Lazzara Matthew J, Deen William M
Dept. of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA.
Am J Physiol Renal Physiol. 2007 Jan;292(1):F430-9. doi: 10.1152/ajprenal.00010.2006. Epub 2006 Sep 5.
Normally, the small amount of albumin which passes through the glomerular capillary wall is almost completely reabsorbed in the proximal tubule, via an endocytic mechanism, but the reabsorptive process can be overwhelmed if the filtered load of albumin is too large. To examine the factors that control the fractional reabsorption of albumin (f), we developed a mathematical model which assumes saturable endocytosis kinetics with a maximum reabsorptive capacity, V(max), and which includes the effects of flow and diffusion in the lumen. Limitations in albumin transport from the bulk tubule fluid to the endocytic sites at the bases of the microvilli had only a modest (8%) effect on the value of V(max) needed to fit micropuncture data on tubule albumin concentrations in rats. For moderate changes in filtered load, there was much greater sensitivity of f to SNGFR than to the albumin concentration of the filtrate (C(0)). A 50% increase in SNGFR was predicted to cause four- to fivefold increases in albumin excretion in rats or humans. For large increases in C(0), as might result from defects in glomerular sieving, there was a threshold at which the reabsorptive process became saturated and f fell sharply. That threshold corresponded to sieving coefficients of 10(-3) to 10(-2), the higher values occurring at reduced SNGFR. The predictions of the present model contrast with those of one proposed recently by Smithies (32), which does not include the effects of tubule flow rate.
正常情况下，通过肾小球毛细血管壁的少量白蛋白几乎完全在近端小管中通过内吞机制被重吸收，但如果白蛋白的滤过量过大，重吸收过程可能会不堪重负。为了研究控制白蛋白分数重吸收（f）的因素，我们建立了一个数学模型，该模型假设内吞动力学具有饱和性，最大重吸收能力为V(max)，并包括管腔内流动和扩散的影响。白蛋白从肾小管管腔液向微绒毛基部内吞位点的转运限制对拟合大鼠肾小管白蛋白浓度微穿刺数据所需的V(max)值仅有适度（8%）的影响。对于滤过量的适度变化，f对单个肾单位肾小球滤过率（SNGFR）的敏感性远高于对滤液中白蛋白浓度（C(0)）的敏感性。预计SNGFR增加50%会导致大鼠或人类白蛋白排泄增加4至5倍。对于C(0)的大幅增加，如可能由肾小球滤过缺陷导致的情况，存在一个阈值，超过该阈值重吸收过程会饱和，f会急剧下降。该阈值对应于筛分系数为10(-3)至10(-2)，SNGFR降低时会出现较高的值。本模型的预测结果与Smithies（32）最近提出的模型不同，后者未考虑肾小管流速的影响。
