Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes
Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes
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DOI：
10.2337/diabetes.52.4.1031
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发表时间：
2003-04-01
期刊：
影响因子：
7.7
通讯作者：
Fioretto, P
中科院分区：
文献类型：
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作者：
Dalla Vestra, M;Masiero, A;Fioretto, P
足细胞结构的改变被认为与糖尿病蛋白尿的发病机制有关。我们评估了67例白色2型糖尿病患者的足细胞密度、数量和结构：21例正常白蛋白尿（NA）、23例微量白蛋白尿（MA）和23例蛋白尿（P）。进行肾功能和活检研究; 20名肾脏供体作为对照受试者。电子显微镜形态测定分析用于估计每个肾小球的足细胞数密度[Nv（epi/glom）]、每个肾小球的滤过缝长度密度（FSLv/glom）和足突宽度（FPW）。通过将Nv（epi/glom）乘以平均肾小球体积获得每个肾小球的足细胞数（Epi N/glom）。Nv（epi/glom）在所有2型糖尿病组均显著低于对照组，MA和P组低于NA组（P < 0.0001，ANOVA）。MA组和P组Epi N/glom均低于对照组（P < 0.002，ANOVA），但2型糖尿病组间差异无统计学意义。此外，MA和P降低了FSLv/glom。与NA相比，FPW增加（均P < 0.005，ANOVA）。白蛋白排泄率与Nv（epi/glom）和FSLv/glom呈负相关，与FPW呈正相关（均P < 0.0005），而与Epi N/glom无相关性。总之，足细胞结构和密度的变化发生在糖尿病肾病的早期阶段，可能有助于增加2型糖尿病患者的白蛋白尿。这些发现还表明，在白色2型糖尿病患者中，足细胞的密度可能比绝对数量在功能上更相关。
Podocyte structural changes have been suggested to be involved in the pathogenesis of albuminuria, in diabetes. We evaluated podocytes density, number, and structure in 67 white patients with type 2 diabetes: 21 normoalbuminuric (NA), 23 microalbuminuric (MA), and 23 proteinuric (P). Kidney function and biopsy studies were performed; 20 kidney donors served as control subjects. Electron microscopic morphometric analysis was used to estimate numerical density of podocytes per glomerulus [Nv(epi/glom)], filtration slit length density per glomerulus (FSLv/glom), and foot process width (FPW). The number of podocytes per glomerulus (Epi N/glom) was obtained by multiplying Nv(epi/glom) by mean glomerular volume. Nv(epi/glom) was significantly decreased in all type 2 diabetic groups compared with control subjects and was lower in MA and P than in NA (P < 0.0001, ANOVA). Epi N/glom was lower in MA and P patients compared with control subjects (P < 0.002, ANOVA); however, there were no significant differences among the type 2 diabetic groups. In addition, MA and P had decreased FSLv/glom. and increased FPW compared with NA (P < 0.005 for both, ANOVA). The albumin excretion rate was inversely related to Nv(epi/glom) and FSLv/glom and directly to FPW (P < 0.0005 for all), whereas there was no correlation with Epi N/glom. In conclusion, changes in podocyte structure and density occur since the early stages of diabetic nephropathy and might contribute to increasing albuminuria in type 2 diabetic patients. These findings also suggest that in white type 2 diabetic patients, the density of podocytes may be functionally more relevant than the absolute number.