Tubulointerstitial nephritis and uveitis (TINU) is a syndrome involving AIN (kidney inflammation primarily of the interstitium and the tubules with relative sparing of the glomeruli and vasculature), coupled with uveitis. This association was first described by Dobrin and associates in 1975. In 2001, Mandeville and colleagues provided a comprehensive review of the disorder and proposed a set of diagnostic criteria ( Table ). These authors maintain that TINU is a diagnosis of exclusion. Our patient was felt to have TINU since he had histopathologic evidence of AIN, uveitis typical of TINU, and no evidence of another disease that can cause renal pathology and uveitis.
AIN accounts for 10%-25% of people with acute renal failure. It can either be idiopathic or associated with infectious organisms (viruses, group A streptococcus, Yersinia pseudotuberculosis, salmonella, legionella, mycobacteria, toxoplasma, leptospira), immune disorders (sarcoidosis, Sjogren's syndrome, scleroderma, lupus, Still's disease), drugs and toxins (antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], heavy metals), or other systemic diseases (metabolic disorders, hematopoietic infiltrative disorders). It usually presents with a variety of constitutional symptoms including fever, malaise, arthralgias, and myalgias. Laboratory studies are reflective of proximal tubule dysfunction (glycosuria, aminoaciduria, tubular proteinemia, and hypouricemia) and distal tubule dysfunction (distal renal tubular acidosis, hyperkalemia, sodium wasting, and isosthenuria). Typically, the fractional excretion of sodium is greater than 1% (normal 1%-3%) and proteinuria is less than 1.0 g/24 hours (normal 0.0-0.15g/24 hours). Renal biopsy definitively establishes the diagnosis and is characterized by interstitial edema and infiltration of the interstitium by inflammatory cells, without significant involvement of the glomerular and vascular structures. T-cells are frequently involved in the nephritis, indicating an important role of cell-mediated immunity. The association between AIN and uveitis may be a primary disease process affecting both the kidneys and the eyes, or the eyes may be secondarily inflamed as a result of immune reactions generated during renal disease.
There are about 135 reported cases of TINU, most of them in the nephrology literature. This entity is probably underdiagnosed and may account for some cases of "idiopathic" uveitis if the associated interstitial nephritis was not clinically evident or had resolved by the time the intraocular inflammation had developed. Overall, there is a 3:1 female predominance -- although in cases reported since 1990, there is only a 2:1 female predominance. The age of onset of reported cases is between 9 and 74 years, with a median age of 15 years. There are numerous HLA associations, including HLA-A2, A24, DR4, and B27. Mandeville and colleagues identified no significant association with race or geographic location, but they did find an association with a variety of drugs, toxins, infectious agents, and autoimmune disease. They reported antibiotic use in 24% of the patients, NSAID use in 18% of the patients, and preceding gastrointestinal, urinary tract, gynecologic, or respiratory tract infections in several of the patients. Half of the reported cases had no "risk factors" noted. Several patients had serologic evidence of autoantibodies (ANA, anticardiolipin, rheumatoid factor, anti-DNA, and cANCA), and several had family members with autoimmune disease.
Presenting symptoms with relation to the nephritis in patients with TINU include fever (53%), weight loss (47%), fatigue and malaise (44%), anorexia (28%), weakness or asthenia (28%), abdominal or flank pain (28%), arthralgias or myalgias (17%), headache (10%), and polyuria or nocturia (8%).
Mandeville and colleagues noted the prevailing ocular symptoms. They were as follows: eye pain or redness (77%), reduced visual acuity (20%), and photophobia (14%). Eighty percent of the uveitis was anterior uveitis, while 20% was posterior or panuveitis. Uveitis was bilateral in 77% of the cases. Ocular findings may precede (21%), develop concurrently with (15%), or follow (65%) onset of the interstitial nephritis, with the median onset of ocular symptoms 1 month after the onset of systemic symptoms (range -2 to +14 months). In some cases, onset of uveitis accompanied relapse of renal disease, but generally the course of the renal disease is independent of ocular symptoms. Uveitis recurred in 41% of cases with a mean follow-up of 23 months. Intraocular complications were reported in 21% of cases. These included posterior synechiae (68%), optic disc swelling (25%), cystoid macular edema, macular pucker, chorioretinal scar formation, cataract formation, and glaucoma.
There is little data on long-term prognosis, although there are no reported cases of permanent severe vision loss. Visual acuity data are available for only 28 reported eyes, with the initial acuity rarely worse than 20/40. Visual acuity improved to 20/25 or better in almost all cases. Renal disease resolved either spontaneously or with treatment in most patients, and only 2 patients with TINU were documented to require chronic dialysis.
Interstitial nephritis often resolves spontaneously after elimination of the inciting factor, but systemic steroids have been used for more severe cases. Anterior uveitis is generally treated with topical steroids and cycloplegic agents, and less commonly with periocular steroid injection, systemic steroids, or immunomodulatory agents such as methotrexate, azathioprine, or cyclosporine.
Medscape Ophthalmology. 2004;5(1) © 2004 Medscape
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