Department of Biomedicine, Aarhus University, Aarhus, Denmark.
J Am Soc Nephrol. 2012 Apr;23(4):591-6. doi: 10.1681/ASN.2011101034. Epub 2012 Jan 26.
Urinary albumin excretion is an important diagnostic and prognostic marker of renal function. Both animal and human urine contain large amounts of albumin fragments, but whether these fragments originate from renal tubular degradation of filtered albumin is unknown. Here, we used mice with kidneys lacking megalin and cubilin, the coreceptors that mediate proximal tubular endocytosis of albumin, to determine whether proximal tubular degradation of albumin forms the detectable urinary albumin fragments. After intravenous administration of (125)I-labeled mouse albumin to knockout and control mice, we examined kidney uptake of albumin and urinary excretion of both intact albumin and its fragments using size exclusion chromatography. In control mice, all labeled albumin eluted as albumin fragments in the urine. In megalin/cubilin-deficient mice, we observed decreased uptake and degradation of albumin and increased urinary excretion of intact albumin; we did not, however, detect a decrease in the excretion of albumin fragments. These results show that the generation of urinary albumin fragments occurs independently of renal tubular uptake and degradation of albumin, suggesting that the pathophysiological implications of changes in urinary albumin fragments require reevaluation.
尿白蛋白排泄是肾功能的一个重要诊断和预后标志物。动物和人尿中都含有大量的白蛋白片段，但这些片段是否来源于滤过白蛋白的肾小管降解尚不清楚。在这里，我们使用缺乏介导白蛋白近端肾小管内吞作用的核心受体巨球蛋白和 cubilin 的小鼠来确定白蛋白的近端肾小管降解是否形成可检测的尿白蛋白片段。在给敲除和对照小鼠静脉注射（125）I 标记的鼠白蛋白后，我们使用排阻色谱法检查了肾脏对白蛋白的摄取和完整白蛋白及其片段的尿排泄。在对照小鼠中，所有标记的白蛋白在尿液中均以白蛋白片段的形式洗脱。在巨球蛋白/cubilin 缺陷小鼠中，我们观察到白蛋白的摄取和降解减少，完整白蛋白的尿排泄增加；然而，我们没有检测到白蛋白片段的排泄减少。这些结果表明，尿白蛋白片段的产生独立于肾小管对白蛋白的摄取和降解，这表明尿白蛋白片段变化的病理生理意义需要重新评估。
