抗肾小球基底膜病临床病理及血浆置换疗效分析

Analysis of clinicopathology and plasmapheresis efficacy in patients with anti-glomerular basement membrane disease

目的分析抗肾小球基底膜（GBM）病的临床病理特点和预后；评价双膜血浆置换（DFPP）清除抗GBM抗体的有效性和安全性。方法回顾分析北京协和医院1999年10月至2010年5月确诊为抗GBM病的35例住院患者的临床病理资料。患者根据临床表现分为3组：组Ⅰ：24例严重肺出血或急进型肾小球肾炎（RPGN）者，接受甲泼尼龙（7．5～15mg·kg^-1·d^-1，3～5d）冲击和（或）DFPP治疗，后续以泼尼松（1．0mg·kg^-1·d^-1）和（或）环磷酰胺（CTX0．1g／d）；组Ⅱ：5例无严重肺出血或RPGN者予泼尼松和（或）CTX治疗；组Ⅲ：5例就诊时已为终末期肾病（ESRD）和1例肾功能正常者未给予免疫抑制治疗。观察患者临床病理特点，连续监测4例患者DFPP治疗前后抗GBM抗体滴度变化情况，计算抗体的清除率。分析影响预后的相关因素。结果35例患者平均年龄（41．06±16．55）岁，男女比例4：3；16例（45．7％）患者表现为Goodpasture综合征；18例（51．4％）表现为抗GBM肾小球肾炎。24例接受肾穿刺活检患者中，13例（54．2％）表现为新月体肾小球肾炎；7例患者并发其他肾小球肾炎。组Ⅰ死亡7例，50％患者肾脏长期存活。与组Ⅱ相比，组I患者人院时Scr水平、抗GBM抗体滴度、肾小球新月体比例均显著升高（P〈0．05）；老年患者、贫血、入院时Scr水平高（〉300μmol／L）及硬化肾小球比例更高；入院时少尿或无尿、需要血液透析治疗、肾脏预后差更普遍。18例患者的94次DFPP治疗中，无明显出血、低血压；4例连续动态监测抗GBM抗体滴度的患者中，4-6次DFPP后抗GBM抗体转阴，中位清除率为55％。结论根据不同临床表现选择个体化的治疗方案有助于改善预后，减少并发症。DFPP能安全有效地清除抗GBM抗体。

Objective To analyze the elinicopathological features and prognosis of anti- glomerular basement membrane （GBM） disease, and evaluate the efficacy and safety of double filtration plasmapheresis （DFPP）. Methods A total of 35 hospitalized patients diagnosed as anti-GBM disease in our department were enrolled in the study. All the patients were divided into 3 groups according to the manifestations at admission. Group I ： 24 patients with severe puhnonary hemorrbage or rapidly progressive glomerulonephritis （RPGN） received pulse methylprednisolone with or without DFPP, and then followed by prednisone and CTX. Group II ： 5 patients without severe pulmonary hemoRRhage and RPGN received prednisone and CTX. Group III： 5 ESRD patients and 1 normal renal function patient did not receive immunosuppression therapy. Anti-GBM antibody titer of pre- and post-DFPP in 4 patients was measured consecutively, and removal rate was calculated. Results The mean age of all the patients was （41.1±16.6） years. Sixteen patients （45.7%） presented Goodpasture＇s syndrome. Eighteen patients （51.4%） had anti-GBM glomerulonephritis alone, whereas one suffered solely from pulmonary hemorrhage. 20% patients had positive P-ANCA serology. 54.2% crescentic glomerulonephritis and 7 with other glomerulonephritis were revealed by kidney biopsy in 24 patients. Patients in Group I showed more severe manifestation at admission： higher Scr level, higher titer of anit-GBM antibody, greater percentage of crescents. Within the follow-up period, 7 patients died and kidneys of 50% patients survived. No patient died in Group III and III. The elder age, anemia, higher Scr （〉300 μmol/L）, oliguria or anuria, emergency hemodialysis at admission, and more glomerular sclerosis were predictors of poor prognosis. The anti-GBM antibody was negative after 4 to 6 sessions of DFPP, and the mean removal rate was 55%. During total 94 DFPP sessions, there was no unacceptable morbidity. Conclusions Different therapy strategy is necessary for anti-GBM disease with different clinical manifestations. DFPP is an effective and safe clearance way of anti-GBM antibody.