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Abstract: FR-PO773

PRO-C6-Rec: Investigating Circulating Endotrophin as a Biomarker in Kidney Transplantation

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Genovese, Federica, Nordic Bioscience, Herlev, Herlev , Denmark
  • Kremer, Daan, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Alkaff, Firas F., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Bakker, Stephan J.L., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Tepel, Martin, Syddansk Universitet, Odense, Syddanmark, Denmark
  • Thaunat, Olivier, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France
  • van den Born, Jacob, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Karsdal, Morten Asser, Nordic Bioscience, Herlev, Herlev , Denmark
  • Rasmussen, Daniel Guldager Kring, Nordic Bioscience, Herlev, Herlev , Denmark
Background

Novel biomarkers are needed to improve management of kidney transplant recipients. During kidney injury, collagen type VI formation increases. The C-terminal fragment from the alpha3 chain (endotrophin) is released during formation and promotes inflammation and fibrosis. In the Eurostars (Eureka) funded consortium, PRO-C6-Rec, we investigated endotrophin in nine transplant cohorts from three European countries to obtain a comprehensive insight on the ability of this fragment to predict disease progression.

Methods

We analyzed plasma endotrophin with the PRO-C6 ELISA in nine transplant cohorts from three European countries. In incident kidney transplant recipients (KTR), levels were investigated both before and after transplantation, and the association with both acute (delayed graft function and rejection) and long-term outcomes (graft failure and mortality) was investigated. Relevant clinical variables were used to adjust the associations of endotrophin with the investigated outcomes.

Results

Levels of endotrophin in donors of kidney grafts were the same as observed in healthy individuals (7.1 [6.2-8.2] vs 7.8 [7.1-8.3]). Pretransplant endotrophin levels were independently associated with delayed graft function in three independent cohorts (OR [95% CI] per increase in one SD of 1.56 [1.13-2.17], 2.09 [1.30-3.36], and 2.06 [1.43-2.97]). Levels of endotrophin were markedly reduced after transplantation (Figure, p<0.001). KTRs who experienced rejection had significantly higher endotrophin (p<0.001). In prevalent KTRs ≥1 year after transplantation, levels of endotrophin independently predicted both graft failure and all-cause mortality (HR [95% CI] per doubling; 1.87 [1.07-3.28] and 2.59 [1.73-3.87], respectively).

Conclusion

We show that the pro-fibrotic and pro-inflammatory molecule endotrophin is markedly increased in plasma of patients known to have increased risk of outcome, and that endotrophin is an independent predictor of clinically relevant outcomes, likely related to kidney fibrosis and inflammation.

Funding

  • Government Support – Non-U.S.