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糖尿病肾病中蛋白尿的机制:肾小球屏障功能研究

Mechanisms of proteinuria in diabetic nephropathy: a study of glomerular barrier function.

作者信息

Myers B D, Winetz J A, Chui F, Michaels A S

出版信息

Kidney Int. 1982 Apr;21(4):633-41. doi: 10.1038/ki.1982.71.

DOI:10.1038/ki.1982.71
PMID:6178872
Abstract

The fractional clearance of neutral dextrans (theta D) with Einstein-Stokes radii between 30 and 64 A was determined in normal subjects (controls, N = 15) and in diabetic patients with heavy proteinuria (advanced nephropathy, N = 16) or trace proteinuria (early nephropathy, N = 8). When plotted on log normal probability coordinates, the correlation between theta D and radius in controls and in early diabetic nephropathy was linear, suggesting that glomerular pores form one population with a normal distribution. In advanced diabetic nephropathy, however, theta D for large molecules (radius greater than 46 A) was elevated and departed from linearity suggesting a bimodal pore size distribution within the glomerular membrane. A mathematical model was devised, which revealed the mean fraction of glomerular filtrate permeating the upper pore mode to be 0.009 +/- 0.002, and the pores to be totally nondiscriminatory toward molecules with radii up to 64 A. We conclude that the development of large pores (or defects) within the glomerular membrane in advanced diabetic nephropathy permits the unrestricted passage of large plasma proteins into the urine.

摘要

在正常受试者(对照组,N = 15)以及患有重度蛋白尿的糖尿病患者(晚期肾病,N = 16)或微量蛋白尿的糖尿病患者(早期肾病,N = 8)中,测定了爱因斯坦-斯托克斯半径在30至64埃之间的中性右旋糖酐的分数清除率(θD)。当绘制在对数正态概率坐标上时,对照组和早期糖尿病肾病患者中θD与半径之间的相关性呈线性,这表明肾小球孔形成了一个呈正态分布的群体。然而,在晚期糖尿病肾病中,大分子(半径大于46埃)的θD升高且偏离线性,这表明肾小球膜内存在双峰孔径分布。设计了一个数学模型,该模型显示透过上孔径模式的肾小球滤过液的平均分数为0.009±0.002,并且这些孔对半径达64埃的分子完全没有选择性。我们得出结论,晚期糖尿病肾病中肾小球膜内大孔(或缺陷)的形成使得大量血浆蛋白能够不受限制地进入尿液。

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