抗中性粒细胞胞浆抗体相关血管炎肾损害的临床病理分析

Clinical and pathological characteristics of patient s with ANCA associated vasculitis and renal involvement

目的:分析抗中性粒细胞胞浆抗体(ANCA)相关血管炎(AAV)伴肾损害患者的临床和病理特征。方法:112例临床诊断为AAV,血清ANCA阳性(间接免疫荧光和ELISA法),伴有肾损害并均行肾活检的患者。回顾性分析其临床和病理特征,分析肺出血危险因素及ANCA类型与临床病理的联系。结果:(1)一般情况:男女比例1∶1.6,平均起病年龄(46.3±16.8)岁,半数患者在50岁以后发病,病程0.2～192月(中位病程6个月)。98例(87.5%)MPO-ANCA阳性,13例(11.6%)PR3-ANCA阳性,1例MPO-ANCA与PR3-ANCA双阳性。31%伴血清抗内皮细胞抗体阳性(IIF法),2.7%同时合并抗肾小球基膜抗体(IIF法)。临床类型中微型多血管炎(MPA)102例(占91.1%),韦格纳肉芽肿(WG)10例(占8.9%)。(2)临床表现:首发症状依次为全身症状(30.4%)、肾损害(29.5%)、咯血(13.4%)和皮肤关节损害(16%)。肾外脏器受累率依次为肺(50.9%)、上呼吸道(19.6%)、关节(19.6%)、皮肤(18.8%)、浆膜炎(17.9%)、眼(17.9%)、消化道(8.9%)、心脏(6.3%)和神经系统(5.4%),33%伴有血小板减少。(3)肾损害:92%患者伴肾功能不全[SCr平均(428.7±297.0)μmol/L],37.5%需即时肾脏替代治疗。所有患者有镜下血尿,其中1/4有肉眼血尿,大量蛋白尿比例仅21.4%。肾活检病理:92%患者有肾小球新月体形成[平均新月体比例(63.7±27.9)%],52.7%伴毛细血管袢节段坏死,71.4%伴有球性硬化[平均肾小球硬化比例(41.8±27.8)%],均有小管间质纤维化。(4)伴有肺出血组(n=34)与无肺出血组(n=78)比较,前者肾功能损害更重[SCr(556.0±362.4)vs(373.0±245.8)μmol/L,P<0.01],抗内皮细胞抗体(AECA)阳性率高[48.0%vs24.6%,P<0.05],ANCA水平差异无统计学意义[(307.3±374.1)vs(310.2±444.4),P>0.05]。Logistic回归分析发现AECA阳性为肺出血主要风险因素(P<0.05)。结论:本组AAV以MPO-ANCA相关的MPA为主,发病年龄轻,女性比例高;肾功能损害重且病程迁延,表明早期诊断的必要性;AAV肺出血与血清AECA相关。

Objective：To investigate the clinical and pathological characteristics of ANCA associated vasculitis （AAV） in 112 patients with renal involvement, nethodology：112 patients with renal involvement underwent renal biopsy were diagnosed as AAV with ANCA positive. All clinical and pathological data of these patients were collected and retrospectively analyzed. The risk factors of pulmonary hemorrhage and relationship between ANCA type and clinicopathologic manifestations were noted. Results： （ 1 ） General characteristics： The male and female ratio was 1 ： 1.6, with the average age 46. 3 ± 16. 8 years old. Half of them were diagnosed after 50 years old. The median duratione of disease was 6 months, ranged from 0. 2 to 192 months. The ANCA types were MPO-ANCA （87. 5% ） and PR3-ANCA （ 11.6% ）. Only one patient showed both MPO-ANCA and PR3-ANCA positive. AECA positive was found in 31% of patients. Anti-GBM antibody was positive in three patients. There were 102 patients diagnosed as MPA and 10 as WG. （2）Clinical manifestations： onset symptoms included general symptom （30. 4% ）, renal involvement （29. 5% ）, hemoptysis （ 13.4% ）, and skin and joints involvement （ 16% ）. The extra-renal organ involved lung （50. 9% ）, upper respiratory （ 19.6% ）, joint （ 19.6% ）, skin （ 18.8% ） , serositis （ 17.9% ） , eye （ 17.9% ） , gastrointestinal （ 8.9% ） , heart （ 6. 3% ） and nerve system （ 5.4% ）. Thromboeytopenia was found in 33% of patients. （3） Renal involvement： Renal dysfunction was found in 92% （ average SCr 4. 85 ± 3.36 mg/dl）, initial dialysis was needed in 37. 5% of the patients. Microscopic hematuria was presented in all patients, with gross hematuria in 25% and nephrotie proteinuria in 21.4%. Renal biopsy showed crescent formation （ 92% , average 63.7 ± 27.9% ）, glomerular segmental necrosis （ 52. 7% ）, global sclerosis （ 71.4% , average 41.8 ± 27.8% ） and severe tubular and interstitial fibrosis. （4）Patients with pulmonary hemorrhage （n = 34） had more severe renal failure （ SCr 6. 29 ±4. 10 vs 4. 22 ± 2. 78 ,P 〈0. 01 ） and higher AECA positive （48.0% vs 24. 6% ,P 〈0. 05 ） than those without pulmonary hemorrhage （n=78 ）. AECA was an major risk factor for pulmonary hemorrhage（ Logistic regression analysis, P 〈 0. 05 ）. Conclusion：In this study, MPO-ANCA was the most common ANCA type. The patients were younger and female ratio was higher than those reported by western countries. It is very important for early diagnosis and treatment because higher crescent formation and severe renal dysfunction. AECA positive may be related with pulmonary hemorrhage.