中碘海醇在血浆和周围组织之间的进出分子流随时间达到平衡。静脉注射碘海醇后，从研究对象采集血浆样本，直至碘海醇完全清除。在对模型参数进行调整后，根据注射剂量和研究期间碘海醇浓度的积分计算清除率值。
在对质量平衡和动力学方程进行参数化后，质量平衡模型能够预测碘海醇分布和清除的时间进程。评估了四种模型结构，均基于从已发表数据和内部测试得出的模型参数，每种结构在不同生理条件下均符合要求。通过该模型评估碘海醇清除率，并与先前方法的计算结果进行比较。在对10名健康受试者测试质量平衡模型时，清除率得到了准确估算。
质量平衡模型的生理学和机理特性可能表明，其得出的清除率比先前计算方法得出的数据更接近实际体内情况。尽管此处仅用清除标记物碘海醇进行了验证，但质量平衡模型也应适用于其他肾清除标记物。
