移植肾单克隆IgG相关的增生性肾小球肾炎临床病理特点及预后

Proliferative glomerulonephritis with monoclonal IgG deposits in renal allografts： clinicopathologic features and prognosis

目的总结分析移植肾单克隆IgG相关的增生性肾小球肾炎（PGNMID）的临床病理特点、治疗和预后。方法通过电子病历系统搜集南京总医院2008年1月至2017年4月间收治的诊断为PGNMID的肾移植受者资料，总结其临床病理特点、治疗和转归。结果共有5例患者入选，临床上表现为蛋白尿（5例）、血肌酐升高（4例）或血尿（4例），临床症状出现时间在肾移植后5-19个月。光镜下移植肾病理表现形态各异，大部分表现为膜增生改变，而在早期可以仅表现为轻度系膜增生。免疫荧光检查分类显示，3例患者为单克隆IgG3κ沉积，另2例患者IgG3λ阳性。1例患者光镜下移植肾病理表现基本正常，免疫荧光检查显示有IgG沉积，需要行IgG亚型检查和轻链染色，以助诊断PGNMID。5例中4例患者接受利妥昔单抗和硼替佐米治疗，治疗后蛋白尿均有不同程度减轻，仅2例患者血肌酐水平经治后下降。最后随访中，1例患者已恢复透析治疗，另有2例患者血肌酐〉265.2 μmol/L。结论PGNMID光镜下主要表现为膜增生样改变，IgG3是最常见的亚型。PGNMID肾移植术后很快就会复发。利妥昔单抗和硼替佐米治疗有益于降低蛋白尿水平，但是其降肌酐的疗效不肯定。移植肾PGNMID最佳治疗方案仍有待大样本研究证实。

Objective To characterize the clinicopathologic features, treatment efficacy and prognoses of proliferative glomerulonephritis with monoclonal IgG deposits （PGNMID） in renal allografts. Methods Electronic medical records of Jinling Hospital were searched for PGNMID that was diagnosed during January 2008 to April 2017. Clinicopathologic features, treatment regimens and prognoses information were retrieved and analyzed. Results We identified 5 cases of PGNMID with clinical symptoms of proteinuria （5/5）, serum creatinine elevation （4/5） or hematuria （4/5） 5 to 19 months after kidney transplantation. Various light microscopic features were observed, with predominantly membranoprolifeative pattern. Mild mesangial proliferation pattern could be observed in early stages of disease progression. Immunofluorescence revealed monoclonal IgG3κ in 3 patients and IgG3κ in another 2 cases. One case of PGNMID with normal light microscopy but monoclonal IgG deposits was verified by IgG and light-chain subtyping. In the 4 patients treated with rituximab or bortezomib, decreased proteinuria was achieved in all treated patients while the decreases in serum creatinine decrease were only observed in 2 patients. At last follow-up, one patient was in dialysis and serum creatinine levels of other 2 patients were 〉265. 2 μmol/L. Conclusion Membranoprolifeative pattern is the most frequently observed microscopic findings and IgG3 is the most frequent IgG subtype in PGNMID. PGNMID recurs shortly after kidney transplantation. Rituximab and/or bortezomib is conducive to decrease proteinuria while their efficacy to decrease serum creatinine is dubious. The most effective treatment protocol for PGNMID remains to be determined in larger samples.