Ymkje M Hettinga1, Laura M E Scheerlinck1, Marc R Lilien2, Aniki Rothova3, Joke H de Boer1. 1. Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands. 2. Department of Pediatric Nephrology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands. 3. Department of Ophthalmology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
Abstract
IMPORTANCE: Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by tubulointerstitial and ocular inflammation. Thus far, the value of noninvasive diagnostic tests is not known. OBJECTIVE: To determine whether urinary β2-microglobulin (β2M), urinary protein, and serum creatinine have predictive value for detecting TINU syndrome in young patients with uveitis. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted July 2010 through February 2013 at a tertiary care referral center in Utrecht, the Netherlands. Forty-five consecutive new patients with uveitis aged 22 years or younger were enrolled. EXPOSURES: Urinary β2M, urinary protein, and serum creatinine were measured prospectively, and the estimated glomerular filtration rate was calculated. MAIN OUTCOMES AND MEASURES: A post hoc analysis was performed to determine whether urinary β2M, urinary protein, serum creatinine, estimated glomerular filtration rate, and/or pyuria were correlated with definitive and probable cases of TINU syndrome. RESULTS: Eighteen of the 45 patients (40%) in our cohort had elevated urinary β2M levels, and 10 patients (22%) had elevated serum creatinine levels. Twenty of 43 patients (47%) had proteinuria. Eight of the 45 patients were diagnosed by a pediatric nephrologist as having renal dysfunction that suggested acute interstitial nephritis. Of these 8 patients, 2 were definitively diagnosed as having TINU syndrome (confirmed by renal biopsy). After excluding other causes of renal dysfunction, the remaining 6 patients with uveitis and renal dysfunction fulfilled the criteria of probable TINU syndrome. The 8 patients with definitive or probable TINU syndrome had higher urinary β2M levels than patients with normal renal function (median β2M, 1.95 mg/L; 95% CI, 1.26-5.16 mg/L vs 0.20 mg/L; 95% CI, 0.19-0.21 mg/L; P < .001; Mann-Whitney U test). Our analysis revealed that the positive predictive value of increased β2M combined with increased serum creatinine was 100% for detecting definitive and/or probable TINU syndrome. CONCLUSIONS AND RELEVANCE: These data suggest that urinary β2M and serum creatinine levels are sensitive and relatively simple diagnostic screening tools for detecting renal dysfunction to diagnose TINU syndrome in young patients with uveitis similar to those evaluated in this study.
IMPORTANCE: Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by tubulointerstitial and ocular inflammation. Thus far, the value of noninvasive diagnostic tests is not known. OBJECTIVE: To determine whether urinary β2-microglobulin (β2M), urinary protein, and serum creatinine have predictive value for detecting TINU syndrome in young patients with uveitis. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted July 2010 through February 2013 at a tertiary care referral center in Utrecht, the Netherlands. Forty-five consecutive new patients with uveitis aged 22 years or younger were enrolled. EXPOSURES: Urinary β2M, urinary protein, and serum creatinine were measured prospectively, and the estimated glomerular filtration rate was calculated. MAIN OUTCOMES AND MEASURES: A post hoc analysis was performed to determine whether urinary β2M, urinary protein, serum creatinine, estimated glomerular filtration rate, and/or pyuria were correlated with definitive and probable cases of TINU syndrome. RESULTS: Eighteen of the 45 patients (40%) in our cohort had elevated urinary β2M levels, and 10 patients (22%) had elevated serum creatinine levels. Twenty of 43 patients (47%) had proteinuria. Eight of the 45 patients were diagnosed by a pediatric nephrologist as having renal dysfunction that suggested acute interstitial nephritis. Of these 8 patients, 2 were definitively diagnosed as having TINU syndrome (confirmed by renal biopsy). After excluding other causes of renal dysfunction, the remaining 6 patients with uveitis and renal dysfunction fulfilled the criteria of probable TINU syndrome. The 8 patients with definitive or probable TINU syndrome had higher urinary β2M levels than patients with normal renal function (median β2M, 1.95 mg/L; 95% CI, 1.26-5.16 mg/L vs 0.20 mg/L; 95% CI, 0.19-0.21 mg/L; P < .001; Mann-Whitney U test). Our analysis revealed that the positive predictive value of increased β2M combined with increased serum creatinine was 100% for detecting definitive and/or probable TINU syndrome. CONCLUSIONS AND RELEVANCE: These data suggest that urinary β2M and serum creatinine levels are sensitive and relatively simple diagnostic screening tools for detecting renal dysfunction to diagnose TINU syndrome in young patients with uveitis similar to those evaluated in this study.
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