CHARGE SELECTIVITY OF THE GLOMERULAR-FILTRATION BARRIER IN HEALTHY AND NEPHROTIC HUMANS
CHARGE SELECTIVITY OF THE GLOMERULAR-FILTRATION BARRIER IN HEALTHY AND NEPHROTIC HUMANS
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DOI：
10.1172/jci116831
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发表时间：
1993-11-01
影响因子：
15.9
通讯作者：
MYERS, BD
中科院分区：
文献类型：
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作者：
GUASCH, A;DEEN, WM;MYERS, BD
我们使用硫酸葡聚糖（DS），以评估屏障电荷选择性在11名非蛋白尿受试者和11例肾病综合征由于膜性肾病或微小病变肾病。H-3-DS制剂跨越10- 24埃的分子半径区间，并在体外显示出大小依赖性蛋白结合。采用凝胶渗透色谱法将尿液和血浆超滤物按大小分离成窄级分。非蛋白尿患者15埃半径的超滤DS的筛分系数（θ）平均为0.68+/-0.03，肾病患者为0.95+/-0.05（P < 0.001）。广泛尺寸分布的不带电葡聚糖用于评价非蛋白尿受试者（n = 19）和具有微小变化（n = 20）或膜性肾病（n = 27）的肾病患者的独立组中的屏障尺寸选择性。在非蛋白尿受试者中，半径相似的不带电右旋糖酐（约18埃）的θ值明显大于DS，但在肾病患者中相似。此外，通过不带电葡聚糖（18- 60埃半径）的筛分特征评估的屏障尺寸选择性受损，未能完全解释几乎一半的轻微变化（9/20）或膜性肾病（12/27）患者中观察到的白蛋白尿水平。这些发现共同表明，人类肾小球毛细血管壁通常为白蛋白等带负电荷的大分子的过滤提供静电屏障，并且这种静电屏障的损害导致肾病综合征中白蛋白尿的严重程度。
We used dextran sulfate (DS) to evaluate barrier charge selectivity in 11 nonproteinuric subjects and in 11 patients with the nephrotic syndrome due to either membranous nephropathy or minimal change nephropathy. The H-3-DS preparation spanned a molecular radius interval of 10-24angstrom and exhibited size-dependent protein binding in vitro. Urine and ultrafiltrates of plasma were separated by size into narrow fractions using gel permeation chromatography. The sieving coefficient (theta) for ultrafilterable DS of 15angstrom radius averaged 0.68+/-0.03 in nonproteinuric vs. 0.95+/-0.05 in nephrotic subjects (P < 0.001). Uncharged dextrans of broad size distribution were used to evaluate barrier size-selectivity in separate groups of nonproteinuric subjects (n = 19) and nephrotic patients with either minimal change (n = 20) or membranous nephropathy (n = 27). The value of theta for an uncharged dextran of similarly small radius (approximately 18angstrom) was significantly larger than that observed for DS in nonproteinuric subjects, but was similar in nephrotic individuals. Further, impaired barrier size-selectivity, as assessed by the sieving profile for uncharged dextrans (18-60angstrom radius), failed to account fully for the observed level of albuminuria in almost half of the patients with either minimal change (9/20) or membranous nephropathy (12/27). Together these findings suggest that the human glomerular capillary wall normally provides an electrostatic barrier to filtration of negatively charged macromolecules such as albumin, and that impairment of this electrostatic barrier contributes to the magnitude of albuminuria in the nephrotic syndrome.