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