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

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Graph showing the level of…
Fig 1. Graph showing the level of free thiols (μM) measured at baseline over the total study period (p = 0.76).
Fig 2. Simple linear regression of plasma…
Fig 2. Simple linear regression of plasma free thiols and mGFR at Day 5.
A) Free thiols at Day 1. B) Free thiols at Day 5.
Fig 3. Box plot of the level…
Fig 3. Box plot of the level of free thiols (μM) at different time points and delayed graft function (DGF).

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