肾脏轻链沉积病合并管型肾病的临床病理特点

目的探讨轻链沉积病合并管型肾病(LCDD&LCN)的临床病理特点。方法选择2000年1月至2018年3月在北京大学第一医院肾内科经肾活检确诊的10例LCDD&LCN患者为研究对象,以21例单纯轻链沉积病(I-LCDD)及17例单纯管型肾病(I-LCN)患者作为对照。所有病例均进行了光镜、免疫荧光(包括轻链)和电镜检查,并对肾脏病理主要特点进行半定量评估。回顾性分析LCDD&LCN患者的临床病理资料。结果 LCDD&LCN多发于中年男性,9例表现为急性肾功能不全,伴有大量(占97.1%)小分子为主的尿蛋白及镜下血尿,9例符合多发性骨髓瘤,血尿单克隆轻链λ型占5/8。肾脏病理显示肾小球系膜细胞和基质轻度增生,仅1例可见系膜结节状硬化,同时可见急性肾小管损伤伴轻链蛋白管型,其临床表现及光镜所见与I-LCN相似。免疫荧光可见单克隆轻链沿肾小球基底膜(GBM)、肾小管基底膜(TBM)及鲍曼囊壁等呈线样沉积,也可见于管型;电镜见GBM内侧、TBM外侧以及肾间质或血管壁等存在粉末状、沙砾样电子致密物沉积。结论 LCDD&LCN以急性肾功能不全为突出表现,多数合并多发性骨髓瘤,病理特征兼具LCDD和LCN的病理特点,其诊断依赖于轻链的免疫荧光和电镜检查。

Clinicopathological characteristics of renal light chain deposition disease coexisted with cast nephropathy

Objective To investigate the clinicopathological characteristics of renal light chain deposition disease coexisted with cast nephropathy (LCDD&LCN). Methods Patients with LCDD&LCN (n=10), isolated LCDD (I-LCDD, n=21) and isolated LCN(I-LCN, n=17) diagnosed by renal biopsy in Peking University First Hospital from January 1, 2000 to March 31, 2018 were enrolled, and all cases were examined by light microscopy, immunofluorescence (IF) (including light chain) and electron microscopy (EM). The semi-quantitative evaluation of the main features of renal pathology was performed. The clinical manifestations and pathological features were reviewed and compared. Results LCDD&LCN was more prevalent in middle-aged males. Nine patients showed acute renal insufficiency with small molecular proteinuria (97.1%) and microscopic hematuria. The hematologic diseases included 9 patients of multiple myeloma. The type of monoclonal light chain in serum and urine by immunofixation electrophoresis showed λ dominant (5/8). By light microscopy, glomerular lesions presented with mild mesangial proliferation in most patients, and only one of them displayed mesangial nodular sclerosis. At the same time, acute tubular injury with light chain casts was the prominent feature, and the clinical manifestations and histological features of LCDD&LCN were similar to that of I-LCN. IF revealed linear staining of monoclonal light chain along the glomerular basement membrane (GBM), tubular basement membrane (TBM) and Bowman's capsule, and also positive in tubular casts. By electron microscopy, diffuse powder-like or granular electron-dense deposits located in the inner side of the GBM, the outer layer of the TBM, renal interstitium and arteriolar walls were observed. Conclusions Patients with LCDD&LCN manifest as acute renal insufficiency, and the majority have multiple myeloma. The pathology of LCDD&LCN possesses the features of both I-LCDD and I-LCN. The IF stain of light chains(κ, λ) and ultrastructural examination by electron microscopy are the inevitable methods for the diagnosis of LCDD&LCN.