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人类微小病变性肾病中的肾小球电荷改变

Glomerular charge alterations in human minimal change nephropathy.

作者信息

Bridges C R, Myers B D, Brenner B M, Deen W M

出版信息

Kidney Int. 1982 Dec;22(6):677-84. doi: 10.1038/ki.1982.229.

DOI:10.1038/ki.1982.229
PMID:6186837
Abstract

A theoretical model of charge and size selectivity for the glomerulus has been applied to human data. Using previously published values for GFR, renal plasma flow, systemic oncotic pressure, and fractional clearances of neutral dextrans, albumin, salivary amylase, and transferrin, membrane parameters describing the glomerular barrier were determined for normal individuals under control conditions and during lysine infusion (which retards tubule protein reabsorption), and for patients with minimal change nephropathy (MCN). To permit the estimation of membrane charge from fractional clearances, molecular charge values for human transferrin (-9.4 Eq/mole) and human salivary amylase (-4.1) were determined by measuring electrophoretic mobilities of these proteins in polyacrylamide gels. Assuming no large changes in the transmural hydraulic pressure difference (delta P), the glomerular ultrafiltration coefficient (Kf, the product of hydraulic permeability and capillary surface area) was calculated to be reduced by greater than 50% in MCN. The effective pore radius (approximately 55 A) is virtually unaltered in MCN, suggesting that the decline in Kf is due to a reduced number of pores. The degree of albuminuria observed in MCN is attributable to an approximately 50% reduction in the concentration of fixed negative charges in the glomerular capillary wall. The concentrations of fixed charges calculated from albumin data in normal individuals (140 to 160 mEq/liter) and in patients with MCN (60 to 90 mEq/liter) are insensitive to the assumed values of delta P.

摘要

肾小球电荷和大小选择性的理论模型已应用于人体数据。利用先前发表的肾小球滤过率(GFR)、肾血浆流量、全身胶体渗透压以及中性右旋糖酐、白蛋白、唾液淀粉酶和转铁蛋白的分数清除率值,确定了正常个体在对照条件下和赖氨酸输注期间(这会延迟肾小管蛋白重吸收)以及微小病变肾病(MCN)患者的描述肾小球屏障的膜参数。为了从分数清除率估计膜电荷,通过测量这些蛋白质在聚丙烯酰胺凝胶中的电泳迁移率,确定了人转铁蛋白(-9.4 Eq/摩尔)和人唾液淀粉酶(-4.1)的分子电荷值。假设跨膜液压差(ΔP)无大的变化,计算得出MCN患者的肾小球超滤系数(Kf,水力渗透率与毛细血管表面积的乘积)降低超过50%。MCN患者的有效孔径半径(约55 Å)实际上未改变,这表明Kf的下降是由于孔数量减少。MCN患者中观察到的蛋白尿程度可归因于肾小球毛细血管壁中固定负电荷浓度降低约50%。根据正常个体(140至160 mEq/升)和MCN患者(60至90 mEq/升)的白蛋白数据计算出的固定电荷浓度对假设的ΔP值不敏感。

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Glomerular charge alterations in human minimal change nephropathy.人类微小病变性肾病中的肾小球电荷改变
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