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

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 beta 2-microglobulin (beta 2M), 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 beta 2M, 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 beta 2M, 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 beta 2M 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 beta 2M levels than patients with normal renal function (median beta 2M, 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 beta 2M combined with increased serum creatinine was 100% for detecting definitive and/or probable TINU syndrome. CONCLUSIONS AND RELEVANCE These data suggest that urinary beta 2M 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 Value of Measuring Urinary beta 2-Microglobulin and Serum Creatinine for Detecting Tubulointerstitial Nephritis and Uveitis Syndrome in Young Patients With Uveitis

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 beta 2-microglobulin (beta 2M), 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 beta 2M, 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 beta 2M, 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 beta 2M 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 beta 2M levels than patients with normal renal function (median beta 2M, 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 beta 2M combined with increased serum creatinine was 100% for detecting definitive and/or probable TINU syndrome. CONCLUSIONS AND RELEVANCE These data suggest that urinary beta 2M 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

Vascular function in children after renal transplantation

Background: Atherosclerotic complications are the main cause of death in adult patients with renal failure. Endothelial dysfunction is a hallmark of early atherosclerotic changes. The numerous risk factors for endothelial dysfunction present in adults are present in children with renal failure, as well. In addition to this, increased stiffness of the arterial tree conveys an increased risk for cardiovascular mortality. The aim of this study is to investigate whether pediatric kidney recipients already show endothelial dysfunction and have increased arterial stiffness. Methods: We investigated 20 pediatric kidney recipients with stable graft function and 20 healthy children. Endothelial function was studied noninvasively with ultrasound and digital signal analysis equipment as the percentage of post-ischemic flow-mediated dilatation (FMD) of the brachial artery. Parameters of arterial distensibility were calculated from distension of the brachial artery during the cardiac cycle, pulse pressure, and baseline diameter. Results: FMD was significantly less in patients (7.7% +/- 5.4%) than controls (15.0% +/- 7.1 %; P <0.001), indicating endothelial dysfunction in pediatric kidney recipients. Impairment of FMD was found predominantly in patients being treated for hypertension. Arterial distensibility was diminished in patients (3.4 +/- 2.8 versus 5.7 +/- 3.3 10(-3)/mm Hg; P <0.02), indicating increased stiffness of the arterial tree. Patients had a greater baseline diameter of the brachial artery adjusted for height than healthy controls at equal blood pressure. Conclusion: These findings suggest arterial wall changes in pediatric renal transplant recipients. They are already at risk for premature development of atherosclerotic complications and cardiovascular mortality

Long-term follow-up of renal transplantation in children: a Dutch cohort study

BACKGROUND: Few data exist on long-term morbidity, overall survival, and graft survival of pediatric renal transplantation. METHODS: The authors performed a long-term cohort study in all Dutch patients, born before 1979, with onset of end-stage renal disease (ESRD) between 1972 and 1992 at age 0 to 15 years. Data on graft survival and determinants of outcome were obtained by reviewing all medical charts. The health status was assessed by cross-sectional examination of surviving patients. RESULTS: Three hundred ninety-seven transplantations were performed in 231 of all 249 patients, of whom 25 died with a functioning graft. Cardiovascular disease was the most prominent cause of death. Graft survival estimates for all transplantations were 59.2%, 45.3%, 35.4%, and 30.3% at 5, 10, 15, and 20 years, respectively. In comparison with azathioprine, cyclosporine as the immunosuppressant was associated with increased graft survival in retransplantations but not in first transplantations. Cross-sectional examination was performed on 110 patients. In 44 patients, the most recent graft survival exceeded 15 years. Co-morbidity was found in 40% of all patients; motor, hearing, or visual disabilities were found in 19%. Bone disease, headaches, itching, and tremors were the most reported disabling problems. Cyclosporine use was associated with hypertension and a history of epilepsy. Compared with all age-matched Dutch inhabitants, the educational attainment was low, and unemployment and parental dependency were high. CONCLUSIONS: The authors' results emphasize the need for reducing cardiovascular disease and metabolic bone disease in pediatric ESRD, a policy toward less toxic antirejection therapy, a more strict treatment of hypertension, and more attention for schooling and social development toward independence