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Abstract
Delayed graft function after kidney transplantation is common and increases morbidity and health care costs. There is evidence that endotrophin, a specific fragment of pro-collagen type VI, promotes the inflammatory response in kidney diseases. We tested the hypothesis that pretransplant endotrophin in kidney transplant recipients may be associated with the risk of delayed graft function. Pretransplant plasma endotrophin was assessed using an enzyme-linked immunosorbent assay in three independent cohorts with 806 kidney transplant recipients. The primary outcome was delayed graft function, i.e., the necessity of at least one dialysis session within one-week posttransplant. In the discovery cohort median pretransplant plasma endotrophin was higher in 32 recipients (12%) who showed delayed graft function when compared to 225 recipients without delayed graft function (58.4 ng/mL [IQR 33.4–69.0]; N = 32; vs. 39.5 ng/mL [IQR 30.6–54.5]; N = 225; P = 0.009). Multivariable logistic regression, fully adjusted for confounders showed, that pretransplant plasma endotrophin as a continuous variable was independently associated with delayed graft function in both validation cohorts, odds ratio 2.09 [95% CI 1.30–3.36] and 2.06 [95% CI 1.43–2.97]. Pretransplant plasma endotrophin, a potentially modifiable factor, was independently associated with increased risk of delayed graft function and may be a new avenue for therapeutic interventions.
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1 Odense University Hospital, Department of Nephrology, Odense, Denmark (GRID:grid.7143.1) (ISNI:0000 0004 0512 5013); University of Southern Denmark, Institute of Molecular Medicine, Cardiovascular and Renal Research, Odense C, Denmark (GRID:grid.10825.3e) (ISNI:0000 0001 0728 0170)
2 University Medical Center Groningen, University of Groningen, Division of Nephrology, Department of Internal Medicine, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598); Faculty of Medicine Universitas Airlangga, Department of Pharmacology and Therapy, Surabaya, Indonesia (GRID:grid.440745.6) (ISNI:0000 0001 0152 762X)
3 University Medical Center Groningen, University of Groningen, Division of Nephrology, Department of Internal Medicine, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598)
4 Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Transplantation, Néphrologie et Immunologie Clinique, Lyon, France (GRID:grid.412180.e) (ISNI:0000 0001 2198 4166)
5 Aarhus University Hospital, Department of Renal Medicine, Aarhus, Denmark (GRID:grid.154185.c) (ISNI:0000 0004 0512 597X); Aarhus University, Department of Clinical Medicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722)
6 Aarhus University, Department of Clinical Medicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722)
7 University of Copenhagen, Biomedical Sciences, Faculty of Health and Medical Science, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X); Nordic Bioscience, Biomarkers and Research, Herlev, Denmark (GRID:grid.436559.8) (ISNI:0000 0004 0410 881X)
8 Nordic Bioscience, Biomarkers and Research, Herlev, Denmark (GRID:grid.436559.8) (ISNI:0000 0004 0410 881X)