ANCA相关性小血管炎肾损害的临床病理特征及预后分析

Clinical characteristics and prognosis of ANCA- associated vasculitis in patients with renal injury

目的分析抗中性粒细胞胞浆抗体（ANCA）相关性小血管炎（AAV）肾损害的临床病理特征及预后。方法选择武汉大学人民医院2012年1月至2017年1月期间确诊且合并肾损害的AAV患者，依据ANCA结果分为髓过氧物酶（MPO）-ANCA阳性和蛋白酶3（PR3）-ANCA阳性两组，分析比较两组的临床病理特征及预后。结果共纳入68例患者，其中MPO-ANCA阳性者52例（76．5％），PR3-ANCA阳性者16例（23．5％）；其中60岁以上者占60．3％。肾外累及器官主要为肺、消化和神经系统，差异有统计学意义（均P〈0．05）。实验室检查方面，血红蛋白、补体C3、补体Clq、IgE、24h尿蛋白定量、降钙素原、BVAS评分和eGFR的差异均具有统计学意义（均P〈0．05）。行肾活检病理检查19例，MPO．ANCA阳性者14例，PR3-ANCA阳性者5例。PR3．ANCA阳性者以纤维素样坏死和新月体形成为主，MPO—ANCA阳性者以肾小球硬化为主（均尸〈0．05）。平均随访32个月，随访6个月时MPO—ANCA阳性者和PR3．ANCA阳性者的肾脏复发率分别为46．2％和75．0％。多因素Logistic回归分析显示PR3．ANCA阳性、年龄≥65岁、基线eGFR〈30ml·min^-1·（1．73m^2）^-1、合并肺间质病变为影响患者疾病复发的独立危险因素。在随访期内，进入ESRD的比例分别为42．3％和75．0％；死亡10例。Cox回归分析显示年龄≥65岁、BVAS评分≥18分、eGFR〈30ml·min^-1·（1．73m^2）^-1、合并肺间质病变为患者进入ESRD和死亡的危险因素。结论PR3-ANCA阳性者比MPO—ANCA阳性者具有更严重的肾损害，肾外脏器受损也更严重，复发率更高，预后更差。

Objective To investigate the characteristics and outcome of anti- neutrophil cytoplasmic antibody （ANCA）- associated vasculitis （AAV） in patients with renal injury. Methods AAV patients with renal injury diagnosed in the Department of Nephrology, Renmin Hospital of Wuhan University, from January 2012 to January 2017 were included into this study. Patients were divided into MPO-ANCA positive and PR3- ANCA positive groups for further study. The clinical characteristics, pathological and laboratory indexes, treatment and prognosis were retrospectively analyzed. Results A total of 68 eases were enrolled, among which 52 cases （76.5%） were MPO-ANCA positive and 16 cases （23.5%） were PR3-ANCA positive, and 41 patients （60.3%） were over 65 years old. The incidences of interstitial lung disease, digestive and nervous system damage in PR3- ANCA positive group were significantly higher than those MPO- ANCA positive group （P 〈 0.05）. There were significant differences of hemoglobin, complement C3, complement Clq, IgE, 24 h urinary protein, erythrocyte sedimentation rate, procalcitonin, BVAS score and eGFR in two groups （P 〈 0.05）. 19 cases had done renal biopsy, among them 14 cases were MPO-ANCA positive and 5 cases were PR3-ANCA positive. Incidence of crescentic necrotizing glomerulonephritis in PR3- ANCA positive group was significantly higher than that in MPO- ANCA positive group, and incidence of diffuse global glomerulosclerosis in MPO- ANCA positive group was significantly higher than that in PR3- ANCA positive group （all P 〈 0.05）. At the median follow-up time of 32 months, the relapse rate at 6 month of MP0- ANCA- positive and PR3- ANCA- positive patients were 46.2% and 75.0%, respectively （P 〈 0.05）. Multivariate logistic regression analysis showed that PR3- ANCA positive, age~〉65 years old, baseline eGFR 〈 30 ml·min^-1·（1.73m^2）^-1, and combined with pulmonary interstitial lesions were all independent risk factors for relapse. And the incidence of ESRD were 42.3% and 75.0% during the follow- up period and 10 patients （14.7%） died. COX regression analysis showed that patients older than 65 years old, BVAS score~〉 18 points, eGFR 〈 30 ml ·min^-1·（1.73m^2）^-1 and complicated with pulmonary interstitial disorders at the onset were independent risk factors causing ESRD or death. Conclusion The PR3- ANCA-positive patients had more severe renal injury than those with MPO- ANCA- positive patients, and the injury of extrarenal organs was more serious, recurrence rate was higher, and the prognosis was worse.