丙基硫氧嘧啶相关血管炎肾损害的临床病理特征及转归

Clinic-pathological features and otcomes of patients with propylthiouracil-associated ANCA vasculitis

目的:回顾性分析丙基硫氧嘧啶(PTU)相关ANCA血管炎伴肾脏损害患者临床、病理特征及转归。方法:因Graves病或自身免疫性甲状腺炎引起甲状腺功能亢进,服用PTU后出现血清ANCA阳性伴肾脏损害患者12例[女性11例,男性1例,平均年龄(32.4±13.8)岁],均行肾活检病理检查和随访。回顾性分析患者的临床病理特征和转归。结果:12例患者服用PTU2～264月(中位时间42月),肾脏病程(11.5±20.1)月,ANCA类型均为P-ANCA,其中11例为MPO-ANCA阳性,1例MPO-/PR3-ANCA双阳性。临床均表现血尿(其中5例肉眼血尿)及蛋白尿[(1.9±1.6g/24h)],7例(58.3%)存在肾功能不全[SCr(282.88±335.92)μmol/L],其中3例入院时即需要肾脏替代治疗。肾活检病理10例为寡免疫复合物节段坏死性肾炎伴新月体形成,2例为节段坏死性肾炎伴膜性病变。治疗上均停用PTU并接受免疫抑制治疗,随访3～60月(中位时间19月),1例进入终末期肾衰,1例SCr倍增,2例转为慢性肾功能不全,8例完全缓解(肾功能正常,尿检阴性)。血清ANCA2例转阴,9例滴度下降,1例无变化。3例肾血管炎复发伴血清ANCA滴度升高。结论:本组PTU相关血管炎肾功能损害严重,病理改变除与ANCA相关的肾血管炎外,还合并膜性病变,预后不佳,停用PTU后ANCA持续阳性且滴度升高与复发相关,表明对ANCA水平升高者需维持免疫抑制治疗。

Objective：To retrospectively investigate the clinic-pathological features and outcomes of patients with propylthiouraeil （PTU）associated antineutrophil cytoplasmic autoantibody （ANCA） vasculitis with renal involvement. Methodology：Twelve patients [ 11 female and one male with average age of（ 32. 4± 13.8 ）years old ] treated with FFU and developed to ANCA positive and systemic vaseulitis with renal involvement were collected and analyzed. ANCA was detected by IF and ELISA. All patients had renal involvement and renal biopsy. Results：Of the 12 patients received FFU for 2 to 264 months （ median 42 too） , and the duration of renal disease was（ 11.5 -± 20. 1 ） months. All patients had serum positive ANCA, among them, 11 cases were MPO-ANCA positive, and one was MPO and PR3-ANCA double positive. All patients presented with hematuria and proteinuria, 5 had gross hematuria, the mean urine protein was （1.9 ± 1.6 ）g/24h, 7 had renal disfunetion, and 3 required initial renal replacement therapy. Renal biopsy showed pauei-immune necrotizing segmental crescentic glomerulonephritis in 10 cases, sand segmental neerotizing glomerulonephritis with membranous lesion in 2 cases. All patients withdrew PTU after the diagnosis and received immunosupressive therapy. Among them, l0 cases were followed -up for 13 to 57 months （median 26 mo） , one developed to ESRD, 2 patients progressed to chronic renal failure, and 7 patients were in completely remission （ normal renal function and urine analysis ）. Serum ANCA turned negative only in 2 patients, ten patients had persistent serum ANCA. 3 patients relapsed with the elevation of serum ANCA level. Conclusion：PTU-associated ANCA vaseulitis with renal involvement could be necrotizing crescentic glomerulonephritis, or superimposed on membranous lesion. The prognosis was not benign, most patients had persist positive serum ANCA and relapsed even after PTU withdraw. The prognosis was not benign because of the high risk of the development of chronic renal failure and relapse.