Nature of the glomerular capillary injury in human membranous glomerulopathy.
Nature of the glomerular capillary injury in human membranous glomerulopathy.
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人膜性肾小球病肾小球毛细血管损伤的性质。
DOI：
10.1172/jci112384
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Myers,BD
中科院分区：
文献类型：
--
作者：
Shemesh,O;Ross,JC;Deen,WM;Grant,GW;Myers,BD
本文应用微分溶质清除技术对20例膜性肾小球病伴大量蛋白尿患者的肾小球毛细血管壁功能进行了评价。在20名健康志愿者中，菊粉的清除率、滤过分数和半径为28-48 A的不带电葡聚糖的清除分数显著低于对照值（P <0.01）。相反，半径大于50的右旋糖酐的清除率明显升高。描述肾小球毛细血管壁的主要部分为等孔膜和次要部分为非歧视性分流途径的溶质转运的理论模型显示，计算的肾小球超滤系数低5倍，主要膜组分的平均孔半径比对照值小4 A。然而，渗透分流通路的滤液体积分数是对照值的3 - 4倍，并且在个体患者中与白蛋白（r = 0.76）和IgG（r = 0.80）的清除率分数密切相关。在吲哚美辛治疗期间，7例患者的肾血浆流量降低24%，导致蛋白尿减少74%，同时通过分流途径形成的滤液相应减少。肾小球超微结构的形态计量学分析显示，肾小球滤过率和尿蛋白渗漏的抑郁症的程度密切相关的肾小球毛细血管壁的上皮层的变化，但不上皮下免疫沉积物的密度。我们的结论是，膜性肾小球病的肾小球毛细血管的特征是超滤能力和屏障大小选择性的丧失，上皮下免疫沉积并不能为这些功能改变提供结构基础。图片
A differential solute clearance technique was used to evaluate glomerular capillary wall function in 20 patients with membranous glomerulopathy and massive proteinuria. The clearance of inulin, the filtration fraction, and the fractional clearance of uncharged dextrans of a radius of 28-48 A were depressed significantly below control values in 20 healthy volunteers (P less than 0.01). In contrast, the fractional clearance of dextrans of radius greater than 50 A was elevated markedly. A theoretical model of solute transport that depicts the major portion of the glomerular capillary wall as an isoporous membrane and the minor portion as a nondiscriminatory shunt pathway revealed the calculated glomerular ultrafiltration coefficient to be five times lower and mean pore radius of the major membrane component to be 4 A smaller than control values. However, the fraction of filtrate volume permeating the shunt pathway was three- to fourfold above control values and correlated strongly in individual patients with the fractional clearance of albumin (r = 0.76) and of IgG (r = 0.80). Lowering renal plasma flow by 24% during indomethacin therapy in seven patients resulted in a 74% reduction in proteinuria accompanied by a corresponding diminution of filtrate formed through the shunt pathway. Morphometric analysis of glomerular ultrastructure revealed the magnitude of depression of the glomerular filtration rate and of urinary protein leakage to be related strongly to changes in the epithelial layer of the glomerular capillary wall, but not to the density of subepithelial immune deposits. We conclude that glomerular capillaries in membranous glomerulopathy are characterized by a loss of ultrafiltration capacity and of barrier size-selectivity, and that subepithelial immune deposits do not provide a structural basis for these functional alterations.Images