Nitric oxide and long-term outcomes after kidney transplantation: results of the TransplantLines cohort study
Nitric oxide and long-term outcomes after kidney transplantation: results of the TransplantLines cohort study
Impaired endogenous nitric oxide (NO) production may contribute to graft failure and premature mortality in kidney transplant recipients (KTR). We investigated potential associations of 24-h urinary NOx (NO3- + NO2-) excretion (uNOx) with long-term outcomes. uNOx was determined by HPLC and GC-MS in 698 KTR and in 132 kidney donors before and after donation. Additionally, we measured urinary nitroso species (RXNO) by gas-phase chemiluminescence. Median uNOx was lower in KTR compared to kidney donors (688 [393-1076] vs. 1301 [868-1863] before donation and 1312 [982-1853] μmol/24h after donation, P < 0.001). During median follow-up of 5.4 [4.8-6.1] years, 150 KTR died (61 due to cardiovascular disease) and 83 experienced graft failure. uNOx was inversely associated with all-cause mortality (HR per doubling of uNOx: 0.84 [95% CI 0.75-0.93], P < 0.001) and cardiovascular mortality (HR 0.78 [95% CI 0.67-0.92], P = 0.002). The association of uNOx with graft failure was lost when adjusted for renal function (HR per doubling of uNOx: 0.89 [95% CI 0.76-1.05], P = 0.17). There were no significant associations of urinary RXNO with outcomes. Our study suggests that KTR have lower NO production than healthy subjects and that lower uNOx is associated with a higher risk of all-cause and cardiovascular mortality.
Kidney transplant recipients, Kidney transplantation, Nitric oxide, Outcome
1-11
Maassen, Hanno
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Said, M Yusof
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Frenay, Anne-Roos S
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Koning, Anne
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Post, Adrian
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Riphagen, Ineke J
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Heiner-Fokkema, M Rebecca
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Drabert, Kathrin
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Fernandez, Bernadette O
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Gans, Reinold O B
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van den Berg, Else
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Navis, Gerjan
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Tsikas, Dimitrios
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Feelisch, Martin
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Bakker, Stephan J L
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van Goor, Harry
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1 August 2022
Maassen, Hanno
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Said, M Yusof
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Frenay, Anne-Roos S
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Koning, Anne
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Post, Adrian
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Riphagen, Ineke J
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Heiner-Fokkema, M Rebecca
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Drabert, Kathrin
76c9412f-33fa-42ff-8a07-32372e3a2386
Fernandez, Bernadette O
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Gans, Reinold O B
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van den Berg, Else
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Navis, Gerjan
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Tsikas, Dimitrios
396ecdca-73a0-4fc3-ac8b-e13daf17075d
Feelisch, Martin
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Bakker, Stephan J L
48ec36f5-acbd-4cc3-82dd-3a8b7cb038f0
van Goor, Harry
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Maassen, Hanno, Said, M Yusof, Frenay, Anne-Roos S, Koning, Anne, Post, Adrian, Riphagen, Ineke J, Heiner-Fokkema, M Rebecca, Drabert, Kathrin, Fernandez, Bernadette O, Gans, Reinold O B, van den Berg, Else, Navis, Gerjan, Tsikas, Dimitrios, Feelisch, Martin, Bakker, Stephan J L and van Goor, Harry
(2022)
Nitric oxide and long-term outcomes after kidney transplantation: results of the TransplantLines cohort study.
Nitric Oxide, 125-126, .
(doi:10.1016/j.niox.2022.05.005).
Abstract
Impaired endogenous nitric oxide (NO) production may contribute to graft failure and premature mortality in kidney transplant recipients (KTR). We investigated potential associations of 24-h urinary NOx (NO3- + NO2-) excretion (uNOx) with long-term outcomes. uNOx was determined by HPLC and GC-MS in 698 KTR and in 132 kidney donors before and after donation. Additionally, we measured urinary nitroso species (RXNO) by gas-phase chemiluminescence. Median uNOx was lower in KTR compared to kidney donors (688 [393-1076] vs. 1301 [868-1863] before donation and 1312 [982-1853] μmol/24h after donation, P < 0.001). During median follow-up of 5.4 [4.8-6.1] years, 150 KTR died (61 due to cardiovascular disease) and 83 experienced graft failure. uNOx was inversely associated with all-cause mortality (HR per doubling of uNOx: 0.84 [95% CI 0.75-0.93], P < 0.001) and cardiovascular mortality (HR 0.78 [95% CI 0.67-0.92], P = 0.002). The association of uNOx with graft failure was lost when adjusted for renal function (HR per doubling of uNOx: 0.89 [95% CI 0.76-1.05], P = 0.17). There were no significant associations of urinary RXNO with outcomes. Our study suggests that KTR have lower NO production than healthy subjects and that lower uNOx is associated with a higher risk of all-cause and cardiovascular mortality.
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Accepted/In Press date: 31 May 2022
e-pub ahead of print date: 2 June 2022
Published date: 1 August 2022
Additional Information:
Funding Information:
The authors would like to express their gratitude towards Magdalena Minnion for her expertise and valuable help in measuring urinary NOx. This work was supported by Grants from the Dutch Kidney Foundation [ NSN C08-2254 , P13-114 , 14OKK28 ] www.gasotransmitters.eu . MF gratefully acknowledges support from the UK Medical Research Council [ G1001536 ].
Funding Information:
The authors would like to express their gratitude towards Magdalena Minnion for her expertise and valuable help in measuring urinary NOx. This work was supported by Grants from the Dutch Kidney Foundation [NSN C08-2254, P13-114, 14OKK28] www.gasotransmitters.eu. MF gratefully acknowledges support from the UK Medical Research Council [G1001536].
Publisher Copyright:
© 2022
Keywords:
Kidney transplant recipients, Kidney transplantation, Nitric oxide, Outcome
Identifiers
Local EPrints ID: 458098
URI: http://eprints.soton.ac.uk/id/eprint/458098
ISSN: 1089-8603
PURE UUID: ced7483d-ba39-46c7-8a63-e5772247639a
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Date deposited: 28 Jun 2022 16:59
Last modified: 17 Mar 2024 03:31
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Contributors
Author:
Hanno Maassen
Author:
M Yusof Said
Author:
Anne-Roos S Frenay
Author:
Anne Koning
Author:
Adrian Post
Author:
Ineke J Riphagen
Author:
M Rebecca Heiner-Fokkema
Author:
Kathrin Drabert
Author:
Bernadette O Fernandez
Author:
Reinold O B Gans
Author:
Else van den Berg
Author:
Gerjan Navis
Author:
Dimitrios Tsikas
Author:
Stephan J L Bakker
Author:
Harry van Goor
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