M型磷脂酶A2受体阳性的儿童原发性膜性肾病临床特点和预后分析

Clinical features and prognostic analysis of primary membranous nephropathy in children with positive glomerular M-type phospholipase A2 receptor

目的分析M型磷脂酶A2受体(PLA2R)阳性的原发性膜性肾病(PMN)患儿的临床和预后。方法回顾性分析2006年1月至2018年12月东部战区总医院儿科经肾活检确诊为PMN的69例患儿资料,包括男40例,女29例;平均年龄为14.86岁。根据肾脏病理免疫荧光PLA2R是否阳性,分为PLA2R阳性组和PLA2R阴性组,采用t检验、Mann-Whitney U检验和χ2检验比较2组患儿的临床病理特征,采用Kaplan-Meier法比较2组患儿的远期肾脏生存率和累积缓解率。结果共纳入69例PMN患儿,血清抗PLA2R抗体和肾组织PLA2R的阳性率分别为53.6%(37例)和82.6%(57例)。PLA2R阳性组临床表现为大量蛋白尿的患儿比例较PLA2R阴性组高[55例(96.5%)比9例(75.0%)],血尿素氮水平高于PLA2R阴性组[1.14(0.93,1.54)mg/L比0.80(0.44,1.18)mg/L],估计肾小球滤过率(eGFR)[162.26(139.81,185.53)mL/(min·1.73 m^(2))比199.52(157.58,212.01)mL/(min·1.73 m^(2))]和血IgG[3.58(2.50,5.43)g/L比5.14(4.35,6.03)g/L]低于PLA2R阴性组,差异均有统计学意义(P=0.034、0.049、0.034、0.016)。PLA2R阴性组患儿的累积缓解率较PLA2R阳性组高(P<0.001)。24 h尿蛋白≥50 mg/kg(HR=0.119,95%CI:0.021~0.595,P=0.010)是肾脏预后的独立风险因素,PLA2R(HR=0.263,95%CI:0.125~0.551,P<0.001)和24 h尿蛋白≥50 mg/kg(HR=0.568,95%CI:0.125~0.551,P=0.041)是尿蛋白缓解的独立预测因素,PLA2R(HR=1.020,95%CI:0.698~1.682,P=0.656)与肾脏预后无关。结论PLA2R阳性的PMN患儿病情严重程度高于PLA2R阴性者。PLA2R阴性的PMN患儿的远期累积缓解率高于PLA2R阳性者。

Objective To analyze the clinical and prognosis of primary membranous nephropathy(PMN)in children with positive glomerular M-type phospholipase A2 receptor(PLA2R).Methods A total of 69 children diagnosed with PMN by renal biopsy admitted to the Department of Pediatrics of Eastern Theater Command General Hospital from January 2006 to December 2018 were retrospectively analyzed,including 40 males and 29 females,with an average age of 14.86 years.According to the immunofluorescence of renal pathology,they were divided into PLA2R positive group and PLA2R negative group.Pathological features between 2 groups were compared by the t test,Mann-Whitney U test and Chi-square test.Kaplan-Meier method was used to compare the long-term renal survival rate and cumulative remission rate between 2 groups.Results A total of 69 pediatric PMN patients were included.The po-sitive rates of serum anti-PLA2R antibody and positive expression of PLA2R in renal tissues were 53.6%(37 cases)and 82.6%(57 cases),respectively.The proportion of children with clinical manifestations of large proteinuria[55 cases(96.5%)vs.9 cases(75.0%),P=0.034]was significantly higher in the PLA2R positive group than that of the PLA2R negative group.Blood urea nitrogen level was significantly higher in the PLA2R positive group than that of PLA2R negative group[1.14(0.93,1.54)mg/L vs.0.80(0.44,1.18)mg/L,P=0.049],while estimate glomerular filtration rate(eGFR)[162.26(139.81,185.53)mL/(min·1.73 m^(2))vs.199.52(157.58,212.01)mL/(min·1.73 m^(2)),P=0.034]and serum IgG[3.58(2.50,5.43)g/L vs.5.14(4.35,6.03)g/L,P=0.016]were significantly lower.The cumulative remission rate was significantly higher in the PLA2R negative group than that of PLA2R positive group(P<0.001).The 24 h urinary protein≥50 mg/kg(HR=0.119,95%CI:0.021-0.595,P=0.010)was an independent risk factor for renal prognosis,and PLA2R(HR=0.263,95%CI:0.125-0.551,P<0.001)and 24 h urinary protein≥50 mg/kg(HR=0.568,95%CI:0.125-0.551,P=0.041)were independent predictors of urinary protein remission.PLA2R(HR=1.020,95%CI:0.698-1.682,P=0.656)was not associated with renal prognosis.Conclusions The severity of PMN in children with positive PLA2R was higher than that in those with negative PLA2R.The long-term cumulative remission rate of PLA2R negative children with PMN was higher than that of PLA2R positive children.