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F. Mackensen, F. David, Jü. Grulich-Henn, J. T. Rosenbaum, M. D. Becker; Urinary Beta-2 Microglobulin Levels Reveal a High Incidence of Tubulointerstitial Nephritis and Uveitis Syndrome (TINU) in Children With Sudden Onset, Bilateral, Anterior Uveitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3901.
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TINU is a specific form of uveitis that is unfamiliar to most ophthalmologists. In a chart review TINU was present in 32% of patients with bilateral anterior uveitis with sudden onset less than 20 years old. To diagnose TINU, the highest grade of certainty is gained by a positive kidney biopsy. As this is a very invasive procedure less invasive tests are needed. Urinary beta-2microglobulin (Ub2MG) is a marker for tubular dysfunction which has been shown to be elevated in patients with TINU with normal renal function but abnormal renal biopsy (Goda et al).
Beginning January 2006 we prospectively obtained Ub2MG levels in all children (<18 years) with bilateral, sudden onset anterior uveitis attending our pediatric uveitis clinic for the first time. Normal values were defined as less than 0.33 mg/l. Other clinical criteria as defined by Mandeville et al were used to grade the certainty of the diagnosis. We compared with a healthy control group of children with strabismus from the neuroophthalmologic clinic and a group of children with other uveitis subsets.
Ten children with bilateral, sudden onset anterior uveitis attended our clinic since January 2006 (total 59 new children in this time period). We tested nine for Ub2MG; one was excluded because he came with the certain diagnosis of TINU from a nephrologist. Of these nine, 6 showed clinical criteria suggesting possible (n=4) to probable TINU (n=2). In all 6 patients, but one, Ub2MG levels were elevated to a mean value of 0.73 mg/l (SD = 0.55). Conversely, the three patients without clinical criteria for TINU, all had normal Ub2MG levels (mean 0.16 mg/l, SD = 0.08). There was a positive correlation between clinical criteria and Ub2MG levels (Spearman r = 0.68, p=0.05).We determined Ub2MG in 11 healthy children; only two had slightly elevated levels (mean = 0.25 mg/l, SD = 0.13). Of two children with other uveitis subtypes where Ub2MG was obtained, none had elevated levels (0.08 and 0.32 mg/l).
Our preliminary results indicate that TINU may be present in 60% (5+1/10) of children with bilateral, anterior sudden onset uveitis, and 10% (6/59) of all new children with uveitis seen in 11 months, by far a higher number than previously assumed. Ub2MG seems to be an non-invasive diagnostic marker to suggest the diagnosis of TINU. Obviously, this depicts a tertiary referral center and not frequencies in the population.
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