Nitric oxide and long-term outcomes after kidney transplantation: Results of the TransplantLines cohort study

Hanno Maassen, M. Yusof Said, Anne-Roos S. Frenay, Anne Koning, Adrian Post, Ineke J. Riphagen, M. Rebecca Heiner-Fokkema, Kathrin Drabert, Bernadette O. Fernandez, Reinold O. B. Gans, Else van den Berg, Gerjan Navis, Dimitrios Tsikas, Martin Feelisch, Stephan J. L. Bakker, Harry van Goor

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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/24 h 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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalNitric oxide
Publication statusPublished - 1 Aug 2022


  • Kidney transplant recipients
  • Kidney transplantation
  • Nitric oxide
  • Outcome

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