Morelli E, Loon N, Meyer T, Peters W, Myers B D
Department of Medicine, Stanford University School of Medicine, California.
Diabetes. 1990 Jan;39(1):76-82. doi: 10.2337/diacare.39.1.76.
Differential solute clearances were used to examine the effects of a 90-day course of enalapril on glomerular barrier function in 16 proteinuric patients with diabetic glomerulopathy. By day 90, plasma renin and prorenin became elevated, and arterial pressure declined. Transglomerular passage of dextrans of broad size distribution (radii 28-60 A) was lowered significantly. In a subset of 8 patients, withdrawal of enalapril was followed after an additional 30 days by a return of renin levels and arterial pressure to pretreatment levels. The dextran-sieving profile also returned to baseline, becoming uniformly elevated above treated day-90 levels. A theoretical analysis of the serial dextran-sieving profiles indicated that enalapril shifted glomerular pore size distribution to smaller size. These changes in barrier size selectivity were associated with a reduction in fractional albumin and IgG clearances during enalapril therapy and a subsequent rise in these quantities after its withdrawal; urinary protein excretion rate tended to vary in parallel. We conclude that inhibition of converting enzyme in humans with established diabetic glomerulopathy diminishes glomerular permeability to proteins by enhancing barrier size selectivity. Because neither enalapril therapy nor its withdrawal influenced the glomerular filtration or renal plasma flow rates significantly, we propose that the primary action of enalapril may be to modulate the intrinsic membrane properties of the glomerular barrier.
采用不同溶质清除率来研究依那普利90天疗程对16例糖尿病性肾小球病蛋白尿患者肾小球屏障功能的影响。到第90天时，血浆肾素和前肾素升高，动脉压下降。宽大小分布（半径28 - 60 Å）的右旋糖酐经肾小球的通透率显著降低。在8例患者的亚组中，停用依那普利30天后，肾素水平和动脉压恢复到治疗前水平。右旋糖酐筛分曲线也恢复到基线，高于治疗第90天时的水平且呈均匀升高。对系列右旋糖酐筛分曲线的理论分析表明，依那普利使肾小球孔径分布向更小尺寸转变。屏障大小选择性的这些变化与依那普利治疗期间白蛋白和IgG清除率分数降低以及停药后这些量随后升高有关；尿蛋白排泄率往往与之平行变化。我们得出结论，在已患糖尿病性肾小球病的患者中，抑制转化酶可通过增强屏障大小选择性来降低肾小球对蛋白质的通透性。由于依那普利治疗及其停药均未显著影响肾小球滤过率或肾血浆流量，我们认为依那普利的主要作用可能是调节肾小球屏障的固有膜特性。
