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Serum free sulfhydryl status is associated with patient and graft survival in renal transplant recipients

Frenay, A-R. S., de Borst, M. H., Bachtler, M., Tschopp, N., Keyzer, C. A., van den Berg, E., Bakker, S. J. L., Feelisch, M., Pasch, A. & van Goor, H., Oct-2016, In : Free Radical Biology and Medicine. 99, p. 345-351 7 p.

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  • Serum free sulfhydryl status is associated with patient and graft

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DOI

Oxidative stress contributes significantly to graft failure, morbidity and mortality in renal transplant recipients (RTR). In cells, free sulfhydryl groups (reduced thiols, R-SH) are the transducers of redoxregulated events; their oxidation status is modulated by interaction with reactive oxygen and nitrogen oxide species and thought to be in equilibrium with the circulating pool. We hypothesized that high levels of serum free thiols are a reflection of a favorable redox status and therefore positively associated with cardiovascular risk parameters, patient and graft survival in RTR.

To test this, reactive free thiol groups (R-SH; corrected for total protein) were quantified in serum of 695 RTR (57% male, 53 +/- 13 yr, functioning graft >= 1 yr) using Ellman's Reagent, and R-SH determinants were evaluated with multivariable linear regression models. Associations between R-SH and mortality or graft failure were assessed using multivariable Cox regression analyses.

In multivariable models, male gender, estimated glomerular filtration rate and serum thiosulfate positively associated with R-SH while BMI, HbAl c, corrected calcium and NT-pro-BNP inversely associated with R-SH (model R-2=0.26). During follow-up (3.1 [2.7-3.9] yrs), 79 (11%) patients died and 45 (7%) patients developed graft failure. R-SH correlated inversely with all-cause mortality (HR 0.58 [95% CI 0.45-0.75] per SD increase) and graft failure (HR 0.42 [0.30-0.59]; both P <0.001), independent of parameters with which R-SH significantly associated in the multivariable regression analyses, except for NT-pro-BNP.

Serum R-SH are associated with a beneficial cardiovascular risk profile and better patient and graft survival in RTR, suggesting potential usefulness as low-cost, high-throughput screening tool for whole body redox status in translational studies. Whether R-SH modification improves long-term outcome of RTR warrants further exploration. (C) 2016 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)345-351
Number of pages7
JournalFree Radical Biology and Medicine
Volume99
Publication statusPublished - Oct-2016

    Keywords

  • Cardiovascular disease, Free thiols, Graft failure, Kidney transplantation, Mortality, Oxidative stress, CARDIOVASCULAR-DISEASE, NITRIC-OXIDE, KIDNEY-TRANSPLANTATION, BLOOD-PRESSURE, MORTALITY, MECHANISMS, IMPACT, THIOLS, ACID
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  1. TransplantLines

    Bakker, S. (Creator), Leuvenink, H. (Creator), Porte, R. (Creator), University of Groningen, 2017

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ID: 35019693