Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy.
Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy.
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DOI：
10.1038/ki.2012.234
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发表时间：
2012-11
影响因子：
19.6
通讯作者：
中科院分区：
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2型糖尿病患者的足细胞脱离和内皮细胞窗孔减少以及这些特征与糖尿病肾病经典结构变化之间的关系尚未得到描述。在这里，我们研究了37名患有2型糖尿病的皮马印第安人的这些关系，其中11人有正常白蛋白尿，16人有微量白蛋白尿，10人有大量白蛋白尿。10名肾脏捐赠者（非美国印第安人）的活检显示几乎检测不到（0.03%）足细胞脱离和43.5%内皮细胞开窗。在2型糖尿病患者中，通过比较，足细胞脱离的平均百分比在大量白蛋白尿（1.48%）中显著高于正常白蛋白尿（0.41%）或微量白蛋白尿（0.37%）。足细胞脱离与肾小球足细胞数和蛋白尿显著相关。大量白蛋白尿组内皮细胞开窗率（19.3%）显著低于正常组（27.4%）或微量白蛋白尿组（27.2%），且与肾小球基底膜厚度、白蛋白尿、系膜面积分数和肾小球滤过率（碘酞酸清除率）显著相关。足细胞脱离和内皮细胞窗孔减少不相关，但与糖尿病肾病的典型病变有关。因此，我们的研究结果证实了这些损伤在2型糖尿病肾脏疾病的发展和进展中发挥的重要作用，就像它们在1型糖尿病中一样。足细胞的分离是否为蛋白质逃离肾小球循环创造了通道，以及内皮细胞开窗减少是否降低了肾小球的水力渗透性，还需要进一步的研究。
Podocyte detachment and reduced endothelial cell fenestration and relationships between these features and the classic structural changes of diabetic nephropathy have not been described in patients with type 2 diabetes. Here we studied these relationships in 37 Pima Indians with type 2 diabetes of whom 11 had normal albuminuria, 16 had microalbuminuria, and 10 had macroalbuminuria. Biopsies from ten kidney donors (not Americans Indians) showed almost undetectable (0.03%) podocyte detachment and 43.5% endothelial cell fenestration. In patients with type 2 diabetes, by comparison, the mean percentage of podocyte detachment was significantly higher in macroalbuminuria (1.48%) than in normal albuminuria (0.41%) or microalbuminuria (0.37%). Podocyte detachment correlated significantly with podocyte number per glomerulus and albuminuria. The mean percentage of endothelial cell fenestration was significantly lower in macroalbuminuria (19.3%) than in normal (27.4%) or microalbuminuria (27.2%) and correlated significantly with glomerular basement membrane thickness, albuminuria, fractional mesangial area, and the glomerular filtration rate (iothalamate clearance). Podocyte detachment and diminished endothelial cell fenestration were not correlated, but were related to classic lesions of diabetic nephropathy. Thus, our findings confirm the important role these injuries play in the development and progression of kidney disease in type 2 diabetes, just as they do in type 1 diabetes. Whether podocyte detachment creates conduits for proteins to escape the glomerular circulation and reduced endothelial fenestration lowers glomerular hydraulic permeability requires further study.
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DOI：
10.1152/ajprenal.90601.2008
发表时间：
2009-05
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Satchell SC;Braet F
通讯作者：
Braet F
影响因子：
16.2
作者：
MacIsaac, R;Tsalamandris, C;Jerums, G
通讯作者：
Jerums, G
影响因子：
8.2
作者：
NELSON, RG;NEWMAN, JM;BENNETT, PH
通讯作者：
BENNETT, PH
影响因子：
158.5
作者：
Eremina, Vera;Jefferson, J. Ashley;Quaggin, Susan E.
通讯作者：
Quaggin, Susan E.
影响因子：
19.6
作者：
Lemley, KV;Abdullah, I;Nelson, RG
通讯作者：
Nelson, RG