METHODS: Differences in terms of clinical manifestations, disease activity, laboratory parameters, and histology were recorded between patients with focal necrotizing glomerulonephritis (FNGN) due to myeloperoxidase (MPO-), proteinase 3-ANCA(+) [PR3-ANCA(+)], and ANCA(-) disease at time of diagnosis. Patients were treated with the same protocol and followed-up for 24 months, in a scheduled basis of every month for the first year and every 3 months for the second year. Primary end points were: (i) Combined end-stage renal disease (ESRD) and/or death and (ii) The presence of major or minor relapse during follow-up and secondary endpoint was the combination of ESRD and reduction of estimated glomerular filtration rate (eGFR) ≥ 50%.
RESULTS: A total of 92 patients (M/F 39/53, mean age 59.1 ± 15 years) diagnosed with FNGN due to ANCA-associated vasculitis (AAV), 36 (39.1%) patients diagnosed with PR3-ANCA, 39 (42.4%) patients diagnosed with MPO-ANCA, and 17 (18.5%) patients diagnosed with ANCA(-) were included. Number of involved systems differed significantly between PR3-, MPO-ANCA, and ANCA(-), with only renal involvement in 3, 25.5, and 29% of patients, two systems involved in 33, 31, and 59% of patients, and > 3 systems involved in 64, 43.5, and 12% of patients, respectively (p = 0.002). Histology classification revealed focal, crescentic, mixed, and sclerotic type in 14, 64, 19, and 3% of PR3-ANCA(+), 8, 28, 18, and 46% of MPO-ANCA, and 41, 29, 6, and 24% of ANCA(-), respectively (p < 0.0001). Primary end point of ESRD ± Death was reached in 11 (30.6%), 16 (41%), and 6 (35.5%) patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), respectively (p = NS); similarly, ESRD± > 50% eGFR reduction in 8 (22.2%), 15 (38.5%), and 5 (29.4%) patients, respectively (p = NS), meaning that patients with MPO-ANCA(+) showed a propensity to decline renal function. Rate of relapse was increased in the presence of patients with PR3-ANCA(+), 14 (38.9%), 4 (11.8%), and 2 (10.3%) of patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), had at least one relapse during the two-year follow-up (p = 0.006).
CONCLUSIONS: Clinical phenotype and renal histology differ significantly between PR3-ANCA(+), MPO-ANCA(+), and ANCA(-) disease and FNGN; however, renal function outcome is similar, despite the increased rate of relapses in patients with PR3-ANCA(+).
方法:临床表现方面的差异,疾病活动,实验室参数,和组织学记录的患者局灶性坏死性肾小球肾炎(FNGN)由于髓过氧化物酶(MPO-),蛋白酶3-ANCA(+)[PR3-ANCA(+)],和诊断时的ANCA(-)疾病。患者接受相同的治疗方案并随访24个月,在计划的基础上,第一年每个月和第二年每3个月。主要终点是:(i)合并终末期肾病(ESRD)和/或死亡;(ii)随访期间主要或次要复发的存在以及次要终点是ESRD和估计肾小球滤过率降低(eGFR)≥50%。
结果:共有92例患者(M/F39/53,平均年龄59.1±15岁)因ANCA相关血管炎(AAV)而被诊断为FNGN,36例(39.1%)患者诊断为PR3-ANCA,39例(42.4%)患者诊断为MPO-ANCA,纳入17例(18.5%)被诊断为ANCA(-)的患者.涉及的系统数量在PR3-、MPO-ANCA,ANCA(-),3、25.5和29%的患者仅肾脏受累,两个系统涉及33%,31%和59%的患者,>3个系统涉及64、43.5和12%的患者,分别(p=0.002)。组织学分类显示病灶,月牙形,混合,和硬化型在14、64、19和3%的PR3-ANCA(+),8、28、18和46%的MPO-ANCA,和41%、29%、6%和24%的ANCA(-),分别(p<0.0001)。ESRD±死亡的主要终点为11(30.6%),16(41%),6例(35.5%)PR3-ANCA(+)患者,MPO-ANCA(+),ANCA(-),分别(p=NS);类似地,ESRD±>50%eGFR降低8(22.2%),15(38.5%),5名(29.4%)患者,分别(p=NS),意味着MPO-ANCA(+)患者有肾功能下降的倾向。PR3-ANCA(+)患者的复发率增加,14(38.9%),4(11.8%),和2(10.3%)的PR3-ANCA(+)患者,MPO-ANCA(+),ANCA(-),在两年的随访中至少有一次复发(p=0.006)。
结论:PR3-ANCA(+)之间的临床表型和肾脏组织学差异显著,MPO-ANCA(+),和ANCA(-)疾病和FNGN;然而,肾功能结果相似,尽管PR3-ANCA()患者的复发率增加。