A novel assay provides sensitive measurement of physiologically relevant changes in albumin permeability in isolated human and rodent glomeruli.
A novel assay provides sensitive measurement of physiologically relevant changes in albumin permeability in isolated human and rodent glomeruli.
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DOI：
10.1016/j.kint.2017.12.003
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发表时间：
2018-05
影响因子：
19.6
通讯作者：
Foster RR
中科院分区：
文献类型：
--
作者：
Desideri S;Onions KL;Qiu Y;Ramnath RD;Butler MJ;Neal CR;King MLR;Salmon AE;Saleem MA;Welsh GI;Michel CC;Satchell SC;Salmon AHJ;Foster RR
尿白蛋白排泄增加是肾小球疾病的一个关键特征，但作为肾小球通透性的测量有局限性。在这里，我们描述了一种新的测定方法来测量肾小球中单个毛细血管的明显白蛋白通透性，从清除红细胞的灌注肾中分离出来。用共聚焦显微镜定量测定毛细血管腔内白蛋白浓度的下降速率，并计算表观通透性。该分析得到了广泛的验证，并提供了肾小球白蛋白通透性的可靠、可重复的估计。这些值与先前的体内数据相当，表明该方法可以应用于人类和啮齿动物肾小球。为了证实这一点，我们发现靶向内皮糖萼破坏导致小鼠肾小球白蛋白通透性增加。此外，与缓解期血浆相比，移植后肾病综合征复发患者的血浆孵育可增加大鼠肾小球白蛋白通透性。最后，在早期糖尿病大鼠的肾小球中，白蛋白通透性显著增加，内皮糖萼丢失，血管生成素-1可以改善这两种情况。因此，研究人员开发并验证了一种能够产生生理学相关值的肾小球渗透性测定方法，该方法具有足够的灵敏度来测量肾小球渗透性的变化，并且独立于小管功能。该试验显著提高了研究啮齿动物和人类肾小球生物学和疾病的能力。
Increased urinary albumin excretion is a key feature of glomerular disease but has limitations as a measure of glomerular permeability. Here we describe a novel assay to measure the apparent albumin permeability of single capillaries in glomeruli, isolated from perfused kidneys cleared of red blood cells. The rate of decline of the albumin concentration within the capillary lumen was quantified using confocal microscopy and used to calculate apparent permeability. The assay was extensively validated and provided robust, reproducible estimates of glomerular albumin permeability. These values were comparable with previous in vivo data, showing this assay could be applied to human as well as rodent glomeruli. To confirm this, we showed that targeted endothelial glycocalyx disruption resulted in increased glomerular albumin permeability in mice. Furthermore, incubation with plasma from patients with post-transplant recurrence of nephrotic syndrome increased albumin permeability in rat glomeruli compared to remission plasma. Finally, in glomeruli isolated from rats with early diabetes there was a significant increase in albumin permeability and loss of endothelial glycocalyx, both of which were ameliorated by angiopoietin-1. Thus, a glomerular permeability assay, producing physiologically relevant values with sufficient sensitivity to measure changes in glomerular permeability and independent of tubular function, was developed and validated. This assay significantly advances the ability to study biology and disease in rodent and human glomeruli.
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影响因子：
13.6
作者：
Dessapt-Baradez, Cecile;Woolf, Adrian S.;Gnudi, Luigi
通讯作者：
Gnudi, Luigi
影响因子：
--
作者：
HUXLEY, VH;CURRY, FE;ADAMSON, RH
通讯作者：
ADAMSON, RH
DOI：
10.2215/cjn.08160813
发表时间：
2014-04-07
影响因子：
9.8
作者：
Dane, Martijn J. C.;Khairoun, Meriem;Rabelink, Ton J.
通讯作者：
Rabelink, Ton J.
影响因子：
19.6
作者：
BERTOLATUS, JA;HUNSICKER, LG
通讯作者：
HUNSICKER, LG
DOI：
10.1152/ajprenal.00227.2001
发表时间：
2003-10-01
影响因子：
4.2
作者：
Ciarimboli, G;Hjalmarsson, C;Haraldsson, B
通讯作者：
Haraldsson, B