Endotrophin Levels Are Associated with Allograft Outcomes in Kidney Transplant Recipients

Nadja Sparding; Federica Genovese; Daniel Guldager Kring Rasmussen; Morten A Karsdal; Nicoline V Krogstrup; Marie Bodilsen Nielsen; Mads Hornum; Subagini Nagarajah; Henrik Birn; The Context Study Group; Bente Jespersen; Martin Tepel; Rikke Nørregaard

doi:10.3390/biom13050792

Endotrophin Levels Are Associated with Allograft Outcomes in Kidney Transplant Recipients

Biomolecules. 2023 May 5;13(5):792. doi: 10.3390/biom13050792.

Authors

Nadja Sparding^{1

2}, Federica Genovese¹, Daniel Guldager Kring Rasmussen¹, Morten A Karsdal¹, Nicoline V Krogstrup³, Marie Bodilsen Nielsen^{3

4}, Mads Hornum⁵, Subagini Nagarajah^{6

7}, Henrik Birn^{3

4

8}, The Context Study Group, Bente Jespersen^{3

8}, Martin Tepel^{6

7}, Rikke Nørregaard⁸

Affiliations

¹ Nordic Bioscience, 2730 Herlev, Denmark.
² Biomedical Sciences, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark.
³ Department of Renal Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.
⁴ Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
⁵ Department of Nephrology, Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
⁶ Department of Nephrology, Odense University Hospital, 5000 Odense, Denmark.
⁷ Institute of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, 5000 Odense, Denmark.
⁸ Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark.

Abstract

Early prediction of kidney graft function may assist clinical management, and for this, reliable non-invasive biomarkers are needed. We evaluated endotrophin (ETP), a novel non-invasive biomarker of collagen type VI formation, as a prognostic marker in kidney transplant recipients. ETP levels were measured with the PRO-C6 ELISA in the plasma (P-ETP) of 218 and urine (U-ETP/Cr) of 172 kidney transplant recipients, one (D1) and five (D5) days, as well as three (M3) and twelve (M12) months, after transplantation. P-ETP and U-ETP/Cr at D1 (P-ETP AUC = 0.86, p < 0.0001; U-ETP/Cr AUC = 0.70, p = 0.0002) were independent markers of delayed graft function (DGF) and P-ETP at D1 had an odds ratio of 6.3 (p < 0.0001) for DGF when adjusted for plasma creatinine. The results for P-ETP at D1 were confirmed in a validation cohort of 146 transplant recipients (AUC = 0.92, p < 0.0001). U-ETP/Cr at M3 was negatively associated with kidney graft function at M12 (p = 0.007). This study suggests that ETP at D1 can identify patients at risk of delayed graft function and that U-ETP/Cr at M3 can predict the future status of the allograft. Thus, measuring collagen type VI formation could aid in predicting graft function in kidney transplant recipients.

Keywords: biomarkers; delayed graft function; fibrosis; kidney failure; kidney transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allografts
Collagen Type VI
Delayed Graft Function / etiology
Humans
Kidney Transplantation* / adverse effects
Risk Factors
Transplant Recipients

Substances

endotrophin
Collagen Type VI

Grants and funding

The authors thank for the financial support for the CONTEXT study of the Danish Council for Independent Research, the Danish Society of Nephrology, the Lundbeck Foundation, the Novo Nordic Foundation, Nyreforeningen (the Danish kidney patient association), A.P. Møller og hustru Chastine Mc-Kinney Møllers Fond til Almene Formaal, Swedish Medical Association, Aarhus University, and Aarhus University Hospital.