Elevated plasma free thiols are associated with early and one-year graft function in renal transplant recipients

Marie B Nielsen; Bente Jespersen; Henrik Birn; Nicoline V Krogstrup; Arno R Bourgonje; Henri G D Leuvenink; Harry van Goor; Rikke Nørregaard

doi:10.1371/journal.pone.0255930

Elevated plasma free thiols are associated with early and one-year graft function in renal transplant recipients

PLoS One. 2021 Aug 11;16(8):e0255930. doi: 10.1371/journal.pone.0255930. eCollection 2021.

Authors

Marie B Nielsen^{1

2}, Bente Jespersen^{1

3}, Henrik Birn^{1

2}, Nicoline V Krogstrup^{1

4}, Arno R Bourgonje⁵, Henri G D Leuvenink⁶, Harry van Goor⁷, Rikke Nørregaard³

Affiliations

¹ Department of Renal Medicine, Aarhus University Hospital, Aarhus N, Denmark.
² Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
³ Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark.
⁴ Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
⁵ Department of Gastroenterology and Hepatology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
⁶ Department of Surgery, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
⁷ Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.

Abstract

Background: Reduced free thiols in plasma are indicative of oxidative stress, which is an important contributor to ischaemia-reperfusion injury (IRI) in kidney transplantation leading to kidney damage and possibly delayed graft function (DGF). In a post-hoc, exploratory analysis of the randomised controlled CONTEXT trial, we investigated whether higher (i.e. less oxidised) plasma levels of free thiols as a biomarker of reduced oxidative stress are associated with a better initial graft function or a higher GFR.

Methods: Free thiol levels were measured in plasma at baseline, 30 and 90 minutes after reperfusion of the kidney as well as at Day 1, Day 5 and twelve months after kidney transplantation in 217 patients from the CONTEXT study. Free thiol levels were compared to the kidney graft function measured as the estimated time to a 50% reduction in plasma creatinine (tCr50), the risk of DGF and measured GFR (mGFR) at Day 5 and twelve months after transplantation.

Results: Higher levels of free thiols at Day 1 and Day 5 are associated with higher mGFR at Day 5 (p<0.001, r2adj. = 0.16; p<0.001, r2adj. = 0.25), as well as with mGFR at twelve months (p<0.001, r2adj. = 0.20; p<0.001, r2adj. = 0.16). However, plasma levels of free thiols at 30 minutes and 90 minutes, but not Day 1, were significantly higher among patients experiencing DGF.

Conclusion: Higher levels of plasma free thiols at Day 1 and Day 5, which are reflective of lower levels of oxidative stress, are associated with better early and late graft function in recipients of a kidney graft from deceased donors.

Trial registration: ClinicalTrials.gov Identifier: NCT01395719.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Creatinine / blood
Double-Blind Method
Female
Glomerular Filtration Rate
Humans
Kidney / physiopathology*
Kidney Failure, Chronic / therapy
Kidney Transplantation*
Male
Middle Aged
Sulfhydryl Compounds / blood*
Transplant Recipients

Substances

Sulfhydryl Compounds
Creatinine

Associated data

ClinicalTrials.gov/NCT01395719

Grants and funding

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