[Treatment effectiveness and long-term prognosis of childhood-onset lupus nephritis].

Objectives: To analyze the clinical characteristics, treatment effectiveness and long-term prognosis of childhood-onset lupus nephritis (LN), and to explore the risk factors for progression to end-stage renal disease (ESRD). Methods: In this retrospective study, the clinical data including general conditions, clinical manifestations, laboratory examinations, treatment, following up (till December 31st, 2020) and prognosis of 343 children with LN who were treated and followed up in the First Affiliated Hospital of Sun Yat-sen University from January 1, 2003 to December 31, 2019 were analyzed. Complete remission rates were compared between different pathological types according to renal biopsies and flare rates were compared between complete remission group and partial remission group according to the treatment effectiveness after 6 months of induction treatment. To investigate the risk factors of ESRD, the prognosis of flare and non-flare cases, and of cases with normal and elevated serum creatinine levels at baseline, was compared. Chi-squared tests were used for comparison between groups, and cumulative survival rate and renal survival rates were calculated by Kaplan-Meier survival analysis. Risk factors for ESRD were analyzed by COX regression model. Results: Among the 343 children, 68 were males (19.8%) and 275 were females (80.2%) with a median age of 13.0 (11.0, 16.0) years. Regarding the renal symptoms, 305 (88.9%) children had proteinuria and 245 (71.4%) had hematuria; while for extra-renal manifestations, 273 (79.6%) had anemia, 183 (53.4%) had rashes and 165 (48.1%) had fever. A total of 212 (61.8%) children had severely active SLE at initial presentation. After 6 months of induction treatment, the complete remission rate was 63.8% (219/343) and the partial remission rate was 27.1% (93/343). The complete remission rate was significantly higher in type Ⅰ and type Ⅱ LN compared to type Ⅳ LN (10/12 vs. 82/135 (60.7%), χ²=3.936, P=0.047). One hundred and ten children who achieved remission, including complete remission and partial remission, experienced renal flare with a flare rate of 35.3% and a mean time to flare was (43.2±28.4) months. There was no significant difference in flare rates between complete and partial remission group (36.1% (79/219) vs. 33.3% (31/93), χ²=3.394, P=0.065). The follow-up time of all the children was 60.4 (32.3, 100.9) months. During the follow-up period, 15 children died and the cumulative survival rates at 3, 5 and 10 years were 97.2%, 96.4% and 93.3%, respectively; 14 children progressed to ESRD and the cumulative renal survival rates at 3, 5, and 10 years were 99.2%, 97.1%, and 93.4%, respectively. COX multivariate analysis demonstrated that elevated serum creatinine at baseline, nephritic flare and nephrotic flare were independent risk factors for progression of ESRD (hazard ratio (HR)=3.575, 21.550 and 8.590, 95%CI 1.127-11.341, 2.394-194.027 and 1.042-70.823, P=0.031, 0.006, and 0.046, respectively). Conclusions: Children with LN are characterized by high SLE disease activity and multi-system involvement at onset. After 6 months of induction treatment, most of LN children could achieve clinical remission but some would experience renal flare. Nephritic flare, nephrotic flare and elevated serum creatinine at onset are independent risk factors for the progression of ESRD in children with LN.目的： 总结儿童狼疮性肾炎（LN）的临床特征并分析其治疗效果及远期预后，探讨LN患儿进展至终末期肾脏病（ESRD）的危险因素。 方法： 回顾性分析2003年1月至2019年12月于中山大学附属第一医院治疗并随访的343例LN患儿的一般情况、临床表现、实验室检查、治疗、随访（截至12月31日）和预后情况等临床资料。根据肾活检病理的不同分型比较其完全缓解率；根据诱导治疗6个月后缓解情况分为完全缓解组和部分缓解组比较其复发情况；按复发情况分为无复发组、蛋白尿型复发组和肾炎型复发组；按起病时血肌酐有无升高分为血肌酐正常组和血肌酐升高组。组间比较采用χ²检验，采用Kaplan-Meier生存分析计算患儿存活率及肾脏存活率，ESRD的危险因素采用COX比例风险回归模型进行分析。 结果： 343例LN患儿中男68例（19.8%）、女275例（80.2%），发病年龄为13.0（11.0，16.0）岁。LN患儿的肾脏表现中蛋白尿305例（88.9%）、血尿245例（71.4%）；肾外表现中贫血273例（79.6%）、皮疹183例（53.4%）和发热165例（48.1%）。212例（61.8%）患儿起病时为重度狼疮活动。LN患儿诱导治疗6个月后完全缓解率为63.8%（219/343），部分缓解率为27.1%（93/343）；Ⅰ和Ⅱ型患儿的完全缓解率高于Ⅳ型［10/12比60.7%（82/135），χ²=3.936，P=0.047］。共110例（35.3%）诱导缓解（完全缓解和部分缓解）的患儿出现复发，复发时间为（43.2±28.4）个月，79例为完全缓解后复发，31例为部分缓解后复发，完全缓解和部分缓解患儿的复发率差异无统计学意义［36.1%（79/219）比33.3%（31/93），χ²=3.394，P=0.065］。343例患儿随访时间为60.4（32.3，100.9）个月。随访期间共15例患儿死亡，LN患儿3、5、10年的累积存活率分别为97.2%、96.4%、93.3%；共14例患儿进展至ESRD，LN患儿的3、5、10年累积肾脏存活率分别为99.2%、97.1%、93.4%。COX多因素分析显示起病时血肌酐升高、肾炎型复发和蛋白尿型复发为进展至ESRD的独立危险因素（风险比=3.575、21.550、8.590，95%CI：1.127~11.341、2.394~194.027、1.042~70.823，P=0.031、0.006、0.046）。 结论： 儿童LN起病时SLE疾病活动度高，常为多系统受累，经6个月诱导治疗大多数LN患儿可达到临床缓解，但部分患儿诱导缓解后复发；肾炎型复发和蛋白尿型复发、起病时血肌酐升高为LN患儿进展至ESRD的独立危险因素。.