Endotrophin Levels Are Associated with Allograft Outcomes in Kidney Transplant Recipients

Author:

Sparding Nadja12ORCID,Genovese Federica1ORCID,Rasmussen Daniel Guldager Kring1ORCID,Karsdal Morten A.1,Krogstrup Nicoline V.3,Nielsen Marie Bodilsen34,Hornum Mads5ORCID,Nagarajah Subagini67,Birn Henrik348,Jespersen Bente38ORCID,Tepel Martin67,Nørregaard Rikke8ORCID,

Affiliation:

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.

Funder

the Danish Council for Independent Research

the Danish Society of Nephrology

the Lundbeck Foundation

the Novo Nordic Foundation

Nyreforeningen

A.P. Møller og hustru Chastine Mc-Kinney Møllers Fond til Almene Formaal

Swedish Medical Association

Aarhus University

Aarhus University Hospital

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

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