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Plasma ADMA associates with all-cause mortality in renal transplant recipients

Plasma ADMA associates with all-cause mortality in renal transplant recipients
Plasma ADMA associates with all-cause mortality in renal transplant recipients
Asymmetric dimethylarginine (ADMA) is a key endogenous inhibitor of endothelial NO synthase that affects endothelial function, blood pressure and vascular remodeling. Increased plasma levels of ADMA are associated with worse outcome from cardiovascular disease. Due to endothelial dysfunction before and after kidney transplantation, renal transplant recipients (RTR) are at high risk for the alleged deleterious effects of ADMA. We investigated the associations of ADMA levels with all-cause mortality and graft failure in RTR. Plasma ADMA levels were determined in 686 stable outpatient RTR (57 % male, 53 ± 13 years), with a functioning graft for ?1 year. Determinants of ADMA were evaluated with multivariate linear regression models. Associations between ADMA and mortality were assessed using multivariable Cox regression analyses. The strongest associations with plasma ADMA in the multivariable analyses were male gender, donor age, parathyroid hormone, NT-pro-BNP and use of calcium supplements. During a median follow-up of 3.1 [2.7-3.9] years, 79 (12 %) patients died and 45 (7 %) patients developed graft failure. ADMA was associated with increased all-cause mortality [HR 1.52 (95 % CI 1.26-1.83] per SD increase, P < 0.001], whereby associations remained upon adjustment for confounders. ADMA was associated with graft failure [HR 1.41 (1.08-1.83) per SD increase, P = 0.01]; however, upon addition of eGFR significance was lost. High levels of plasma ADMA are associated with increased mortality in RTR. Our findings connect disturbed NO metabolism with patient survival after kidney transplantation.
0939-4451
1-9
Frenay, Anne-Roos S.
314506f7-a54f-4950-88fa-d22db328ab1d
van den Berg, Else
711eedae-261a-4ecf-86f4-295617ce1d95
de Borst, Martin H
6353763c-cd68-40ba-8b6d-516578574096
Beckmann, Bibiana
302f34f1-3ee6-4313-9fcc-daa73c069897
Tsikas, Dimitrios
396ecdca-73a0-4fc3-ac8b-e13daf17075d
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Navis, Gerjan
9f86f3c1-5e6e-49ab-97ff-261bb46a9900
Bakker, Stephan J L
48ec36f5-acbd-4cc3-82dd-3a8b7cb038f0
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3
Frenay, Anne-Roos S.
314506f7-a54f-4950-88fa-d22db328ab1d
van den Berg, Else
711eedae-261a-4ecf-86f4-295617ce1d95
de Borst, Martin H
6353763c-cd68-40ba-8b6d-516578574096
Beckmann, Bibiana
302f34f1-3ee6-4313-9fcc-daa73c069897
Tsikas, Dimitrios
396ecdca-73a0-4fc3-ac8b-e13daf17075d
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Navis, Gerjan
9f86f3c1-5e6e-49ab-97ff-261bb46a9900
Bakker, Stephan J L
48ec36f5-acbd-4cc3-82dd-3a8b7cb038f0
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3

Frenay, Anne-Roos S., van den Berg, Else, de Borst, Martin H, Beckmann, Bibiana, Tsikas, Dimitrios, Feelisch, Martin, Navis, Gerjan, Bakker, Stephan J L and van Goor, Harry (2015) Plasma ADMA associates with all-cause mortality in renal transplant recipients. Amino Acids, 1-9. (doi:10.1007/s00726-015-2023-0). (PMID:26077715)

Record type: Article

Abstract

Asymmetric dimethylarginine (ADMA) is a key endogenous inhibitor of endothelial NO synthase that affects endothelial function, blood pressure and vascular remodeling. Increased plasma levels of ADMA are associated with worse outcome from cardiovascular disease. Due to endothelial dysfunction before and after kidney transplantation, renal transplant recipients (RTR) are at high risk for the alleged deleterious effects of ADMA. We investigated the associations of ADMA levels with all-cause mortality and graft failure in RTR. Plasma ADMA levels were determined in 686 stable outpatient RTR (57 % male, 53 ± 13 years), with a functioning graft for ?1 year. Determinants of ADMA were evaluated with multivariate linear regression models. Associations between ADMA and mortality were assessed using multivariable Cox regression analyses. The strongest associations with plasma ADMA in the multivariable analyses were male gender, donor age, parathyroid hormone, NT-pro-BNP and use of calcium supplements. During a median follow-up of 3.1 [2.7-3.9] years, 79 (12 %) patients died and 45 (7 %) patients developed graft failure. ADMA was associated with increased all-cause mortality [HR 1.52 (95 % CI 1.26-1.83] per SD increase, P < 0.001], whereby associations remained upon adjustment for confounders. ADMA was associated with graft failure [HR 1.41 (1.08-1.83) per SD increase, P = 0.01]; however, upon addition of eGFR significance was lost. High levels of plasma ADMA are associated with increased mortality in RTR. Our findings connect disturbed NO metabolism with patient survival after kidney transplantation.

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Accepted/In Press date: 1 June 2015
Published date: 16 June 2015
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 378729
URI: https://eprints.soton.ac.uk/id/eprint/378729
ISSN: 0939-4451
PURE UUID: 3cf63443-9458-476d-bedb-017324dc3b20
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 09 Jul 2015 11:02
Last modified: 06 Jun 2018 12:29

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Contributors

Author: Anne-Roos S. Frenay
Author: Else van den Berg
Author: Martin H de Borst
Author: Bibiana Beckmann
Author: Dimitrios Tsikas
Author: Martin Feelisch ORCID iD
Author: Gerjan Navis
Author: Stephan J L Bakker
Author: Harry van Goor

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