The Value of Measuring Urinary β2-Microglobulin and Serum Creatinine for Detecting Tubulointerstitial Nephritis and Uveitis Syndrome in Young Patients With Uveitis

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 PARTICIPANTSThis 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 MEASURESA 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.

The ratio of urinary α1-microglobulin to microalbumin can be used as a diagnostic criterion for tubuloproteinuria

“…The diagnosis of TIN or TINU is difficult because of variable and nonspecific clinical manifestations. Studies have reported that urinary α1-microglobulin and β2-microglobulin excretion increase in patients with TINU (20,21). The current results indicated that urinary α1-microglobin increased significantly (about 100-fold above the upper limit of the normal range) in the 6 patients with ATIN and in the 4 patients with TINU, and the ratio of urinary α1-microglobulin to microalbumin was greater than 1.…”

Challenges of Diagnosing Viral Anterior Uveitis

“…17 Uveitis in TINU syndrome has mostly a chronic bilateral course and is frequently classified as AU in the literature, however vitritis may be prominent. 18,19 Definitive diagnosis of TINU syndrome is based on histopathological examination of renal tissue. However, renal biopsy is not being performed in mild cases, because of the associated risks.…”

“…16 The combination of urinary β-2 microglobulin and serum creatinine is a relatively simple screening tool for renal dysfunction in order to diagnose probable TINU syndrome in young patients with uveitis. 18 …”

Uveitis in Children and Adolescents

“…60 Chronic or recurrent inflammation develops in ≥50% of cases, often requiring long-term immunosuppression. The prognosis tends to be good with prompt and adequate therapy.…”

“…In addition to TINU, the main diagnoses to consider in children and adolescents with both uveitis and renal disease include systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, and Sjögren syndrome. 60 Petrushkin et al 45 provided a systematic overview of the pathogenesis, clinical features, and treatment of familial Mediterranean fever (FMF), a recessively inherited, multisystem, autoinflammatory disease that affects children from the Mediterranean basinmost notably those with Turkish, Armenian, Arabic, and Sephardic Jewish ancestry. Genetic polymorphisms associated with FMF occur in the MEFV (Mediterranean fever) gene, located on chromosome 16 and now known to code for pyrin-a 781 amino acid protein with incompletely understood roles in the regulation of the cellular cytoskeleton, apoptosis, and activation of intracellular pathways involved in inflammatory cytokine signaling.…”