足细胞损伤在预测肥胖相关性肾病发生中的价值

目的 研究肥胖相关性肾病患者肾小球足细胞病变,借助足细胞特异标记物Wilm肿瘤蛋白,分析其与蛋白尿、肾功能及肾组织病理形态学改变之间的关系.方法 15例经肾穿刺活检明确诊断的肥胖相关性肾痛.借助足细胞特异标记物采用免疫组织化学染色检查,对肾组织病理定量计数肾小球足细胞数.同时结合临床和肾组织病理有关指标的多因素进行分析.对照组5例,外科切除的且已诊断为肥胖的肾脏肿瘤标本的正常皮质组织.结果肥胖相关性肾病患者无论临床表现为小量蛋白尿组8例:24小时尿蛋白定量<1.0 g;中等量蛋白尿组4例:24小时尿蛋白定量1.0～3.5 g,大量蛋白尿组3例:24小时尿蛋白定量>3.5 g,与对照组比较肥胖相关性肾病患者均伴肾小球足细胞数目及密度的减少(均P<0.01),其中以大量蛋白尿组最为显著,中等量蛋白尿组次之,小量蛋白尿组最轻.足细胞数目及其密度与尿蛋白量呈显著负相关(r=0.664,P<0.01).足细胞数目的 减少还与肾小球病理改变相关,表现为肥胖相关性局灶节段性肾小球硬化症者其足细胞数目明显少于肥胖相关性肾小球肥大症者(P<0.01),足细胞融合、微绒毛化改变较多,肾小球硬化数明显增多(P<0.05).此外,足细胞数目减少严重者肾小球硬化(r=-0.427,P<0.05)以及血清肌酐水平升高的发生率均明显增高(r=-0.574,P<0.01).结论 肥胖相关性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,随着病变的加重,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.

Effect of glomerular podocyte lesion on obesity-related glomerulonephropathy

Objective To illustrate the structure of podocyte in the patients with obesity-related glomerulonephropathy by using anti-WT1(Wilm-tumor suppressor gene),a marker of podocyte and to explore the relationship between the podocyte lesion and proteinuria,renal histological changes as well as renal function.Methods The diagnosis was based on clinicopathological findings.Fifteen patients were enrolled.The average number of podocyte per glomerulus was determined using specific software.Biopsies from 5 obesity kidney donors at the time of transplantation provided comparative control data.Results Within the three groups,segmental loss of podocyte phenotype was noted.There was a marked reduction in the number of podocytes per glomerular tuft in patients with obesity-related glomerulonephropathy(P<0.01) than that in controls.The reduction was the most in patients with heavy proteinuria(>3.5 g/24 h),the patients with overt proteinuria(1.0-3.5 g/24 h) came second,and then patients with low proteinuria followed as compared with normal subjects.There was a strong negative correlation between the podocyte loss and the degree of proteinuria(r=-0.664,P<0.01).The result showed that the number of podocyte in the patients was associated with the glomerular histological changes,the patients with obesity-associated focal segmental glomerulosclerosis demonstrated much more podocyte loss than the patients with obesity-associated glomerulomegaly(P<0.01).The frequencies of glomerulosclerosis and elevated serum creatinine level were also markedly increased in the patients with significant reduction of podocyte as compared to controls(r=-0.574,P<0.01).Conclusion The reduction in glomerular podocyte number is observed in the early stage of the patients with obesity-related glomerulonephropathy and becomes more dramatic during the course of disease progression.The podocyte lesion is correlated with the development of glomerulosclerosis.The podocyte lesion is not only associated with the degree of proteinuria,but also correlated with the development of glomerulosclerosis and renal function damage.