The Value of Measuring Urinary β2-Microglobulin and Serum Creatinine for Detecting Tubulointerstitial Nephritis and Uveitis Syndrome in Young Patients With Uveitis | Nephrology | JAMA Ophthalmology | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.173.234.169. Please contact the publisher to request reinstatement.
1.
Dobrin  RS, Vernier  RL, Fish  AL.  Acute eosinophilic interstitial nephritis and renal failure with bone marrow-lymph node granulomas and anterior uveitis: a new syndrome.  Am J Med. 1975;59(3):325-333.PubMedGoogle ScholarCrossref
2.
Mandeville  JT, Levinson  RD, Holland  GN.  The tubulointerstitial nephritis and uveitis syndrome.  Surv Ophthalmol. 2001;46(3):195-208.PubMedGoogle ScholarCrossref
3.
Kump  LI, Cervantes-Castañeda  RA, Androudi  SN, Foster  CS.  Analysis of pediatric uveitis cases at a tertiary referral center.  Ophthalmology. 2005;112(7):1287-1292.PubMedGoogle ScholarCrossref
4.
Rosenbaum  JT.  Bilateral anterior uveitis and interstitial nephritis.  Am J Ophthalmol. 1988;105(5):534-537.PubMedGoogle ScholarCrossref
5.
Goda  C, Kotake  S, Ichiishi  A, Namba  K, Kitaichi  N, Ohno  S.  Clinical features in tubulointerstitial nephritis and uveitis (TINU) syndrome.  Am J Ophthalmol. 2005;140(4):637-641.PubMedGoogle ScholarCrossref
6.
Jahnukainen  T, Ala-Houhala  M, Karikoski  R, Kataja  J, Saarela  V, Nuutinen  M.  Clinical outcome and occurrence of uveitis in children with idiopathic tubulointerstitial nephritis.  Pediatr Nephrol. 2011;26(2):291-299.PubMedGoogle ScholarCrossref
7.
Bloch-Michel  E, Nussenblatt  RB.  International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease.  Am J Ophthalmol. 1987;103(2):234-235.PubMedGoogle ScholarCrossref
8.
Blufpand  HN, Westland  R, van Wijk  JA, Roelandse-Koop  EA, Kaspers  GJ, Bökenkamp  A.  Height-independent estimation of glomerular filtration rate in children: an alternative to the Schwartz equation.  J Pediatr. 2013;163(6):1722-1727.PubMedGoogle ScholarCrossref
9.
Florkowski  CM, Chew-Harris  JS.  Methods of estimating GRF: different equations including CKD-EPI.  Clin Biochem Rev. 2011;32(2):75-79.PubMedGoogle Scholar
10.
Agresti  A.  Dealing with discreteness: making ‘exact’ confidence intervals for proportions, differences of proportions, and odds ratios more exact.  Stat Methods Med Res. 2003;12(1):3-21.PubMedGoogle ScholarCrossref
11.
Petty  RE, Southwood  TR, Manners  P,  et al; International League of Associations for Rheumatology.  International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001.  J Rheumatol. 2004;31(2):390-392.PubMedGoogle Scholar
12.
Holland  GN, Denove  CS, Yu  F.  Chronic anterior uveitis in children: clinical characteristics and complications.  Am J Ophthalmol. 2009;147(4):667-678, e5.PubMedGoogle ScholarCrossref
13.
Kalinina Ayuso  V, de Boer  JH, Byers  HL,  et al.  Intraocular biomarker identification in uveitis associated with juvenile idiopathic arthritis.  Invest Ophthalmol Vis Sci. 2013;54(5):3709-3720.PubMedGoogle ScholarCrossref
14.
Izzedine  H, Bodaghi  B, Launay-Vacher  V, Deray  G.  Eye and kidney: from clinical findings to genetic explanations.  J Am Soc Nephrol. 2003;14(2):516-529.PubMedGoogle ScholarCrossref
15.
Izzedine  H, Buhaescu  I, Bodaghi  B,  et al.  Oculo-renal disorders in infectious diseases.  Int Ophthalmol. 2004;25(5-6):299-319.PubMedGoogle ScholarCrossref
16.
Izzedine  H.  Tubulointerstitial nephritis and uveitis syndrome (TINU): a step forward to understanding an elusive oculorenal syndrome.  Nephrol Dial Transplant. 2008;23(4):1095-1097.PubMedGoogle ScholarCrossref
17.
Reddy  AK, Hwang  YS, Mandelcorn  ED, Davis  JL.  HLA-DR, DQ class II DNA typing in pediatric panuveitis and tubulointerstitial nephritis and uveitis.  Am J Ophthalmol. 2014;157(3):678-686, e1-e2.PubMedGoogle ScholarCrossref
18.
Mackensen  F, David  F, Schwenger  V,  et al.  HLA-DRB1*0102 is associated with TINU syndrome and bilateral, sudden-onset anterior uveitis but not with interstitial nephritis alone.  Br J Ophthalmol. 2011;95(7):971-975.PubMedGoogle ScholarCrossref
19.
Levinson  RD, Park  MS, Rikkers  SM,  et al.  Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome.  Invest Ophthalmol Vis Sci. 2003;44(2):653-657.PubMedGoogle ScholarCrossref
20.
Mackensen  F, Billing  H.  Tubulointerstitial nephritis and uveitis syndrome.  Curr Opin Ophthalmol. 2009;20(6):525-531.PubMedGoogle ScholarCrossref
21.
Saarela  V, Nuutinen  M, Ala-Houhala  M, Arikoski  P, Rönnholm  K, Jahnukainen  T.  Tubulointerstitial nephritis and uveitis syndrome in children: a prospective multicenter study.  Ophthalmology. 2013;120(7):1476-1481.PubMedGoogle ScholarCrossref
Original Investigation
February 2015

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

Author Affiliations
  • 1Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands
  • 2Department of Pediatric Nephrology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
  • 3Department of Ophthalmology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
JAMA Ophthalmol. 2015;133(2):140-145. doi:10.1001/jamaophthalmol.2014.4301
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.

×