Elevated plasma free thiols are associated with early and one-year graft function in renal transplant recipients
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.
CET Conclusion
| Reviewer: | Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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| Conclusion: | This post-hoc analysis of samples from the CONTEXT RCT investigates the correlation between plasma free thiols (a marker of oxidative stress) and post-transplant outcomes. The authors find that free thiol levels at day 1 and 5 correlate significantly with 12-month measured GFR. Whilst the correlations are significant, the R-squared values are fairly low (around 0.2) suggesting limited predictive performance. It is therefore unclear how useful this would be as a tool in clinical practice, or indeed how measurement would help guide clinical care of patients to improve outcomes. |
Study Details
| Aims: | This post-hoc analysis of the randomised controlled CONTEXT trial examines whether higher levels of plasma free thiols as a marker of reduced oxidative stress is linked to better posttransplant outcomes. |
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| Interventions: | Participants in the CONTEXT trial were randomised to either the remote ischaemic conditioning (RIC) group or the sham-RIC group. |
| Participants: | 217 kidney transplant patients who participated in the CONTEXT trial. |
| Outcomes: | Estimated time to a 50% reduction in plasma creatinine (tCr50), delayed graft function and measured glomerular filtration rate (mGFR). |
| Follow Up: | 12 months |
Metadata
| Funding: | Non-industry funding |
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| Publication type: | Randomized Controlled Trial, Randomised Controlled Trial |
| Trial registration: | ClinicalTrials.gov - NCT01395719 |
| Organ: | Kidney |
| Language: | English |
| Author email: | h.van.goor@umcg.nl |
| MeSH terms: | Aged; Creatinine; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Sulfhydryl Compounds; Transplant Recipients; 0 (Sulfhydryl Compounds); AYI8EX34EU (Creatinine) |