51例儿童急性间质性肾炎临床与病理分析

Clinical and renal pathologic analysis of acute interstitial nephritis in 51 children

目的探讨儿童急性间质性肾炎(acute interstitial nephritis,AIN)的病因、临床表现和肾脏病理特点及其危险因素。方法回顾性收集解放军东部战区总医院2010年1月至2019年12月经肾穿刺活检术确诊为AIN儿童的病因、临床表现、实验室检查结果、治疗方法和预后等资料。采用Kaplan-Meier法评估AIN儿童的肾脏存活率。采用Cox回归模型分析AIN患儿基线时进展为终末期肾病(end-stage renal disease,ESRD)的风险因素。结果共纳入AIN患儿51例,男36例,女15例,年龄(12.94±2.55)岁(2~17岁)。儿童AIN临床表现多样,缺乏特异性,三联征只有2例(3.92%)。51例AIN患儿均表现为急性肾损伤(acute kidney injury,AKI),伴不同程度的血清肌酐升高和估算肾小球滤过率降低,AKI分期以Ⅲ期为主[33例(64.71%)]。感染是儿童AIN的主要病因[38例(74.51%)],其次是药物因素[27例(52.94%)],药物导致的AIN以非甾体抗炎药为主[18例(35.29%)]。51例患儿均有间质炎性细胞浸润或间质水肿。间质炎性细胞浸润以单个核细胞为主[46例(90.20%)]。治疗4周后肾功能完全恢复、部分恢复和无恢复的例数分别为32例(62.75%)、11例(21.57%)和8例(15.69%);治疗12周后,肾功能完全恢复、部分恢复和无恢复的例数分别为49例(96.08%)、0例(0)和2例(3.92%)。经过平均4.0(2.0~15.0)个月的随访,有2例(3.92%)患儿进展至ESRD。肾活检后1年和2年的累积肾脏生存率都为100%,5年和10年的肾脏生存率分别为96.55%和72.41%。多因素Cox回归分析结果表明,尿N-乙酰-β-D-葡萄糖苷酶>17.6 U/g·cr(HR=15.729,95%CI 1.045~15.977,P=0.042)和肾组织IgM沉积(HR=7.523,95%CI 1.142~9.541,P=0.033)是AIN儿童进展至ESRD的独立危险因素。结论AIN儿童临床均表现为AKI,以Ⅲ期为主,肾脏病理特征为小管间质病变。经积极治疗后,大部分AIN患儿预后良好。预防感染及合理用药是降低儿童AIN发病率的关键。尿N-乙酰-β-D-葡萄糖苷酶>17.6 U/g·cr和肾组织IgM沉积是AIN儿童进展至ESRD的独立危险因素。

Objective To discuss the etiology,clinical manifestations and renal pathological features of acute interstitial nephritis(AIN)in children.Methods The etiology,clinical manifestations,pathological characteristics,clinical effects and outcome of the children with AIN diagnosed by renal biopsy from January 2010 to December 2019 in Nanjing Jinling Hospital were analyzed retrospectively.The Kaplan-Meier method was used to evaluate the kidney survival rate.Cox regression model was built to analyze the risk factors for developing end-stage renal disease(ESRD)at baseline in AIN children.Results A total of 51 children with AIN were diagnosed by renal biopsy,including 36 males and 15 females.The age was(12.94±2.55)years old(2-17 years old).The clinical manifestations of AIN in children were various and lack of specificity.Only 2 cases(3.92%)had triad.All of the 51 children with AIN showed acute renal injury(AKI),accompanied by increased serum creatinine and decreased estimated glomerular filtration rate.The stage of AKI was mainly stageⅢ(33 cases,64.71%).Infection was the main cause(38 cases,74.51%)and drug factor was the second cause(27 cases,52.94%)in children with AIN.Nonsteroidal antiinflammatory drugs(NSAIDs)were the main inducers of drug-induced AIN(18 cases,35.29%).The interstitial inflammatory cell infiltration or interstitial edema was found in 51 children.The infiltration of inflammatory cells was mainly mononuclear cells(46 cases,90.20%).After 4 weeks of treatment,32 cases(62.75%),11 cases(21.57%)and 8 cases(15.69%)showed complete,partial and no recovery of renal function,respectively.After 12 weeks of treatment,49 cases(96.08%),0 cases(0)and 2 cases(3.92%)showed complete,partial and no recovery of renal function,respectively.After an average follow-up of 4.0(2.0-15.0)months,2 case(3.92%)patients developed ESRD.The cumulative survival rates of ESRD at 1 year and 2 years after renal biopsy both were 100%,and renal survival rates at 5 years and 10 years were 96.55%and 72.41%,respectively.Multivariate Cox regression analysis results showed that N-acetyl-β-D-glucosidase(NAG)enzyme level>17.6 U/g·cr(HR=15.729,95%CI 1.045-15.977,P=0.042)and IgM deposition in renal tissue(HR=7.523,95%CI 1.142-9.541,P=0.033)were independent risk factors for developing ESRD in AIN children.Conclusions AKI is the main clinical manifestation of AIN in children.The characteritic of renal pathology in AIN is tubulointerstitial lesions.After active treatment,most of the patients have a good prognosis.Prevention of infection and rational use of drugs are the key to reduce the incidence rate of AIN in children.The N-acetyl-β-D-glucosidase enzyme level>17.6 U/g·cr and IgM deposition in renal tissue are independent risk factors for developing ESRD in AIN children.