Urinary Excretion of <i>N</i>¹-Methylnicotinamide and <i>N</i>¹-Methyl-2-Pyridone-5-Carboxamide and Mortality in Kidney Transplant Recipients

• Main Authors: Carolien P.J. Deen, Anna van der Veen, António W. Gomes-Neto, Johanna M. Geleijnse, Karin J. Borgonjen-van den Berg, M. Rebecca Heiner-Fokkema, Ido P. Kema, Stephan J.L. Bakker
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Nutrients
• Subjects: <i>N</i>¹-methylnicotinamide; <i>N</i>¹-methyl-2-pyridone-5-carboxamide; urinary excretion; niacin status; renal transplantation; mortality
• Online Access: https://www.mdpi.com/2072-6643/12/7/2059

It is unclear whether niacin nutritional status is a target for improvement of long-term outcome after renal transplantation. The 24-h urinary excretion of <i>N</i>¹-methylnicotinamide (<i>N</i>¹-MN), as a biomarker of niacin status, has previously been shown to be negatively associated with premature mortality in kidney transplant recipients (KTR). However, recent evidence implies higher enzymatic conversion of <i>N</i>¹-MN to <i>N</i>¹-methyl-2-pyridone-5-carboxamide (2Py) in KTR, therefore the need exists for interpretation of both <i>N</i>¹-MN and 2Py excretion for niacin status assessment. We assessed niacin status by means of the 24-h urinary excretion of the sum of <i>N</i>¹-MN and 2Py (<i>N</i>¹-MN + 2Py), and its associations with risk of premature mortality in KTR. <i>N</i>¹-MN + 2Py excretion was measured in a longitudinal cohort of 660 KTR with LS-MS/MS. Prospective associations of <i>N</i>¹-MN + 2Py excretion were investigated with Cox regression analyses. Median <i>N</i>¹-MN + 2Py excretion was 198.3 (155.9–269.4) µmol/day. During follow-up of 5.4 (4.7–6.1) years, 143 KTR died, of whom 40 due to an infectious disease. <i>N</i>¹-MN + 2Py excretion was negatively associated with risk of all-cause mortality (HR 0.61; 95% CI 0.47–0.79; <i>p</i> < 0.001), and infectious mortality specifically (HR 0.47; 95% CI 0.29–0.75; <i>p</i> = 0.002), independent of potential confounders. Secondary analyses showed effect modification of hs-CRP on the negative prospective association of <i>N</i>¹-MN + 2Py excretion, and sensitivity analyses showed negative and independent associations of <i>N</i>¹-MN and 2Py excretion with risk of all-cause mortality separately. These findings add further evidence to niacin status as a target for nutritional strategies for improvement of long-term outcome in KTR.