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

Serum free sulfhydryl status is associated with patient and graft survival in renal transplant recipients
Serum free sulfhydryl status is associated with patient and graft survival in renal transplant recipients
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 redox-regulated 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±13yr, functioning graft ?1yr) 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, HbA1c, 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.
0891-5849
345-351
Frenay, Anne-Roos S.
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de Borst, Martin H.
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Bachtler, Matthias
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Tschopp, Nadine
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Keyzer, Charlotte A.
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van den Berg, Else
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Bakker, Stephan J.L.
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Feelisch, Martin
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Pasch, Andreas
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van Goor, Harry
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Frenay, Anne-Roos S.
314506f7-a54f-4950-88fa-d22db328ab1d
de Borst, Martin H.
52a640c9-eb91-497f-84e8-5f3d31e9481d
Bachtler, Matthias
e84b3d87-6978-48da-be8e-49bcdf1f8ca1
Tschopp, Nadine
6169630c-cdf7-4842-b214-31d45da0db3b
Keyzer, Charlotte A.
3d9f58dc-2988-4496-8cb7-62fd3b8e70f3
van den Berg, Else
711eedae-261a-4ecf-86f4-295617ce1d95
Bakker, Stephan J.L.
90f2f27b-610c-4278-b129-d2405f4bda2e
Feelisch, Martin
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Pasch, Andreas
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van Goor, Harry
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Frenay, Anne-Roos S., de Borst, Martin H., Bachtler, Matthias, Tschopp, Nadine, Keyzer, Charlotte A., van den Berg, Else, Bakker, Stephan J.L., Feelisch, Martin, Pasch, Andreas and van Goor, Harry (2016) Serum free sulfhydryl status is associated with patient and graft survival in renal transplant recipients. Free Radical Biology & Medicine, 99, 345-351. (doi:10.1016/j.freeradbiomed.2016.08.024). (PMID:27554970)

Record type: Article

Abstract

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 redox-regulated 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±13yr, functioning graft ?1yr) 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, HbA1c, 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.

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Accepted/In Press date: 18 August 2016
e-pub ahead of print date: 20 August 2016
Published date: October 2016
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 400521
URI: https://eprints.soton.ac.uk/id/eprint/400521
ISSN: 0891-5849
PURE UUID: 471c463c-ca08-492a-a509-a6a8a7a61730
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 19 Sep 2016 08:59
Last modified: 26 Nov 2019 06:33

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Contributors

Author: Anne-Roos S. Frenay
Author: Martin H. de Borst
Author: Matthias Bachtler
Author: Nadine Tschopp
Author: Charlotte A. Keyzer
Author: Else van den Berg
Author: Stephan J.L. Bakker
Author: Martin Feelisch ORCID iD
Author: Andreas Pasch
Author: Harry van Goor

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