轻链近端肾小管病的临床病理分析

Analysis of clinical and pathological manifestations of light chain proximal tubulopathy

目的探讨轻链近端。肾小管病（LCPT）的临床和病理特点。方法选择2011年1月至2016年9月在北京大学第一医院肾内科经肾活检确诊的9例LCPT患者为研究对象，所有病例均进行了光镜、常规免疫荧光、轻链免疫荧光和电镜检查，部分病例进行了轻链免疫电镜检查，回顾性分析LCPT患者临床病理资料。结果9例LCPT临床表现为小分子蛋白尿，伴急性或慢性肾功能不全，其中6例表现为完全性或不完全性范科尼综合征（Fanconi syndrome，FS）。9例LCPT的血液疾病诊断，6例为伴有肾脏损害的单克隆叫球蛋白病（MGRS），3例为多发性骨髓瘤（MM）。LCPT病理特征分为结晶型和非结晶型，其中7例为结晶型，均为．（型，光镜可见近端肾小管上皮胞质内空泡变性及针状结晶或裂隙样改变，电镜下可见菱形、矩形、棒状等形态的结晶；2例为非结晶型，均为入型，光镜可见肾小管上皮胞质有大量嗜银颗粒，均伴有管型。肾病，电镜下可见胞质内大量溶酶体颗粒，其中l例伴有轻链沉积病。免疫荧光可见肾小管上皮胞质内单种轻链阳性的颗粒分布，以石蜡切片酶处理后免疫荧光检查更为敏感；免疫电镜标记可见胞质内结晶或溶酶体被单种轻链特异标记。结论LCPT以继发性FS等近段肾小管功能受损为突出临床表现，病理以K型轻链导致的结晶型LCPT为主，非结晶型LCPT主要见于入型，且易合并管型肾病。LCPT的诊断依赖于电镜及轻链的免疫荧光和免疫电镜检查。

Objective To investigate the clinical and pathological characteristics of light chain proximal tubulopathy （LCPT）. Methods Nine patients with LCPT diagnosed by renal biopsy in Peking University First Hospital from January 1, 2011 to September 30, 2016 were enrolled, and their clinical findings and pathological features were reviewed. Immunofluorescence （IF） of light chains （κ, λ） on paraffin sections after protease digestion and immunogold labeling of light chains （κ, λ） on uhrathin sections were performed in some cases. Results The main clinical manifestation of the nine patients was proteinuria of small molecules, with acute or chronic renal insufficiency, and six of them led to partial or complete Fanconi syndrome （FS）. The hematologic diseases included 3 cases of multiple myeloma and 6 cases of monoclonal gammopathy of renal significance （MGRS）. Pathological examination of renal biopsy showed two types： crystalline and noncrystalline LCPT. Seven cases of crystalline LCPT were stained for κ light chain, the proximal tubular epithelial cytoplasm exhibited fine granular vacuolation, with needle- shaped crystals and clear clefts by light microscopy, the intracytoplasmic inclusions of various shapes including rhomboidal, rectangular and rod-shaped crystals were identified by electron microscopy. Two cases of noncrystalline LCPT were stained for k light chain, the prominent argyrophilic granules in cytoplasm of proximal tubular epithelia were observed by light microscopy, and intracytoplasmic large and irregular shaped phagolysosomes were found by electron microscopy, cast nephropathy were coexisted in these 2 cases, the additional light chain deposition disease were confirmed in one of them by electron microscopy and IF. All cases had monotypic staining of light chains in cytoplasm of proximal tubules by IF on frozen tissue and paraffin sections after protease digestion, with the latter method being more sensitive than the routine IF. The immunogold labeling showed specific monotypic labeling of κ and λ light chain on intracytoplasmic crystals and phagolysosomes respectively by immunoelectron microscopy. Conclusions LCPT is a rarely reported entity that manifested as acquired Fanconi syndrome and dysfunction of proximal tubules clinically. Pathologically it is divided into two types： crystalline and noncrystalline LCPT, with more prevalent of κ light chain related crystalline type, noncrystalline LCPT is mostly λ） type, and is easily coexisted with cast nephropathy. The IF and immunoelectron microscopy of light chains （κ, λ） and uhrastructural examination by electron microscopy are important methods for the diagnosis of LCPT.