糖尿病肾病患者足细胞病变的临床病理特征

Glomerular podocyte lesion in patients with diabetic nephropathy

目的 :研究 2型糖尿病肾病患者肾小球足细胞病变 ,分析其与血糖控制、蛋白尿、肾功能及肾组织病理形态学改变之间的关系。 方法 :2 7例经肾穿刺活检明确诊断的 2型糖尿病肾病。肾组织病理定量计数肾小球足细胞数。借助足细胞特定标志物WT1与肾小球基膜Ⅳ型胶原α3链 (C Ⅳα3)双套色荧光染色 ,用激光共聚焦荧光显微镜对肾小球足细胞进行准确的密度定量分析。 结果 :糖尿病肾病患者无论临床表现为微量白蛋白尿、蛋白尿 (尿蛋白 <3 5g/ 2 4h) ,还是大量蛋白尿 (尿蛋白 >3 5g/ 2 4h) ,均伴肾小球足细胞数目及密度的减少 ,其中以大量蛋白尿组最为显著 ,蛋白尿组次之 ,微量白蛋白尿组最轻。足细胞数目及其密度与尿蛋白量呈显著负相关 (P<0 0 1)。足细胞数目的减少还与肾小球病理改变相关 ,表现为肾小球K W结节病变者其足细胞数明显少于肾小球弥漫系膜增生性病变者 (P <0 0 1)。此外 ,足细胞数减少严重者肾小球硬化以及血清肌酐水平升高的发生率均明显增高。 结论 :糖尿病肾病患者早期就表现出肾小球足细胞数目及其密度的减少 ,随着病变加重 ,这种变化愈发明显。足细胞病变不仅导致大量蛋白尿的发生 ,而且还与肾小球硬化和肾功能损伤的发生有关。

Objective:To examine the number and density of glomerular podocyte in patients with diabetic nephropathy and to explore the relationship between the podocyte lesion and proteinuria, renal histological changes as well as renal function Methodology:Twenty seven type 2 diabetic patients with biopsy proven diabetic nephropathy were used in this study The average number of podocyte per glomerulus was determined by dividing the total podocyte by the glomerular profile area as determined by point counting Immunmoflourescence double staining using anti WT1, a marker of podocyte, and anti type Ⅳ collagen a3 chain were performed to illustrate the structure of podocyte and glomerular basement membrane The stained sections were examined by the Confocal microscopy and the density of podocyte per glomerulus was calculated using specific software Results:Glomerular podocyte loss was observed in all of these patients The reduction was the most in patients with heavy proteinuria (>3 5 g/24h), patients with overt proteinuria (<3 5 g/24h) came second and than patients with microalbuminuria as compared with normal subjects There was a strong correlation between the podocyte loss and the degree of proteinuria ( P <0 01) In addition, patients with glomerular nodule lesion demonstrated much more podocyte loss than patients with diffuse mesangial proliferative change ( P <0 05) The frequencies of glomerulosclerosis and elevated serum creatinine level were also markedly increased in patients with significant reduction of podocyte Conclusion:The reduction in glomerular podocyte number was observed in the early stage of patients with diabetic nephropathy and become more dramatic during the course of disease progression The podocyte lesion not only associated with the degree of proteinuria, but also correlated with the development of glomerulosclerosis and renal function damage