Nakamura Y, Myers B D
Department of Medicine, Stanford University School of Medicine, California 94305-5114.
Diabetes. 1988 Sep;37(9):1202-11. doi: 10.2337/diab.37.9.1202.
Differential macromolecule clearances were used to elucidate the mechanism of proteinuria in patients with diabetic glomerulopathy. Uncharged dextrans of graded size, combined with albumin and IgG separated into narrow fractions of varying charge by preparative electrofocusing, were used to probe the filtration barrier. Analysis of the fractional clearance profile of dextrans in the 30- to 60-A interval revealed a small fraction of filtrate volume (0.0023-0.0097) permeating large nonrestrictive glomerular pores and correlating strongly with the fractional clearances of albumin (r = .88, P less than .001) or IgG (r = .91, P less than .001). The fractional clearance of the most anionic species of albumin [isoelectric point (pI) 4.0-4.5] significantly exceeded that of less anionic species (pI 4.5-5.5) at all levels of proteinuria. A corresponding increase in fractional clearance of anionic (pI 4.5-5.0) over neutral (pI 7.0-7.5) IgG species was observed in patients with subnephrotic-range proteinuria. We conclude that a loss of barrier size selectivity underlies proteinuria in diabetic glomerulopathy. In addition, either facilitated filtration of polyanions or preferential tubular reabsorption of polycations can be invoked to explain the final composition of urinary protein. Similar loss of size selectivity combined with enhanced fractional clearance of anionic IgG in a group of nondiabetic patients with nephrotic syndrome indicates that the foregoing abnormality of renal protein handling is not unique to diabetic glomerulopathy.
采用不同的大分子清除率来阐明糖尿病肾小球病患者蛋白尿的机制。使用分级大小的不带电荷的葡聚糖，结合通过制备性电聚焦分离成不同电荷窄级分的白蛋白和IgG，来探测滤过屏障。对30至60埃区间内葡聚糖的分数清除率曲线分析显示，一小部分滤液体积（0.0023 - 0.0097）通过大的非限制性肾小球孔渗透，并且与白蛋白（r = 0.88，P < 0.001）或IgG（r = 0.91，P < 0.001）的分数清除率密切相关。在所有蛋白尿水平下，白蛋白最具阴离子性的种类[等电点（pI）4.0 - 4.5]的分数清除率显著超过阴离子性较弱的种类（pI 4.5 - 5.5）。在亚肾病范围蛋白尿患者中观察到，阴离子性（pI 4.5 - 5.0）IgG种类相对于中性（pI 7.0 - 7.5）IgG种类的分数清除率相应增加。我们得出结论，屏障大小选择性的丧失是糖尿病肾小球病蛋白尿的基础。此外，可以用多阴离子的易化滤过或多阳离子的优先肾小管重吸收来解释尿蛋白的最终组成。一组非糖尿病肾病综合征患者中类似的大小选择性丧失以及阴离子性IgG分数清除率的增加表明，上述肾脏蛋白质处理异常并非糖尿病肾小球病所特有。
