What is the treatment for Tubulointerstitial Nephritis and Uveitis (TINU)?

Treatment of TINU Syndrome

Corticosteroids are the primary treatment for TINU syndrome, with systemic corticosteroids addressing both the tubulointerstitial nephritis and uveitis components, though immunosuppressive agents (methotrexate, azathioprine, mycophenolate mofetil) or biologic therapy (adalimumab, infliximab) should be initiated for corticosteroid-refractory or frequently relapsing disease. 1, 2, 3

Initial Management Approach

Nephritis Component

• Systemic corticosteroids are the cornerstone of treatment for acute tubulointerstitial nephritis in TINU syndrome, with most patients showing recovery of renal function (complete in some cases, partial in others). 4
• Oral prednisone at 0.5-1 mg/kg/day is the typical starting dose, though specific dosing protocols for TINU are not standardized due to the rarity of the condition. 1, 5
• Renal function typically recovers within 6 weeks of corticosteroid initiation, though monitoring should continue as some patients may require hemodialysis in severe cases. 4, 6

Uveitis Component

• Topical corticosteroids (prednisolone acetate or dexamethasone) should be initiated immediately for the bilateral non-granulomatous anterior uveitis characteristic of TINU. 4, 7
• Urgent ophthalmology evaluation within 1-2 days is mandatory to assess severity, evaluate for complications, and guide local treatment intensity. 8, 7
• Approximately 22% of patients respond adequately to topical corticosteroids alone, while others require systemic therapy. 3

Escalation to Immunosuppressive Therapy

Immunosuppressive agents should be introduced when:

• Uveitis remains active despite 3 months of corticosteroid therapy 7
• Disease reactivates during corticosteroid dose reduction below 7-10 mg/day prednisone 4
• Recurrence rate exceeds 1-2 episodes per year (TINU characteristically shows declining recurrence from 1.7 episodes in year 1 to 0.66 in year 2) 3
• Corticosteroid-related toxicity develops 4

First-Line Immunosuppressive Options

• Methotrexate is the preferred initial disease-modifying agent, achieving remission in approximately 52% of patients with moderate to severe uveitis. 8, 7
• Mycophenolate mofetil (target dose 3 g/day for 6 months) is an alternative first-line option with favorable efficacy/toxicity ratio. 4, 1
• Azathioprine can be used for milder cases or as maintenance therapy. 4, 1

Biologic Therapy for Refractory Disease

• Adalimumab or infliximab should be used for patients failing conventional immunosuppression, with complete remission achieved in 30-85% of patients. 4, 8, 7
• Infliximab provides rapid reduction in inflammation within 2 weeks compared to other agents. 4, 8
• Never use etanercept for TINU syndrome, as it may paradoxically worsen or trigger uveitis episodes. 8, 7

Treatment Duration and Monitoring

• Continue immunosuppression for at least 2 years after achieving inactive disease off topical corticosteroids before attempting to taper. 4, 7
• The mean treatment duration before successful discontinuation is approximately 29.5 months, with remission periods averaging 12.8 months. 3
• Taper topical corticosteroids before systemic therapy when disease is controlled on both, as prolonged topical use causes secondary complications (cataracts, glaucoma). 4

Critical Monitoring Parameters

Renal Surveillance

• Baseline renal function (serum creatinine, eGFR) before treatment initiation 4
• Monitor for pyuria (>5 white blood cells per high-power field), which is present in approximately 60% of TINU cases 4
• Urinary β2-microglobulin is a useful diagnostic and monitoring parameter, though not specific 2
• Some patients remain dialysis-dependent despite treatment (approximately 15% in severe cases) 4

Ophthalmologic Surveillance

• Regular ophthalmologic monitoring to assess anterior chamber cells, flare, and visual acuity 4, 7
• Uveitis recurrence is more common than nephritis recurrence in TINU syndrome, requiring vigilant long-term follow-up. 1, 2
• Monitor for corticosteroid-induced complications including cataracts and glaucoma 4

Common Pitfalls to Avoid

• Do not delay systemic corticosteroids while attempting topical therapy alone in patients with concurrent nephritis, as renal function may deteriorate rapidly. 4, 6
• Do not assume synchronous onset of renal and ocular manifestations—they are typically asynchronous, with uveitis potentially developing months after nephritis. 1, 2
• Do not discontinue immunosuppression prematurely, as TINU characteristically shows limited responsiveness to short corticosteroid courses and frequent relapses. 3, 5
• Exclude other causes of tubulointerstitial nephritis (drug-induced, infection-related) and uveitis (sarcoidosis being the main differential) before confirming TINU diagnosis. 5