糖尿病肾病肾小球滤过膜超微结构改变及其与蛋白尿的关系

目的:观察2型糖尿病肾病(2TDN)患者肾小球滤过膜超微结构变化特点及与蛋白尿的关系。方法:将明确诊断的2TDN患者分为微量白蛋白尿组(尿白蛋白/24h30～300mg);蛋白尿组(尿蛋白0.5～2.0g/24h)和大量蛋白尿组(尿蛋白>3.5g/24h)。收集三组患者临床指标,并分别观察各组患者肾活检组织学及肾小球滤过膜超微结构变化,采用形态学计量分析方法分别测算肾小球体积、肾小球足细胞和内皮细胞的相对密度、绝对数目和足细胞足突宽度及肾小球基膜(GBM)厚度。结果:三组患者的年龄、性别、BMI、血压和糖尿病及肾脏病病程均无统计学差异。2TDN患者肾组织超微结构定量分析结果证实:(1)2TDN患者在微量白蛋白尿期肾小球毛细血管袢内皮细胞数目就已增加(实验组vs对照组P<0.01),内皮细胞相对密度则维持在一定水平(各组间P>0.05);(2)GBM改变包括三层结构消失、GBM增厚等,这些改变在微量白蛋白尿期就已发生,且GBM与病程密切相关(蛋白尿组,r=0.538,P<0.05)。(3)微量白蛋白尿组患者肾小球足细胞相对密度下降(微量白蛋白尿组vs对照组P<0.01)、足细胞足突宽度增加(微量白蛋白尿组vs对照组P<0.05)。随病程进展,足细胞相对密度和绝对数目呈进行性减少(微量白蛋白尿组vs大量蛋白尿组P<0.05)。(4)2TDN患者蛋白尿水平与肾小球足细胞数目(大量蛋白尿组,r=0.648,P<0.01)及GBM厚度(蛋白尿组,r=0.538,P<0.05)相关。结论:DN患者肾小球滤过膜超微结构发生了系列变化,这些变化与蛋白尿的发生、发展有着内在联系。

Relationship between ultrastructural changes of glomerular filtration barrier and proteinuria in patients with type 2 diabetic nephropathy

Objective:To examine the ultrastructural changes of glomerular filtration barrier in patients with type 2 diabetic nephropathy (2TDN) and to explore the relationship between the ultrastructural changes and proteinuria. Methodology:Fifty cases with type 2 DN were enrolled in this study. According to urinary protein excretion they were divided into three groups:microalbuminuria (albuminuria 30~300 mg/24h),overtproteinuria (proteinuria 0.5-2.0 g/24h) and heavyproteinuria (proteinuria>3.5 g/24h). The clinical parameters were collected,and renal biopsy were performed in all patients. The histological characteristics and the changes of glomerular filtration barrier were observed under light microscope and transmission electron microscope. The glomerular volume,endotheliocyte density,endotheliocyte number,GBM thickness,podocyte density,podocyte number and foot-process width in the three groups of patients were also analyzed by morphometric methods. Results:There was no significant difference in age,sex,BMI,blood pressure,duration of DN among three different groups. We found that the changes of glomerular filtration barrier were swelling,proliferation and the detachment from GBM of the glomerular endothelial cells,wrinkling,collapse GBM,the changes of GBM thickness,the density and disappearance of normal trilaminar structure,the different degrees of foot-process fusion,microvillus formation,and the defluvium of podocyte. The morphometry analysis under light-and electron-microscopic were confirmed:(1) The number of glomerular endothelial cells had already increased in patients with 2TDN since the stage of microalbuminuria (microalbuminuria,overtproteinuria,heavyproteinuria vs control P<0.01),but the density of glomerular endothelial cells didn't change much among three different proteinuria groups (P>0.05). (2) The thickness of GBM increased since the stage of microalbuminuria (microalbuminuria,overtproteinuria,heavyproteinuria vs control P<0.01),and more disappearance of normal trilaminar structure occured as the proteinuria increasing. (3) Since the stage of microalbuminuria,the density of podocyte was decreased (microalbuminuria vs control P<0.01),and foot-process width was increased (microalbuminuria vs control P<0.01). With the development of disease,the podocyte density and number was progresively decreased (microalbuminuria vs heavyproteinuria P<0.05). (4) The degrees of proteinuria was related to the number of podocyte (heavyproteinuria,r=0.648,P<0.01) and GBM thickness (overtproteinuria,r=0.538,P<0.05). Conclusion:There was a series of changes in the ultrastructure of glomerular filtration barrier in patients with 2TDN,which were corelative with proteinuria.