A unique subset of patients with interstitial nephritis has the TINU syndrome (tubulointerstitial nephritis and uveitis). First described in 1975 , more than 250 cases have now been reported [2,3]. The majority of cases have been documented in the ophthalmology and pediatric nephrology literature via case reports and small descriptive series.
The underlying mechanisms for TINU are not well understood. Limited data suggest that modified C-reactive protein, (mCRP), an autoantigen common to both the uvea and renal tubular cells, may be involved in the pathogenesis . In a study of 97 patients with various renal disorders and 40 healthy controls, the prevalence of immunoglobulin G (IgG) antibodies directed against mCRP was significantly higher among nine patients with TINU syndrome (100 percent) than among those with Sjögren’s associated interstitial nephritis (29 percent), drug induced interstitial nephritis (36 percent), glomerulonephritis (5 percent), and healthy controls (0 percent) . Another study by the same group confirmed that the mCRP is higher among patients with TINU syndrome and late-onset uveitis compared with those with drug-induced interstitial nephritis .
The inflammation in TINU syndrome is thought to be T-lymphocyte driven based upon the histologic findings. In contrast, immune cells in patients with TINU syndrome have a paradoxical suppression of cytokine production and a decrease in peripheral immune response, as demonstrated by anergy to skin testing. This paradox is not unique to TINU as the presence of increased tissue inflammation with concomitant suppression of peripheral immunity is also seen in patients with sarcoidosis [5,6].
RISK FACTORS AND ASSOCIATIONS
No identifiable risk factors have been found in at least 50 percent of cases. In some instances, prior infection or the use of specific drugs (antibiotics to treat upper respiratory infections and nonsteroidal antiinflammatory drugs [NSAIDs]) has been implicated [3,7]. The Chinese herb, "goreisan," has been associated in a case report . Although causality is unclear, concurrent Chlamydia and Epstein-Barr virus infections have been described [9,10]. TINU syndrome has also been reported in patients with autoimmune diseases like hypoparathyroidism , thyroid disease [3,12], IgG4-related autoimmune disease , and rheumatoid arthritis [11,14].
Most patients with TINU are adolescents and young women, with a median age of 15 years . It has also been reported in adults and older adults [16,17]. All series report a female-to-male predominance [3,7], with no particular racial affinity.