血清抗磷脂酶A2受体抗体联合肾小球补体C3沉积与特发性膜性肾病患者临床病理及预后的相关性

Correlation between serum anti-phospholipase A2 receptor antibody combined with glomerular complement C3 deposition and clinicopathology and prognosis in patients with idiopathic membranous nephropathy

目的探讨血清抗磷脂酶A2受体抗体(serum anti-PLA2R antibody,SAb)联合肾小球补体C3(glomerular complement C3,GC3)沉积与特发性膜性肾病(idiopathic membranous nephropathy,IMN)患者临床病理及预后的相关性。方法该研究为回顾性队列研究。纳入2019年7月1日至2022年4月30日于青岛大学附属医院确诊为IMN的患者,收集并分析其临床和病理资料。根据SAb滴度和GC3沉积状态分为SAb阴性和GC3阴性组(SAb^(-)/GC3-组)、SAb阴性和GC3阳性组(SAb^(-)/GC3^(+)组)、SAb阳性和GC3阴性组(SAb^(+)/GC3-组)及SAb阳性和GC3阳性组(SAb^(+)/GC3^(+)组),比较各组患者的临床病理特点。应用Kaplan-Meier生存曲线比较各组患者肾脏缓解率的差异。应用Cox回归模型分析肾脏缓解的相关因素。结果该研究共纳入143例IMN患者,年龄(53.35±12.34)岁,男性94例(65.7%)。其中,SAb^(-)/GC3-组17例(11.9%),SAb^(-)/GC3^(+)组30例(21.0%),SAb^(+)/GC3-组19例(13.3%),SAb^(+)/GC3^(+)组77例(53.8%)。与SAb^(-)/GC3-组相比,SAb^(+)/GC3^(+)组患者血清白蛋白水平较低,24 h尿蛋白量水平、SAb滴度、肾小球抗磷脂酶A2受体抗原阳性比例及肾小管萎缩比例均较高(均P<0.05)。中位随访26.0(19.0,36.0)个月,共96例(67.1%)患者达到缓解。SAb^(+)/GC3^(+)组患者使用免疫抑制治疗比例高于SAb^(-)/GC3-组[93.5%(72/77)比70.6%(12/17),Fisher值=8.974,P=0.016],肾脏缓解比例低于SAb^(-)/GC3-组[49.4%(38/77)比100%(17/17),χ^(2)=25.438,P<0.001]。Kaplan-Meier生存曲线结果显示,SAb^(+)/GC3^(+)组患者的肾脏累积缓解率显著低于SAb^(-)/GC3-组(Log-rankχ^(2)=31.538,P<0.01)。多因素Cox回归分析结果显示,24 h尿蛋白量(HR=0.891,95%CI 0.803~0.988,P=0.029)、SAb滴度(HR=0.996,95%CI 0.992~1.000,P=0.042)、SAb^(+)/GC3^(+)(参照SAb^(-)/GC3-,HR=0.414,95%CI 0.204~0.827,P=0.013)与IMN患者肾脏缓解独立相关。结论SAb阳性且伴有GC3沉积的IMN患者临床及病理改变较重,肾脏累积缓解率较低,更易出现不良预后。联合检测SAb和GC3沉积,可能有助于IMN患者的预后判断和治疗指导。

Objective To investigate the correlation between serum anti-phospholipase A2 receptor antibody(SAb)combined with glomerular complement C3(GC3)deposition and clinicopathologic features and prognosis in patients with idiopathic membranous nephropathy(IMN).Methods It was a retrospective cohort study.The patients diagnosed with IMN in Affiliated Hospital of Qingdao University from July 1,2019 to April 30,2022 were enrolled,and the clinical and pathological data were collected and analyzed.The patients were divided into negative SAb and negative GC3(SAb^(-)/GC3-)group,negative SAb and positive GC3(SAb^(-)/GC3^(+))group,positive SAb and negative GC3(SAb^(+)/GC3-)group and positive SAb and positive GC3(SAb^(+)/GC3^(+))group according to the status of SAb titer and GC3 deposition.Clinical and pathological characteristics among the groups were compared.Kaplan-Meier survival curve was used to compare the cumulative renal remission rates of different groups.Cox regression analysis model was used to analyze the related factors of renal remission.Results A total of 143 IMN patients aged(53.35±12.34)years old were included in the study,including 94 males(65.7%).There were 17 patients(11.9%)in the SAb^(-)/GC3-group,30 patients(21.0%)in the SAb^(-)/GC3^(+)group,19 patients(13.3%)in the SAb^(+)/GC3-group,and 77 patients(53.8%)in the SAb^(+)/GC3^(+)group.Compared with SAb^(-)/GC3-group,the level of serum albumin was lower in the SAb^(+)/GC3^(+)group,and the level of 24 h urine protein,SAb titer,and the proportions of glomerular anti-phospholipase A2 receptor antigen and renal tubule atrophy were higher in the SAb^(+)/GC3^(+)group(all P<0.05).After 26.0(19.0,36.0)months of follow-up,a total of 96 patients(67.1%)attained remission.The proportion of patients receiving immunosuppressive therapy in the SAb^(+)/GC3^(+)group was higher than that in the SAb^(-)/GC3-group[93.5%(72/77)vs.70.6%(12/17),fisher value=8.974,P=0.016]and the proportion of renal remission rate in the SAb^(+)/GC3^(+)group was lower than that in the SAb^(-)/GC3-group[49.4%(38/77)vs.100%(17/17),χ^(2)=25.438,P<0.001].Kaplan-Meier survival curve result showed that the cumulative renal remission rate in the SAb^(+)/GC3^(+)group was significantly lower than that in the SAb^(-)/GC3-group(Log-rankχ^(2)=31.538,P<0.01).Multivariate Cox regression analysis result showed that 24 h urine protein level(HR=0.891,95%CI 0.803-0.988,P=0.029),SAb titer(HR=0.996,95%CI 0.992-1.000,P=0.042)and SAb^(+)/GC3^(+)(with SAb^(-)/GC3-group as reference,HR=0.414,95%CI 0.204-0.827,P=0.013)were independent related factors for renal remission in patients with IMN.Conclusions IMN patients with positive SAb and GC3 deposition have more severe clinical and pathological changes,lower renal cumulative remission rates,and are more likely to have poor prognosis.The combined assessment of SAb and GC3 deposition may be helpful for evaluating prognosis and guiding treatment in IMN patients.