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Kidney Week

Abstract: FR-OR64

Urinary Endotrophin Excretion Is Associated with Graft Failure and Mortality in Kidney Transplant Recipients

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Alkaff, Firas F., University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Kremer, Daan, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Thaunat, Olivier, Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Transplantation, Néphrologie et Immunologie Clinique, Lyon, France
  • Berger, Stefan P., University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Van Den Born, Jacob, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Genovese, Federica, Nordic Bioscience, Herlev, Denmark
  • Karsdal, Morten Asser, Nordic Bioscience, Herlev, Denmark
  • Bakker, Stephan J.L., University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Rasmussen, Daniel Guldager Kring, Nordic Bioscience, Herlev, Denmark
  • Tepel, Martin, Odense University Hospital, Department of Nephrology, Odense, Denmark
Background

Kidney fibrosis is a suggested cause of kidney failure and premature mortality, regardless of the underlying cause. Since collagen type VI is closely linked to kidney fibrosis, we aimed to evaluate whether endotrophin, a profibrotic signaling molecule that reflects collagen type VI formation, in the urine was independently associated with graft failure and mortality among kidney transplant recipients (KTR).

Methods

We used data of KTR with a functioning graft ≥ one year that were enrolled in the TransplantLines Biobank and Cohort Study. Endotrophin was measured by the PRO-C6 enzyme-linked immunosorbent assay in the 24h urine.

Results

There were 621 KTR (age 53 ± 13 years old, 43% female, 5.2 [2.0-12.0] years after transplantation, eGFR 45 ± 19 mL/min/1.73 m2) included in the analyses. The 24h urinary endotrophin excretion at baseline was 5.6 [3.1-13.5] µg/24h. During median follow-up of 5.3 years, 70 KTR (11.3%) developed graft failure and 134 KTR (21.6%) died. 24h urinary endotrophin excretion was prospectively associated with both increased risk of graft failure and mortality, independent of potential confounders (Table).

Conclusion

Urinary endotrophin excretion is independently associated with an increased risk of graft failure and mortality in KTR. Further studies with different KTR populations are needed to confirm these findings.

Cox proportional-hazards analyses for the association of 24h urinary endotrophin excretion with graft failure and mortality.
 Graft FailureMortality
ModelHR per doubling (95%CI)p-valueHR per doubling (95%CI)p-value
Crude1.59 (1.44-1.75)<0.0011.26 (1.15-1.37)<0.001
Model 11.63 (1.47-1.80)<0.0011.31 (1.20-1.42)<0.001
Model 21.16 (1.02-1.33)0.0271.19 (1.07-1.33)0.001
Model 31.19 (1.03-1.38)0.0181.17 (1.05-1.30)0.005
Model 41.22 (1.05-1.42)0.0091.16 (1.04-1.29)0.009

Model 1 was adjusted for age, sex, and time after transplantation at inclusion. Model 2 was further adjusted for estimated glomerular filtration rate and log2 24h urinary protein excretion. Model 3 was further adjusted for body mass index and diabetic nephropathy as primary kidney disease. Model 4 was further adjusted for donor age and history of delayed graft function.

Funding

  • Commercial Support – Astellas BV and Chiesi Pharmaceuticals BV