肾小球上皮细胞增生病变在局灶节段性肾小球硬化症中的临床意义及其组织来源探讨

Clinical significance and histological origin of glomerular epithelial proliferative lesion in patients with focal segmental glomerulosclerosis

目的探讨特发性局灶节段性肾小球硬化症（FSGS）的肾小球上皮细胞增生病变（glomerular epithelial proliferative lesion, GEPL）的临床意义及其组织学来源。方法2000年1月至2005年12月间在本研究所接受治疗的特发性FSGS患者共74例，按照是否存在GEPL病变分为两组：GEPL组31例，非GEPL组43例。分析两组患者的临床病理特点，对其活动性及慢性化病理改变进行半定量评估，并对患者的治疗和预后进行随访。通过免疫组化方法分析肾小球增生上皮细胞的细胞表型表达情况。结果与非GEPL组相比，GEPL组的病程显著较短（P〈0．05）；肾病综合征（NS）患者比例显著较高（P〈0．05）；节段性硬化的肾小球比例显著较高（P〈0．05）；病理活动性评分显著较高（P〈0．05）；慢性化评分显著较低（P〈0．05）。29例随访患者中，GEPL组（16例）的肾脏存活率明显降低（P=0．049）。COX回归分析发现GEPL和Scr水平是导致肾衰竭的危险因素（OR值分别为1．204和1．008）。免疫组化结果显示肾小球增生上皮细胞WT-1及Pcx表达缺失；细胞增殖核抗原（PCNA）、Pax-2和CK-8表达阳性。结论特发性FSGS的肾小球上皮细胞增生病变是急性期、活动性病变的病理表现，也可能为临床病情较重和肾脏存活预后不良的病理学指征。增生的肾小球上皮细胞缺乏足细胞表型，说明可能源于壁层上皮细胞，但不排除损伤的足细胞去分化、增生并表达壁层上皮细胞标记的可能。

Objective To investigate the clinical significance and histological origin of glomerular epithelial proliferative lesion in patients with focal segmental glomcrulosclerosis （FSGS）. Methods Seventy-four patients with idiopathic FSGS hospitalized in Peking University First Hospital from Jan. 2000 to Dec.2005 were enrolled in this study. Patients were classified into two groups according to with or without glomerular epithelial proliferative lesion. Estimation of active and chronic pathological scores was carried out using a semi-quantitative grade system by two pathologists. Clinical and pathological characteristics were compared between two groups. Immunohistochemical studies were performed to analyze the histological origin of glomerular epithelial proliferative lesion. Results Thirty-one patients with glomerular epithelial proliferative lesion showed shorter interval from presentation to biopsy （P〈0.05）, higher percentage of nephrotic syndrome （NS） （P〈0.05）, higher frequency of segmental glomerulosclerosis （P〈0.05）,higher pathological active scores （P〈0.05） and lower pathological chronic scores （P 〈0.05 ）as compared to 43 patients without glomerular epithelial proliferative lesion. Twenty-nine patients were followed up and renal survival rate in patients with glomerular epithelial proliferative lesion （39.7%） was significantly lower than that in patients without glomerular epithelial proliferative lesion （83.3%） （P=0.049）. The frequency of glomerular epithelial proliferative lesion and the serum creatinine （Scr） level at biopsy were independent predictors of ESRD （OR value was 1.204,1.008 respectively）. Glomerular epithelial proliferative lesion did not express mature podocyte markers including WT-1 and podocalyxin, but stained positive for PCNA, PAX-2 and CK-8. Conclusions Glomerular epithelial proliferative lesion represents the pathological change of acute stage and active lesion of FSGS, and also may be the pathological marker of severe clinical presentation and worse renal survival. Glomerular epithelial proliferative lesion may be derived from proliferation of parietal epithelial proliferation or de-differentiated podocytes.