儿童激素敏感型肾病综合征的远期结局

Long-term outcomes of childhood steroid-sensitive nephrotic syndrome

目的探讨儿童激素敏感型肾病综合征(SSNS)的远期结局及影响因素。方法回顾性分析2006年1月至2010年12月就诊于中山大学附属第一医院儿科且随访超过10年的105例初治SSNS患者的临床资料,包括一般情况、临床表现、实验室检查、治疗和预后等。主要结局为临床治愈,次要结局为末次随访1年内有复发或未停用激素及免疫抑制剂和末次随访时患者仍存在的并发症。按主要结局分为临床治愈组和未治愈组。采用t检验、Mann-WhitneyU检验、χ2检验等进行组间比较,多因素分析采用二元Logistic回归。结果105例SSNS患者中男82例(78.1%)、女23例(21.9%),起病年龄为3.0(2.1,5.0)岁。随访时间(13.1±1.4)年,频复发或激素依赖者38例(36.2%),无死亡及进展至终末期肾脏病者。临床治愈组88例(83.8%),未治愈组17例(16.2%),末次随访1年内有复发或仍未停药者14例(13.3%)。未治愈组频复发或激素依赖比例[12/17比29.5%(26/88),χ2=10.39]、应用免疫抑制剂比例[13/17比18.2%(16/88),χ2=21.39]和起病时载脂蛋白A1水平[(2.0±0.5)比(1.7±0.6)g/L,t=2.02]均高于治愈组(均P<0.05)。多因素Logistic回归分析发现应用免疫抑制剂者远期仍未达临床治愈的风险增高(OR=14.63,95%CI 4.21~50.78,P<0.001)。在达临床治愈且复发过的55例患者中,48例(87.3%)在12岁之后不再复发。105例SSNS患者的末次随访年龄为16.4(14.6,18.9)岁,≥18岁者34例(32.4%),其中5例(14.7%)在末次随访1年内仍有复发或未停药。105例患者末次随访时仍存在远期并发症者13例,其中8例为频复发或激素依赖。频复发或激素依赖者末次随访时合并矮小症、肥胖症、白内障及骨质疏松引起的骨质事件的发生率分别为10.5%(4/38)、7.9%(3/38)、5.3%(2/38)和2.6%(1/38)。结论SSNS患者大多数达临床治愈,远期预后较好,应用免疫抑制剂是远期未达临床治愈的独立危险因素;但儿童SSNS迁延至成年期并不少见,应加强对频复发或激素依赖者远期并发症的防控。

Objective To investigate the long-term outcomes and risk factors in children with steroid-sensitive nephrotic syndrome(SSNS).MethodsA retrospective cohort study was conducted on newly onset SSNS admitted to the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University from January 2006 to December 2010 and 105 cases with follow-up for more than 10 years were included.Clinical data including general characteristics,clinical manifestation,laboratory tests,treatment and prognosis.The primary outcome was the clinical cure,and the secondary outcomes were relapse or ongoing immunosuppressive treatment within the last 1 year of follow-up and complications at the last follow-up.According to the primary outcome,the patients were divided into clinical cured group and uncured group.Categorical variables were compared between 2 groups using theχ2 or Fisher exact test,and continuous variables by t or Mann-Whitney U test.Multiple Logistic regression models were used for multivariate analysis.ResultsOf the 105 children with SSNS,the age of onset was 3.0(2.1,5.0)years,and 82(78.1%)were boys,23(21.9%)were girls.The follow-up time was(13.1±1.4)years;38 patients(36.2%)had frequently relapsing or steroid-dependent nephrotic syndrome(FRNS or SDNS)and no death or progression to end-stage kidney disease.Eighty-eight patients(83.8%)were clinically cured.Seventeen patients(16.2%)did not reach the clinical cure criteria,and 14 patients(13.3%)had relapsed or ongoing immunosuppressive treatment within the last year of follow-up.The proportion of FRNS or SDNS(12/17 vs.29.5%(26/88),χ2=10.39),the proportion of treatment with second-line immunosuppressive therapy(13/17 vs.18.2%(16/88),χ2=21.39),and the level of apolipoprotein A1 at onset((2.0±0.5)vs.(1.7±0.6)g/L,t=2.02)in the uncured group were higher than those in the clinical cured group(allP<0.05).Multivariate Logistic regression analysis showed that patients treated with immunosuppressive therapy had an increased risk of not reaching clinical cure in the long term(OR=14.63,95%CI 4.21-50.78,P<0.001).Of the 55 clinically cured patients who had relapsed,48 patients(87.3%)did not relapse after 12 years of age.The age at last follow-up was 16.4(14.6,18.9)years,and 34 patients(32.4%)were≥18 years of age.Among the 34 patients who had reached adulthood,5 patients(14.7%)still relapsed or ongoing immunosuppressive treatment within the last year of follow-up.At the last follow-up,among the 105 patients,13 still had long-term complications,and 8 patients were FRNS or SDNS.The proportion of FRNS or SDNS patients with short stature,obesity,cataracts,and osteoporotic bone fracture was 10.5%(4/38),7.9%(3/38),5.3%(2/38),and 2.6%(1/38),respectively.ConclusionsThe majority of SSNS children were clinically cured,indicating a favorable long-term prognosis.History of treatment with second-line immunosuppressive therapy was the independent risk factor for patients not reaching the clinical cure criteria in the long term.While it is not uncommon for children with SSNS to persist into adulthood.The prevention and control of long-term complications of FRNS or SDNS patients should be strengthened.