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  • Title: Uromodulin in renal transplant recipients: elevated urinary levels and bimodal association with graft failure.
    Author: Reznichenko A, van Dijk MC, van der Heide JH, Bakker SJ, Seelen M, Navis G.
    Journal: Am J Nephrol; 2011; 34(5):445-51. PubMed ID: 21968132.
    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.
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