Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy
Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy
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DOI：
10.2337/db07-0019
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发表时间：
2007-08-01
期刊：
影响因子：
7.7
通讯作者：
Mauer, Michael
中科院分区：
文献类型：
--
作者：
Toyoda, Masao;Najafian, Behzad;Mauer, Michael
本研究的目的是探讨糖尿病肾病足细胞和内皮细胞的结构特征。我们研究了18例1型糖尿病患者（7例蛋白尿正常，6例微量蛋白尿，5例蛋白尿）和6例正常对照。各组在年龄上没有差异。1型糖尿病组在糖尿病病程和发病年龄上没有差异。用形态计量学测量足细胞足突宽度（FPW）、肾小球基底膜（GBM）表面未脱离足突（IFP）的比例、有孔内皮覆盖的肾小球毛细血管管腔表面的比例[S-s(feneated /cap)]和典型糖尿病肾小球病变。同时测量白蛋白排泄（AER）和肾小球滤过（GFR）率。糖尿病患者GFR与GBM和肾小球系膜测量呈负相关，AER与之直接相关。FPW与GFR （r = -0.71, P = 0.001）呈负相关，与AER （r = 0.66, P = 0.003）、GBM和系膜参数直接相关。蛋白尿组与对照组（P = 0.001）、正常蛋白尿组（P = 0.0002）和微量蛋白尿组（P = 0.04）相比，IFP覆盖的GBM分数降低，并与肾结构和功能参数（包括AER）相关（r = -0.52, P = 0.03）。在蛋白尿患者中，只有78%的GBM被IFP覆盖。与对照组相比，正常蛋白尿（P 0.03）、微量蛋白尿（P = 0.03）和蛋白尿（P = 0.002）患者的S-s（feneated /cap）降低。S-s（开窗/帽）与肾小球系膜分数容积（r = -0.57, P = 0.01）、IFP （r = 0.61, P = 0.007）和FPW （r = -0.58, P = 0.01）相关。这些新研究证明足细胞脱离和内皮细胞开窗减少与1型糖尿病患者的典型糖尿病肾病病变和肾功能有关，并支持进一步研究足细胞/GBM粘附性和足细胞/内皮细胞功能相互作用在糖尿病肾病中的必要性。
The aim of this study was to investigate the structural characteristics of podocytes and endothelial cells in diabetic nephropathy. We studied 18 patients with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, and five proteinuric), and six normal control subjects. Groups were not different for age. Type 1 diabetic groups were not different for diabetes duration or age at diabetes onset. Podocyte foot process width (FPW), fraction of glomerular basement membrane (GBM) surface with intact nondetached foot processes (IFP), fraction of glomerular capillary luminal surface covered by fenestrated endothelium [S-s(Fenestrated/cap)] and classic diabetic glomerulopathy lesions were morphometrically measured. Albumin excretion (AER) and glomerular filtration (GFR) rates were also measured. GFR correlated inversely and AER directly with GBM and mesangial measurements in diabetic patients. FPW correlated inversely with GFR (r = -0.71, P = 0.001) and directly with AER (r = 0.66, P = 0.003), GBM, and mesangial parameters. The GBM fraction covered by IFP was decreased in proteinuric versus control subjects (P = 0.001), normoalbuminuric patients (P = 0.0002) and microalbuminuric patients (P = 0.04) and correlated with renal structural and functional parameters, including AER (r = -0.52, P = 0.03). Only 78% of GBM was covered by IFP in proteinuric patients. S-s(Fenestrated/cap) was reduced in normoalbuminuric (P 0.03), microalbuminuric (P = 0.03), and proteinuric (P = 0.002) patients versus control subjects. S-s(Fenestrated/cap) correlated with mesangial fractional volume per glomerulus (r = -0.57, P = 0.01), IFP (r = 0.61, P = 0.007), and FPW (r = -0.58, P = 0.01). These novel studies document that podocyte detachment and diminished endothelial cell fenestration are related to classical diabetic nephropathy lesions and renal function in type 1 diabetic patients and support a need for further studies of podocyte/GBM adherence and podocyte/endothelial cell functional interactions in diabetic nephropathy.