title: Uromodulin in renal transplant recipients: elevated urinary levels and bimodal association with graft failure.
abstract: BACKGROUND
  Urinary uromodulin (UMOD) predicts renal prognosis in native kidneys, but data are conflicting. We investigated its prognostic impact for graft failure (GF) in renal transplant recipients (RTR; n = 600).
  
  
  METHODS
  UMOD concentration was measured cross-sectionally in RTR at 6.0 years [2.6-11.4] post-transplant, in matched patients with native chronic kidney disease (CKD) and healthy subjects. In 59 cases, RTR allograft biopsies were reviewed.
  
  
  RESULTS
  During a follow-up of 5.3 years [4.5-5.7], GF had occurred in 7% of RTR. Median UMOD excretion (mg/24 h) was 20.4 in RTR, 11.6 in CKD and 5.7 in controls (p < 0.001). There was a curvilinear association between UMOD excretion and baseline renal function (p < 0.003) and death-censored GF, with 5.5, 11.5 and 4.0% of the cases in subsequent UMOD excretion tertiles, respectively (p = 0.002). On multivariate Cox regression analysis, hazard ratios for GF for the 1st and 3rd tertiles were 0.37 (p = 0.01) and 0.21 (p = 0.001), respectively. Interstitial fibrosis and tubular atrophy were more severe in the middle tertile (p = 0.007).
  
  
  CONCLUSIONS
  Urinary UMOD is elevated in RTR and associated with graft function, morphology and outcome in a bimodal fashion. Dissection of the disparate mechanisms of GF prediction by urinary UMOD might provide new clues for its alleged pathogenetic significance in progressive renal function loss.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Reznichenko
authors.forename: Marcory C R F
authors.initials: MC
authors.lastname: van Dijk
authors.forename: Jaap Homan
authors.initials: JH
authors.lastname: van der Heide
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Marc
authors.initials: M
authors.lastname: Seelen
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D017211:Treatment Failure; D058949:Uromodulin / Q000652:urine*
chemical_list: D058949:Uromodulin