Drumond M C, Kristal B, Myers B D, Deen W M
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.
J Clin Invest. 1994 Sep;94(3):1187-95. doi: 10.1172/JCI117435.
Previous studies have established that in a variety of human glomerulopathies the reduced glomerular filtration rate (GFR) is due to a marked lowering of the ultrafiltration coefficient (Kf). To identify the factors which lower Kf, we measured the filtering surface area per glomerulus, filtration slit frequency, basement membrane thickness, and GFR and its determinants in patients with minimal change and membraneous nephropathies and in age-matched healthy controls. Overall values of Kf for the two kidneys were calculated from GFR, renal plasma flow rate, systemic colloid osmotic pressure, and three assumed values for the transcapillary pressure difference. "Experimental" values of the glomerular hydraulic permeability (kexp) were then calculated from Kf, glomerular filtering surface area, and estimates of the total number of nephrons of the two kidneys. Independent estimates of the glomerular hydraulic permeability (kmodel) were obtained using a recent mathematical model that is based on analyses of viscous flow through the various structural components of the glomerular capillary wall. Individual values of basement membrane thickness and filtration slit frequency were used as inputs in this model. The results indicate that the reductions of Kf in both nephropathies can be attributed entirely to reduced glomerular hydraulic permeability. The mean values of kexp and kmodel were very similar in both disorders and much smaller in the nephrotic groups than in healthy controls. There was good agreement between kexp and kmodel for any given group of subjects. It was shown that, in both groups of nephrotics, filtration slit frequency was a more important determinant of the water flow resistance than was basement membrane thickness. The decrease in filtration slit frequency observed in both disorders caused the average path length for the filtrate to increase, thereby explaining the decreased hydraulic permeability.
以往的研究已证实，在多种人类肾小球疾病中，肾小球滤过率（GFR）降低是由于超滤系数（Kf）显著下降所致。为了确定降低Kf的因素，我们测量了微小病变和膜性肾病患者以及年龄匹配的健康对照者单个肾小球的滤过表面积、滤过裂隙频率、基底膜厚度、GFR及其决定因素。根据GFR、肾血浆流量、全身胶体渗透压以及跨毛细血管压力差的三个假定值计算出双肾Kf的总体值。然后根据Kf、肾小球滤过表面积以及对双肾肾单位总数的估计值计算出肾小球水力传导率（kexp）的“实验”值。使用基于对通过肾小球毛细血管壁各结构成分的粘性流分析的最新数学模型，获得了肾小球水力传导率（kmodel）的独立估计值。该模型将基底膜厚度和滤过裂隙频率的个体值用作输入。结果表明，两种肾病中Kf的降低完全可归因于肾小球水力传导率降低。两种疾病中kexp和kmodel的平均值非常相似，肾病组的值比健康对照组小得多。对于任何给定的受试者组，kexp和kmodel之间都有很好的一致性。结果表明，在两组肾病患者中，滤过裂隙频率比基底膜厚度是水流阻力更重要的决定因素。在两种疾病中观察到的滤过裂隙频率降低导致滤液的平均路径长度增加，从而解释了水力传导率降低的原因。
