中国循证儿科杂志 ›› 2024, Vol. 19 ›› Issue (1): 36-42.DOI: 10.3969/j.issn.1673-5501.2024.01.007

• 论著 • 上一篇    下一篇

儿童肾小管间质性肾炎-葡萄膜炎综合征临床和病理特征回顾性队列研究

徐可1,任雅丽2,王芳1,姚勇1,肖慧捷1,钟旭辉1,刘晓宇1,苏白鸽1,张宏文1,王素霞2,丁洁1,管娜1   

  1. 北京大学第一医院 北京,100034;1儿科,2电镜室
  • 收稿日期:2023-11-23 修回日期:2024-02-25 出版日期:2024-02-25 发布日期:2024-02-25
  • 通讯作者: 王芳

Clinical and pathological characteristics of 10 pediatric patients with tubulointerstitial nephritis and uveitis

XU Ke1, REN Yali2, WANG Fang1, YAO Yong1, XIAO Huijie1, ZHONG Xuhui1, LIU Xiaoyu1, SU Baige1, ZHANG Hongwen1, WANG Suxia2, DING Jie1, GUAN Na1   

  1. Peking University First Hospital, Beijing 100034, China; 1 Department of Pediatrics, 2 Laboratory of Electron Microscopy

  • Received:2023-11-23 Revised:2024-02-25 Online:2024-02-25 Published:2024-02-25
  • Contact: WANG Fang

摘要: 背景 国外研究报道肾小管间质性肾炎-葡萄膜炎(TINU)综合征在儿童急性间质性肾炎(AIN)中的占比较高,但部分患儿临床表现不典型,易漏诊,目前我国关于TINU综合征在AIN患儿中的占比及其预后尚不明确。 目的 分析AIN患儿中TINU综合征的临床和病理特征。 设计回顾性队列研究。 方法 纳入2012年1月至2022年12月在北京大学第一医院经肾活检病理证实的AIN患儿,根据末次随访时的最终诊断分为TINU组和非TINU组。截取患儿的发病年龄、性别、既往史、前驱感染史、用药史,起病和复诊时临床表现、眼科会诊结果,首次就诊时的实验室检查结果,肾活检病理资料,治疗和随访情况。 主要结局指标 TINU综合征患儿的肾脏和眼部表现,治疗和预后。 结果 共21例AIN患儿纳入本研究,占同期肾活检患儿的1.6%。TINU组10例(48%),非TINU组11例(干燥综合征2例,药物相关和结节病各1例,病因不详7例)。TINU患儿中5例在肾活检前或同时、5例在肾活检后1~12个月诊断葡萄膜炎,均为双眼受累,前葡萄膜炎4例,全葡萄膜炎6例;非TINU组中的1例结节病患儿在病初诊断为葡萄膜炎。10例TINU患儿中,男、女各5例,起病年龄8~15岁,3例有前驱感染史,4例有药物治疗史,就诊时均有纳差\体重下降,发热4例,关节痛2例,眼部结膜充血、疼痛、流泪2例;有泡沫尿4例,尿量增多/新发夜尿6例,血压升高2例。经过全身和眼部应用糖皮质激素后,10例TINU组患儿肾脏表现均改善或消失,6例葡萄膜炎好转,未好转的1例予糖皮质激素点眼、3例联合其他免疫抑制剂治疗。随访时间为11(4, 21)个月,2例在泼尼松停用或减量时出现AIN症状反复,予糖皮质激素和免疫抑制剂治疗后好转;2例出现眼部并发症(1例双眼继发性青光眼伴双侧视野缺损、1例白内障),3例仍有葡萄膜炎。TINU与非TINU所致的AIN患儿比较,人口学资料、发病年龄、前驱感染史、用药史、首诊时有眼部症状的患儿比例、其他临床症状、实验室检查指标、肾脏病理表现、肾脏复发比例等差异均无统计学意义。 结论 除眼部病变外,TINU综合征与其他病因所致AIN在临床表现、实验室检查和病理改变均类似;葡萄膜炎的临床表现隐匿,可晚于肾脏症状出现,对AIN患儿应重视眼科病史收集、眼科检查和随诊,以免漏诊TINU综合征。

关键词: 急性间质性肾炎, 葡萄膜炎, 儿童, 病理

Abstract: Background Foreign studies have reported that tubulointerstitial nephritis-uveitis (TINU) syndrome accounts for a relatively high proportion of acute interstitial nephritis (AIN) in children, but some children have atypical clinical manifestations and are likely to be misdiagnosed. At present, the proportion and prognosis of TINU syndrome in children with AIN are not clear in China. Objective To analyze the clinical and pathological characteristics of TINU syndrome in AIN children. Design Retrospective cohort study. Methods The clinical and pathological manifestations in AIN children confirmed by renal biopsy in our hospital from January 2012 to December 2022 were retrospectively collected and analyzed. According to the final diagnosis at the last follow-up, the patients were divided into the TINU syndrome group and the non-TINU syndrome group. The age of onset, sex, past history, history of prodromal infection, medication history, clinical manifestations at onset and return visit, ophthalmic consultation results, laboratory examination results at the first visit, pathological data of kidney biopsy, and treatment and follow-up were intercepted. Main outcome measures Kidney and ocular manifestations as well as the associated treatment and prognosis in children with TINU. Results Twenty-one AIN children were included in this study, accounting for 16% of AIN children confirmed by renal biopsy. There were ten cases (48%) in the TINU syndrome group and 11 cases in the non-TINU syndrome group including 2 for Sjogren syndrome, 1 for drug induction, 1 for sarcoidosis, and 7 for unclear reasons. Among the TINU children, uveitis was diagnosed before or simultaneously with renal biopsy in 5 cases , and 1 to 12 months after renal biopsy in the other 5 cases with binocular involvement. There were 4 cases of anterior uveitis and 6 cases of panuveitis. One child with sarcoidosis in the non-TINU group was diagnosed with uveitis at the beginning. Among the 10 children with TINU, 5 cases were males and the others were female with the onset age of 8 to 15 years old, among which 3 had a history of precursor infection, 4 had a history of medication treatment with weight loss or poor appetite at admission, 4 had fever, 2 had joint pain, 2 had conjunctival congestion, pain and tears, 4 had foam urine, 6 had increased urine volume or new nocturia, and 2 had increased blood pressure. After systemic and ocular application of corticosteroids, the renal manifestations of 10 TINU cases improved or disappeared, and 6 cases of uveitis improved. As the symptoms of uveitis did not improve, one case received corticosteroid eye drops and three cases combined with other immunosuppressive therapy. At a follow-up of 11 (4,21) months, two had repeated AIN symptoms of after prednisone withdrawal or reduction, and improved after reveiving glucocorticoids and immunosuppressive agents again; two had ocular complications (one for secondary glaucoma in both eyes with bilateral visual field defects, the other one for cataract), and three still had uveitis. Compared with children with AIN caused by TINU and non-TINU, there were no statistically significant differences in demographic data, age of onset, history of prodromal infection, medication history, the proportion of children with ocular symptoms at first diagnosis, other clinical symptoms, laboratory indicators, renal pathological manifestations, and the proportion of renal recurrence. Conclusion Besides specific ocular lesions, AIN by TINU syndrome exhibits similar clinical manifestations, laboratory findings, and pathological changes to AIN by non-TINU syndrome. The clinical symptoms of uveitis are often subtle and may appear several months after renal symptoms. Ophthalmic history data of all pediatric AIN patients should be collected, and these patients should undergo systematic ophthalmic examination and receive regular follow-up visits from ophthalmologists.

Key words: Acute interstitial nephritis, Uveitis, Child, Pathology