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Abstract: FR-PO810

Urinary Copper Excretion Is Associated With Graft Failure in Kidney Transplant Recipients

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Yepes Calderon, Manuela, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Kremer, Daan, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Knobbe, Tim J., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Luersen, Kai, Christian-Albrechts-Universitat zu Kiel Institut fur Humanernahrung und Lebensmittelkunde, Kiel, Schleswig-Holstein, Germany
  • Eisenga, Michele F., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • De Borst, Martin H., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Navis, Gerjan, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Rimbach, Gerald, Christian-Albrechts-Universitat zu Kiel Institut fur Humanernahrung und Lebensmittelkunde, Kiel, Schleswig-Holstein, Germany
  • Bakker, Stephan J.L., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Group or Team Name

  • TransplantLines Investigators
Background

Urinary copper (Cu) excretion increases with the development of proteinuria due to an increase in excretion of Cu carries. This Cu overload is proposed to enhance nephropathy through tubular damage. We aimed to assess whether in kidney transplant recipients (KTR) proteinuria is associated with urinary Cu excretion. Furthermore, if urinary Cu excretion is associated with the biomarker of tubular damage urinary liver-type fatty acid-binding protein (u-LFABP) and with graft failure development.

Methods

In this prospective cohort study, KTR with a functioning allograft ≥1 year were recruited. Urinary Cu was measured in 24-hours urine samples by coupled plasma mass spectrometry. Multivariable linear regression and Cox regression analyses were performed.

Results

In 693 KTR (57% men, 53 ± 13 years old), baseline Cu excretion was 23.57 [Interquartile range (IQR) 11.32–15.87] µg. Cu was directly associated with proteinuria (Std β 0.45, P<0.001) independent of graft function and with u-LFABP (Std β 0.34, P<0.001) independent of proteinuria. During a median follow-up of 5.3 years, 83 (12%) KTR developed GF. Being on the third tertile of urinary Cu excretion was associated with an increased risk of GF (HR 2.94 [95% CI 1.34–6.45]; P < 0.001) independent of adjustment by multiple potential confounders. u-LFABP significantly mediated this association accounting for 46% of the total effect.

Conclusion

We concluded that in KTR proteinuria is associated with increased Cu excretion and this is further associated with the risk of graft failure apparently by enhancing tubular damage. Further studies seem warranted to elucidate whether Cu-targeted interventions may decrease the burden of GF in KTR.

Urinary Copper excretion and graft failure. Model 1: adjustment for age, sex, eGFR, proteinuria, 24-hours urinary volume, and u-LFABP. Model 2: Model 1 + pre-emptive transplantation, transplant vintage, donor type, donor age, donor sex, and HLA mismatch. Model 3: Model 1 + prednisolone cumulative dose, use of calcineurin inhibitors and proliferation inhibitors, and acute rejection treatment.

Funding

  • Government Support – Non-U.S.