合并肾损害的抗中性粒细胞胞浆抗体相关性血管炎患者的临床特点、治疗及预后研究

Clinical Characteristics,Treatment,and Prognosis of ANCA-associated Vasculitis in Patients with Renal Injury

目的 分析合并抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）患者的临床特点、治疗及预后.方法 选择2004年4月-2011年4月在我院肾内科确诊的有肾损害的43例AAV患者,回顾性分析其临床、病理、实验室检查等指标及治疗情况,并进行前瞻性随访.结果 （1）43例患者发病到确诊的中位时间为6个月,1个月内确诊者10例（23%）.确诊后Birmingham积分：12～26分,平均（18.7±3.9）分.临床分型：早期血管炎型7例,全身型21例,重度肾损害型15例.行肾活检病理检查者16例,其中局灶型3例,新月体型8例,混合型4例,硬化型1例.（2）本组患者死亡21例（51%）,死亡时间发生在确诊后第1～44个月,平均（10.9±11.6）个月,第1年死亡14例（67%）.感染为死亡的首要原因（12/21,57.1%）.（3）Kaplan-Meier生存曲线显示,本组患者确诊后1年生存率为66%,5年生存率为42%,总体中位生存时间为（29.0±12.7）个月.年龄≥65岁患者的生存率低于年龄＜65岁患者（P=0.000）;确诊时Scr＜125 μmol/L患者的生存率最高,Scr≥500 μmol/L患者的生存率最低（P=0.021）;欧洲血管炎研究组（EUVAS）不同临床分型患者的生存率比较,早期血管炎型＞全身型＞重度肾损害型.确诊时肺部CT提示有间质性肺病患者的生存率低于无间质性肺病患者（P=0.000）.（4）生存分析显示年龄≥65岁患者的肾存活率低于年龄＜65岁患者（P=0.000）;确诊时Scr≥500 μmol/L患者的肾存活率低于Scr＜500 μmol/L患者（P=0.027）;重度肾损害型患者的肾存活率低于早期血管炎型和全身型患者（P=0.000）.对行肾活检病理检查的16例患者进行初步分析,硬化型肾存活最差,其次为新月体型,局灶型和混合型肾存活最好（P=0.001）.（5）建立Cox比例风险模型,结果仅有确诊时年龄是预后不良的独立危险因素.结论 AAV患者确诊时高龄和血肌酐升高是影响肾存活和生存率的重要因素.虽然提高早期确诊率可以使患者得到早期治疗和病情监测,但是需要重视治疗带来的并发症,特别是感染对AAV患者生存率的影响.

Objective To analyze the treatment and prognosis of anti - neutrophil cytoplasmic antibody （ANCA） associated vasculitis （AAV） in patients with renal injury. Methods There were 43 patients of AAV with renal injury diagnosed in Department of Nephrology in Guang＇anmen Hospital from April 2004 to April 2011 included in our study. The clinical charac- teristics, pathological and laboratory indexes, and the treatment, the prognosis were retrospectively analyzed. Results The median time of the 43 patients from onset to diagnosis was 6 months, among which 10 cases were diagnosed in 1 month. The Bir- mingham Vasculitis Activity Scores （BVAS） ranged from 12 to 26, with an average of （ 18. 7 ＋ 3.9）. The clinical classifica- tion： early systemic vasculitis 7 cases, generalized vasculitis 21 cases, severe renal vasculitis 15 cases. There were 16 cases with renal biopsy, pathological classification including： focal 3 cases, crescentic 8 cases, mixed 4 cases, sclerotic 1 case. There were still 21 deaths among the rest 39 cases; The time from diagnosis to death ranged from 1 month to 44 months with an average of （ 10. 9 ± 11.6） months, among which 14 cases （67%） died in one year after diagnosis. Infection was the first cause （12/21, 57. 1% ）. The Kaplan -Meier survival analysis demonstrates that： the one -year patient survival rate after di- agnosis was 66%, while the five -year survival rate was 42%. The overall median survival time was （29.0 ± 12. 7） months. Survival rate of the group aged 65y was significantly lower than that of the group aged 〈 65y （P = 0. 000） ; The survival rate of the group with Scr 〈 125 μmol/L at diagnosis was significantly higher than those of the other groups, in which survival rate in the group with Scr ≥500 μmol/L was the lowest （P =0. 021 ） ; The survival rate in early systemic vasculitis group as classified by EUVAS was highest followed by the generalized vasculitis group, and severe renal vasculitis group. The survival rate of the group with interstitial lung disease at diagnosis was significantly lower than the group without interstitial lung disease （P = 0. 000）. The survival analysis showed that the renal survival rate of the group aged ~65y was lower than that of the group aged 65 years （P = 0. 000） ; The renal survival rate in the group with Scr≥500μmol/1 at diagnosis was lower than that of the group with Scr 〈500 μmol/L （ P = 0. 027 ） ; The renal survival rate of the patients with severe renal vasculitis was lower than those of the patients with early systemic vasculitis and generalized vasculitis （P = 0. 000）. Preliminary analysis of the 16 cases with renal pathological data demonstrated that renal survival rate of patients with sclerotic lesion was the lowest; The two - year renal survival rate of the pa- tients with crescentic lesion was lower; The renal survival rate of the patients with focal lesion and mixed lesion was the highest （ P = 0. 001 ）. The Cox proportional hazard model showed that age at diagnosis was the independent dangerous factor for the prog- nosis. Conclusion Age and increased level of Scr at diagnosis of AAV are the important factors influencing the renal survival and the survival rate. The early diagnosis could facilitate early treatment and surveillance, however, we should pay more atten- tion to the complications of the treatment, especially infections.