TINU syndrome is defined by the combination of tubulointerstitial nephritis and uveitis. First described in 1975, most cases have been documented via case reports and small descriptive series.
The pathogenesis of TINU syndrome is unknown. Limited evidence suggests that an autoantigen to modified C-reactive protein (mCRP) may underlie the pathogenesis of the disease. Delayed-type hypersensitivity and suppressed cell-mediated immunity, with a predominance of T-lymphocytes, likely also play a significant role. Proliferation and activation of T-lymphocytes by interleukin-2 (IL-2) have been implicated.
●Possible risk factors include prior infection or the use of specific drugs (antibiotics and nonsteroidal anti-inflammatory drugs [NSAIDs]). The Chinese herb, "goreisan," and concurrent Chlamydia and Epstein-Barr virus infections have been associated in case reports. TINU syndrome has also been reported in patients with autoimmune diseases like hypoparathyroidism, thyroid disease, IgG4-related autoimmune disease, and rheumatoid arthritis.
●Most patients with TINU are adolescents and young women, although it has been reported in adults and older adults. There is a female-to-male predominance, with no particular racial affinity. There may be an association with HLA-DQA1*01, HLA-DQB1*05, and HLA-DQB1*01.
●TINU may be associated with systemic findings including fever, weight loss, fatigue, malaise, anorexia, asthenia, abdominal and flank pain, arthralgias, myalgias, headache, polyuria, and/or nocturia.
●Renal manifestations include flank pain, sterile pyuria, hematuria, proteinuria (usually subnephrotic range), renal insufficiency, and acute renal failure (ARF). Proximal and distal tubular defects can be seen, resulting in aminoaciduria, glucosuria, phosphaturia, and acidification defects. Renal sonography may demonstrate marked swelling of the kidneys.
●Patients with uveitis usually present with bilateral eye pain or redness accompanied by photophobia and decreased visual acuity, usually after the onset of renal disease.
●Laboratory findings include eosinophilia, anemia, slightly abnormal liver function tests, and an elevated erythrocyte sedimentation rate (ESR). TINU syndrome has been associated with antineutrophil cytoplasmic antibody (ANCA); antinuclear antibody (ANA), an autoantibody directed against renal tubular cells; rheumatoid factor (RF); and hypocomplementemia.
●The diagnosis of TINU syndrome is suggested by the combination of uveitis and renal involvement, with renal biopsy consistent with acute interstitial nephritis. The differential diagnosis includes sarcoidosis, Sjögren's syndrome, systemic lupus erythematosus, Wegener's granulomatosis, Behçet’s syndrome, and infectious diseases such as tuberculosis, brucellosis, toxoplasmosis, and histoplasmosis. The distinction of TINU syndrome from sarcoidosis and Sjögren's syndrome is particularly difficult.
●Renal disease in patients with TINU is usually variable. Patients with progressive renal insufficiency are typically treated with prednisone at a dose of 1 mg/kg per day (typically between 40 to 60 mg/day) for three to six months (with the duration of therapy dependent upon the response) and then slowly tapered. The optimal management of the patient with uveitis requires early referral to and management by an ophthalmologist.