A Comprehensive Review of Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome

Abstract

Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disorder, characterized by acute tubulointerstitial nephritis and uveitis. It poses diagnostic challenges due to the mostly asynchronous onset of renal and ocular manifestations, as well as the variety of differential diagnoses. This review provides an overview of the epidemiology, pathogenesis, clinical features, diagnostic criteria, and management strategies. Methods: A comprehensive review of the peer-reviewed literature, including studies and case reports, was conducted. Results: The etiology of TINU syndrome involves an autoimmune reaction to renal and ocular antigens, leading to interstitial inflammation and tubular damage in the kidneys, and anterior uveitis with acute onset of flares. Diagnostic criteria based on ocular examination, laboratory parameters, and renal biopsy emphasize the need to exclude other systemic diseases. TINU syndrome accounts for approximately 2% of all uveitis cases. Primary treatment consists of corticosteroids, while immunomodulatory therapies (methotrexate, azathioprine, mycophenolate mofetil, or biologic agents) are reserved for refractory cases. Recurrence of uveitis appears to be more common than that of nephritis. Conclusions: TINU syndrome is rare and requires clinical suspicion for accurate diagnosis. Early diagnosis and initiation of treatment are crucial for achieving favorable outcomes. Advances in the understanding of its pathogenesis and treatment have improved patient outcomes. Further research is needed to investigate the underlying triggers and mechanisms in order to develop targeted therapies.

Keywords: TINU syndrome; autoimmune diseases; biologic agents; corticosteroids; diagnosis; immunomodulatory therapies; pathophysiology; treatment; tubulointerstitial nephritis; uveitis.

Figure 1

Pathophysiology of TINU syndrome. Drug-related toxicity or infections may trigger an immunological cascade, potentially activating B-cells and leading to the production of antibodies against modified C-reactive protein (anti-mCRP). These antibodies target mCRP proteins in the uvea, renal interstitium, or tubules, resulting in uveitis and acute interstitial nephritis. (Created in BioRender. Bograd, A. (2025) https://BioRender.com/z95m909, accessed on 22 January 2025).

Figure 2

Diagnostic criteria for tubulointerstitial nephritis and uveitis syndrome, based on the publications of Mandeville et al. [4] and Bograd et al. [37].

Figure 3

Definition of typical and atypical uveitis in TINU syndrome based on clinical presentation and timepoint of onset in relation to acute interstitial nephritis (AIN), according to Mandeville et al. [4] and Bograd et al. [37].

Figure 4

Treatment algorithm for TINU syndrome. Initial management of anterior uveitis involves the use of topical corticosteroids (e.g., initially administered hourly, followed six times daily, with a gradual reduction by one drop per week). Following confirmation of TINU syndrome and exclusion of underlying infectious diseases, systemic corticosteroids (e.g., 1 mg/kg body weight/day) should be initiated. If both renal and ocular inflammation are effectively controlled, the therapy can be tapered gradually. In cases of recurrence or insufficient response to systemic corticosteroids, escalation to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) is recommended. If necessary, biologic DMARDs (bDMARDs), particularly TNF-alpha inhibitors, may be considered.