Apoptosis in the kidneys of patients with type II diabetic nephropathy

Apoptosis in the kidneys of patients with type II diabetic nephropathy
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DOI:
10.1038/sj.ki.5002531
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发表时间:
2007-11-01
影响因子:
19.6
通讯作者:
Garibotto, G.
Garibotto, G.
中科院分区:
医学1区
文献类型:
--
作者:
Verzola, D.;Gandolfo, M. T.;Garibotto, G.

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糖尿病肾病患者肾脏细胞凋亡的发生和程度尚不清楚。我们评估了从早期或晚期 II 型糖尿病肾病患者获得的肾活检中的细胞凋亡。早期肾病患者肾脏的肾小球和肾小管的细胞凋亡分别比正常肾脏高 6 倍和 3 倍,而在晚期糖尿病肾病中这种情况并没有进一步增加。肾小球细胞凋亡与血红蛋白 A1(c) 和收缩压直接相关,而肾小管细胞凋亡与糖尿病病程和低密度脂蛋白胆固醇相关。肾小球和肾小管中 Fas、Fas 配体和 p38 丝裂原激活蛋白激酶的表达增强;然而,这与细胞凋亡无关。在蛋白尿患者中,细胞凋亡与随后的肾功能丧失相关。当对这些参数进行多变量分析时,只有肾小球细胞凋亡保留了显着的独立预测值。我们的研究结果表明,细胞凋亡可能是蛋白尿 II 型糖尿病患者肾小球和肾小管细胞损失的临床相关机制。
The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1(c) and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein-cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.