Burne M J, Osicka T M, Comper W D
Department of Biochemistry and Molecular Biology, Monash University, Clayton, and the Endocrine Unit, Austin and Repatriation Medical Center, Heidelberg, Victoria, Australia.
Kidney Int. 1999 Jan;55(1):261-70. doi: 10.1046/j.1523-1755.1999.00234.x.
The purported existence of "large pores" in the glomerular capillary wall has been derived primarily from studies using dextrans and Ficolls. Systematic studies using high molecular weight proteins have not been performed. One of the difficulties is that recent studies have demonstrated that albumin and other proteins undergo degradation during renal passage. Our study took into account this renal degradation in measuring the fractional clearance of various high molecular weight proteins (the hydrodynamic radii range was between 48 to 70 A).
Fractional clearances of tritium-labeled proteins were measured using ALZET osmotic pumps, which are designed to release a slow continuous infusion of tracer. Blood and urine collections were taken at 24-hour intervals over seven days and were counted for radioactivity, and glomerular filtration rate was measured by a creatinine assay.
Steady-state levels of [3H]protein in plasma were obtained by day 6. The [3H]proteins in the plasma showed no degradation. The fractional clearances (mean +/- sd, N = 5) of the various proteins were albumin (radius = 36 A; 0.0023 +/- 0.0009), transferrin (48 A; 0.0046 +/- 0.0007), lactoperoxidase (58 A; 0. 0045 +/- 0.0005), immunoglobulin G (62 A; 0.0043 +/- 0.0009), lactate dehydrogenase (64 A; 0.0041 +/- 0.0009), and glucose oxidase (70 A; 0.0036 +/- 0.0011).
These values suggest a weak dependence of fractional clearance on size-selective filtration, except for albumin, which undergoes a specific type of postglomerular processing. The fractional clearances were higher than expected from previous data on dextrans and Ficolls of equivalent hydrodynamic radius, and thus demonstrate that "large pores" may already exist in normal glomerular capillary walls.
肾小球毛细血管壁中“大孔”的所谓存在主要源于使用葡聚糖和聚蔗糖的研究。尚未进行使用高分子量蛋白质的系统研究。困难之一在于最近的研究表明白蛋白和其他蛋白质在肾脏通过过程中会发生降解。我们的研究在测量各种高分子量蛋白质（流体动力学半径范围在48至70埃之间）的分数清除率时考虑了这种肾脏降解。
使用ALZET渗透泵测量氚标记蛋白质的分数清除率，该渗透泵设计用于缓慢持续输注示踪剂。在七天内每隔24小时采集血液和尿液样本并计数放射性，通过肌酐测定法测量肾小球滤过率。
到第6天时血浆中[3H]蛋白质达到稳态水平。血浆中的[3H]蛋白质未显示降解。各种蛋白质的分数清除率（平均值±标准差，N = 5）分别为白蛋白（半径 = 36埃；0.0023±0.0009）、转铁蛋白（48埃；0.0046±0.0007）、乳过氧化物酶（58埃；0.0045±0.0005）、免疫球蛋白G（62埃；0.0043±0.0009）、乳酸脱氢酶（64埃；0.0041±0.0009）和葡萄糖氧化酶（70埃；0.0036±0.0011）。
这些值表明分数清除率对尺寸选择性滤过的依赖性较弱，但白蛋白除外，白蛋白会经历特定类型的肾小球后处理。分数清除率高于先前关于等效流体动力学半径的葡聚糖和聚蔗糖的数据预期，因此表明正常肾小球毛细血管壁中可能已经存在“大孔”。
