130例儿童紫癜性肾炎临床病理5年随访研究

A five-year follow-up study on the clinicopathology of 130 children with Henoch-Schönlein purpura nephritis

目的分析儿童紫癜性肾炎(Henoch-Sch?nlein purpura nephritis, HSPN)的临床病理改变特点及其预后。方法回顾性分析2001年1月至2015年6月在南京大学医学院附属金陵医院接受过肾活检且随访时间≥5年的HSPN患儿临床病理资料。随访终点事件定义为估算肾小球滤过率(eGFR)<90 ml·min-1·(1.73 m2)-1。按照患儿是否发生终点事件将入选者分为达终点事件组和未达终点事件组。采用Cox比例风险模型法分析HSPN患儿肾脏不良预后的影响因素。用Kaplan-Meier生存曲线法进行生存分析, Log-rank检验比较肾小球节段性硬化(S1)组和无肾小球节段性硬化(S0)组患儿肾脏累积生存率的差异;采用受试者工作特征曲线(ROC)及曲线下面积(AUC)评价诊断价值。结果共130例HSPN患儿纳入本研究, 中位发病年龄为11.7(8.6, 13.3)岁, 男性71例(54.6%), 中位随访时间为100.0(75.8, 119.0)个月, 有12例(9.23%)患儿发生终点事件。与未达终点事件组(n=118)比较, 达终点事件组(n=12)患儿基线高血压比例、24 h尿蛋白量、血总胆固醇、血尿酸、血肌酐水平较高, 血白蛋白水平较低(均P<0.05)。两组患儿用药种类的差异无统计学意义(均P>0.05)。在肾组织病理改变方面, 与未达终点事件组比较, 达终点事件组患儿系膜细胞增生(M1)、S1、肾小管萎缩或间质纤维化(T1/T2)和球囊粘连的比例较高(均P<0.05)。多因素Cox回归分析结果显示, S1是肾脏不良预后的独立危险因素(HR=7.739, 95%CI 1.422~42.114, P=0.018)。生存分析结果显示, S1组患儿肾脏累积生存率明显低于S0组(Log-rankχ2=17.069, P<0.001)。ROC曲线评估S1预测肾脏不良预后发生的AUC为0.710(95%CI 0.549~0.872), 敏感度为0.667(95%CI 0.349~0.901), 特异度为0.754(95%CI 0.666~0.829)。结论 S1是HSPN患儿肾脏不良预后的独立危险因素, 具有预测诊断价值。

Objective To analyze the clinicopathologic features and prognosis of children with Henoch-Schönlein purpura nephritis(HSPN).Methods The clinicopathological data of children with HSPN who were followed up for more than 5 years and underwent renal biopsy in Jinling Hospital affiliated to Medical School of Nanjing University from January 2001 to June 2015 were retrospectively analyzed.The follow-up endpoint event was defined as estimated glomerular filtration rate(eGFR)<90 ml·min-1·(1.73 m2)-1.Participants were divided into two groups according to whether the children had reached the primary endpoint event or not.Cox proportional hazards model was used to analyze the influencing factors of renal poor prognosis in children with HSPN.Kaplan-Meier survival curve method was used for survival analysis,and log-rank test was used to compare the difference of renal cumulative survival rate between segmental sclerosis/adhesion(S1)group and non-segmental sclerosis/adhesion(S0)group.Receiver operating characteristic curve(ROC curve)and area under the curve(AUC)were used to evaluate the diagnostic value.Results A total of 130 children with HSPN were enrolled in the study.The median onset age was 11.7(8.6,13.3)years old,of whom 71 cases were males(54.6%).At a median follow-up time of 100.0(75.8,119.0)months,12 cases(9.23%)with HSPN reached the primary endpoint event.Compared with the non-endpoint event group,the endpoint event group had higher proportion of hypertension,higher levels of 24-hour urinary protein,serum cholesterol,serum uric acid,and serum creatinine,and lower levels of serum albumin(all P<0.05).There was no statistical difference in treatment between the two groups(all P>0.05).In terms of pathological features,compared with the non-endpoint event group,the endpoint event group had higher proportion of mesangial hyperplasia(M1),S1,tubular atrophy/interstitial fibrosis(T1/T2)and Glomerulus-Bowman's capsule adhesion(all P<0.05).Multivariate Cox regression model showed that S1 was significantly correlated with renal poor prognosis(HR=7.739,95%CI 1.422-42.114,P=0.018).As was revealed in a Kaplan-Meier plot,renal cumulative survival rate in the S1 group was significantly lower than that in the S0 group(log-rankχ2=17.069,P<0.001).The ROC curve showed S1 accurately predicted the outcome(AUC=0.710,95%CI 0.549-0.872)with specificity of 0.667(95%CI 0.349-0.901)and specificity of 0.754(95%CI 0.667-0.829).Conclusions S1 is an independent risk factor affecting renal poor prognosis and has a diagnostic value.