15例轻链型淀粉样变性患者肾组织病理误诊分析

Analysis of renal pathological misdiagnosis in 15 patients with light chain amyloidosis

目的:分析15例首次肾活检诊断为其他肾脏疾病的轻链型淀粉样变性患者的临床病理资料,以期寻找可能的误诊原因。方法:该研究为回顾性观察研究。收集2010年1月至2022年12月在北京大学第一医院肾内科住院的首次肾活检未诊断轻链型淀粉样变性、经重复肾活检或病理会诊诊断为轻链型淀粉样变性15例患者的临床和病理资料,分析2次肾活检的免疫荧光、刚果红染色和电镜检查结果。结果:15例患者中位年龄为56岁,男女比例为7∶8,临床主要表现为肾功能正常的大量蛋白尿,肾病综合征10例。首次肾活检诊断分别为微小病变肾病(8例)、IgA肾病(3例)、膜性肾病(3例)及Ⅲ型胶原肾小球病(1例)。首次肾活检时13例患者未评估血M蛋白血症,12例未行肾组织免疫荧光轻链检查,13例未行刚果红染色。首次肾活检后15例患者均接受了糖皮质激素联合免疫抑制剂治疗,重度感染5例。治疗时间为12.0(7.5,20.0)个月,15例患者均未达到临床缓解。重复肾活检前13例患者检测出M蛋白血症。所有患者重复肾活检肾组织均行免疫荧光轻链检查、刚果红染色,必要时行免疫电镜检查。14例患者重复肾活检及1例病理会诊结果均提示淀粉样变性,11例肾组织免疫荧光及2例肾组织免疫电镜可见轻链限制性表达。除1例失访14例患者均接受了靶向浆细胞治疗,获得血液学缓解6例,获得肾脏缓解5例,进入终末期肾病1例,死亡3例。结论:中老年肾病综合征患者如常规免疫抑制治疗效果不佳,应重视寻找单克隆免疫球蛋白血症证据,必要时需积极进行重复肾活检。肾活检病理检查应包括完整的免疫荧光轻链、刚果红染色和电镜检查,避免轻链型淀粉样变性的误诊。

Objective To analyze the clinical and pathological data of 15 patients with light chain amyloidosis initially diagnosed with other kidney diseases,and identify possible misdiagnosis reasons.Methods It was a retrospective observational study.The clinical and pathological data of 15 patients,whose initial kidney biopsies failed to diagnose light chain-amyloidosis but were confirmed by a subsequent kidney biopsy or pathology consultation at Peking University First Hospital from January 2010 to December 2022 were collected.The results of immunofluorescence,Congo red staining,and electron microscopy of two renal biopsies were analyzed.Results The median age of 15 patients was 56 years old,with a male-to-female ratio of 7∶8.The main clinical manifestation was massive proteinuria with normal kidney function,and there were 10 cases presenting as nephrotic syndrome.The initial diagnosis based on the first kidney biopsy included minimal change disease(8 cases),IgA nephropathy(3 cases),membranous nephropathy(3 cases),and typeⅢcollagen glomerulonephritis(1 case).M proteinemia was not evaluated in 13 patients during the first kidney biopsy.Light chain immunofluorescence staining was not performed in 12 cases.Congo red staining was not performed in 13 cases.All fifteen patients received glucocorticoids combined with immunosuppressive therapy after their initial diagnosis,and 5 patients developed severe infection.After 12.0(7.5,20.0)months of treatment,none of them achieved clinical remission.Thirteen had evidences for M protein before the second kidney biopsy.The renal tissues of all patients underwent immunofluorescence light chain examination,Congo red staining,and immunoelectron microscopy examination when necessary.The repeat kidney biopsies of 14 cases and pathology consultation of one case consistently indicated light chain-amyloidosis.The kidney tissues in 13 cases were confirmed to be light chain restricted,11 cases by immunofluorescence,and 2 cases by immune electron microscopy.After diagnosis of light chain-amyloidosis,all patients received targeted plasma cell therapy except for 1 patient lost to follow-up,6 patients achieved hematologic remission,5 patients achieved renal remission,1 patient entered end-stage renal disease,and 3 patients died.Conclusions In middle and elderly-aged patients with nephrotic syndrome,if conventional immunosuppressive therapy yields unsatisfactory results,it is crucial to focus on identifying evidences of monoclonal immunoglobulinemia,if necessary,kidney biopsy should be actively repeated.Kidney biopsy pathology should include comprehensive examinations such as light chain immunofluorescence,Congo red staining,and electron microscopy to avoid misdiagnosis of light chain-amyloidosis.