Tubulointerstitial nephritis and uveitis: A multidisciplinary approach to diagnosing a rare disease

(Image Credit: AdobeStock/Елена Бутусова)

German researchers described a rare case of tubulointerstitial nephritis and uveitis (TINU) syndrome in a teenager,¹ the management of which requires a multidisciplinary approach.

TINU is a rare autoimmune disorder that affects the kidneys and eyes concurrently; in the eyes, the most common presentation is bilateral, non-granulomatous anterior uveitis.^2-4 TINU predominantly affects adolescents and young adults, with a median time of onset around 14 to 15 years of age^5,6 and patients are predominantly female,^6,7 according to Markus Kerner, MD, a general practitioner in Neuffen, Germany, and colleagues.

The clinical presentation is heterogeneous and often nonspecific.^3,8 Renal manifestations may include fatigue, flank discomfort, polyuria, or signs of acute kidney injury^3,9; ocular symptoms are bilateral anterior uveitis with pain, photophobia, or visual disturbances.^3,8 However, some patients can be asymptomatic, and uveitis may be discovered incidentally on ophthalmologic examination,¹⁰ they explained.

Renal and ocular symptoms can occur simultaneously or sequentially, which may delay diagnosis.^8,11 Uveitis frequently persists or can relapse.³

TINU case report

They described the case of a 15-year-old girl who presented to her general practitioner with the complaints of fatigue and polyuria. She also reported a recent intentional weight loss. The onset of TINU occurred after she started treatment with sertraline for depression, suggesting a possible drug trigger.

Evaluation revealed acute kidney injury with elevated serum creatinine and a tubular pattern of proteinuria, mild anemia, elevated ferritin levels, and abnormal urinalysis with proteinuria, glucosuria, hematuria, and microalbuminuria; the patient was admitted to a pediatric hospital. A renal biopsy confirmed acute, non-granulomatous tubulointerstitial nephritis. An ophthalmologic examination revealed bilateral anterior uveitis, which confirmed the diagnosis of TINU syndrome.

Regarding ocular involvement, Kerner and colleagues noted that while the patient had no ocular complaints at presentation, the ocular involvement was not clinically apparent. This agreed with previous reports that the uveitis can be mild, bilateral, and asymptomatic, underscoring the importance of proactive ophthalmologic assessment in patients with unexplained interstitial nephritis.^2,12 “The temporally dissociated onset of renal and ocular findings remains one of the principal challenges in TINU diagnosis,^8,13” they commented.

Treatment included high-dose oral steroids that resulted in recovery of renal function and general well-being. The patient was followed by pediatric nephrology and ophthalmology.

Kerner and colleagues also pointed out, “Long-term outcomes in TINU syndrome are generally favorable when the condition is identified early and managed appropriately. Nevertheless, uveitis tends to relapse more frequently than nephritis and may persist or reappear months to years after the initial episode.^14-16 Regular follow-up with both pediatric nephrology and ophthalmology remains essential.”

They concluded, “This case illustrates how clinical vigilance in primary care can facilitate the early recognition of TINU syndrome in an adolescent presenting with nonspecific systemic and renal symptoms.”

References

1. Kerner M, Todoroff J, Von Schnakenburg C, Amann K, Müller-Kühnle J. Fatigue, polyuria, and hidden uveitis: a case of tubulointerstitial nephritis and uveitis syndrome diagnosed in primary care. Cureus. 12025;7: e89245. doi:10.7759/cureus.89245

2. Bograd A, Heiligenhaus A, Reuter S, Tappeiner C. A comprehensive review of tubulointerstitial nephritis and uveitis (TINU) syndrome. Biomedicines. 2025;13:10.3390/biomedicines13020300

3. Clive DM, Vanguri VK. The syndrome of tubulointerstitial nephritis with uveitis (TINU). Am J Kidney Dis. 2018;72:118-28.10.1053/j.ajkd.2017.11.013

4. Sanchez-Quiros J, Giralt L, Fonollosa A, Robles I, Carreño E. Diagnostic and management strategies of tubulointerstitial nephritis and uveitis syndrome (TINU): current perspectives. Clin Ophthalmol. 2023;17:2625-30. 10.2147/OPTH.S404644

5. Matsumoto K, Fukunari K, Ikeda Y, et al. A report of an adult case of tubulointerstitial nephritis and uveitis (TINU) syndrome, with a review of 102 Japanese cases. Am J Case Rep. 2015;16:119-23. 10.12659/AJCR.892788

6. Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol. 2001;46:195-208. 10.1016/s0039-6257(01)00261-2

7. Aguilar MC, Lonngi M, de-la-Torre A. Tubulointerstitial nephritis and uveitis syndrome: case report and review of the literature. Ocul Immunol Inflamm. 2016;24:415-21. 10.3109/09273948.2015.1034374

8. Takemura T, Okada M, Hino S, et al.: Course and outcome of tubulointerstitial nephritis and uveitis syndrome. Am J Kidney Dis. 1999, 34:1016-21. 10.1016/S0272-6386(99)70006-5

9. Mackensen F, Billing H. Tubulointerstitial nephritis and uveitis syndrome. Curr Opin Ophthalmol. 2009;20:525-31. 10.1097/ICU.0b013e3283318f9a

10. Classification criteria for tubulointerstitial nephritis with uveitis syndrome. Am J Ophthalmol. 2021;228:255-61. 10.1016/j.ajo.2021.03.041

11. Ferrario F, Vanzati A, Pagni F. Pathology of ANCA-associated vasculitis. Clin Exp Nephrol. 2013, 17:652-8. 10.1007/s10157-012-0701-8

12. Amaro D, Carreño E, Steeples LR, Oliveira-Ramos F, Marques-Neves C, Leal I. Tubulointerstitial nephritis and uveitis (TINU) syndrome: a review. Br J Ophthalmol. 2020, 104:742-7. 10.1136/bjophthalmol-2019-314926

13. Paroli MP, Cappiello D, Staccini D, Caccavale R, Paroli M. Tubulointerstitial nephritis and uveitis syndrome (TINU): a case series in a tertiary care uveitis setting. J Clin Med. 2022;11:10.3390/jcm11174995

14. Koreishi AF, Zhou M, Goldstein DA. Tubulointerstitial nephritis and uveitis syndrome: characterization of clinical features. Ocul Immunol Inflamm. 2021;29:1312-7. 10.1080/09273948.2020.1736311

15. Sobolewska B, Bayyoud T, Deuter C, Doycheva D, Zierhut M. Long-term follow-up of patients with tubulointerstitial nephritis and uveitis (TINU) syndrome. Ocul Immunol Inflamm. 2018;26:601-7.10.1080/09273948.2016.1247872

16. Khochtali S, Harzallah O, Hadhri R, Hamdi C, Zaouali S, Khairallah M. Neuroretinitis: a rare feature of tubulointerstitial nephritis and uveitis syndrome. Int Ophthalmol. 2014, 34:629-33. 10.1007/s10792-013-9820-9