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Open AccessArticle

Urinary Excretion of N1-Methylnicotinamide and N1-Methyl-2-Pyridone-5-Carboxamide and Mortality in Kidney Transplant Recipients

1
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
2
Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
3
Top Institute of Food and Nutrition (TIFN), 6709 PA Wageningen, The Netherlands
4
TransplantLines Food and Nutrition Biobank and Cohort Study, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
5
Division of Human Nutrition and Health, Wageningen University, 6708 PB Wageningen, The Netherlands
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(7), 2059; https://doi.org/10.3390/nu12072059
Received: 26 May 2020 / Revised: 4 July 2020 / Accepted: 8 July 2020 / Published: 10 July 2020
(This article belongs to the Special Issue Renal Nutrition and Metabolism)
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 N1-methylnicotinamide (N1-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 N1-MN to N1-methyl-2-pyridone-5-carboxamide (2Py) in KTR, therefore the need exists for interpretation of both N1-MN and 2Py excretion for niacin status assessment. We assessed niacin status by means of the 24-h urinary excretion of the sum of N1-MN and 2Py (N1-MN + 2Py), and its associations with risk of premature mortality in KTR. N1-MN + 2Py excretion was measured in a longitudinal cohort of 660 KTR with LS-MS/MS. Prospective associations of N1-MN + 2Py excretion were investigated with Cox regression analyses. Median N1-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. N1-MN + 2Py excretion was negatively associated with risk of all-cause mortality (HR 0.61; 95% CI 0.47–0.79; p < 0.001), and infectious mortality specifically (HR 0.47; 95% CI 0.29–0.75; p = 0.002), independent of potential confounders. Secondary analyses showed effect modification of hs-CRP on the negative prospective association of N1-MN + 2Py excretion, and sensitivity analyses showed negative and independent associations of N1-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. View Full-Text
Keywords: N1-methylnicotinamide; N1-methyl-2-pyridone-5-carboxamide; urinary excretion; niacin status; renal transplantation; mortality; vitamin B3; tryptophan; dietary intake N1-methylnicotinamide; N1-methyl-2-pyridone-5-carboxamide; urinary excretion; niacin status; renal transplantation; mortality; vitamin B3; tryptophan; dietary intake
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Deen, C.P.; Veen, A.; Gomes-Neto, A.W.; Geleijnse, J.M.; Berg, K. .-V.; Heiner-Fokkema, M.R.; Kema, I.P.; Bakker, S.J. Urinary Excretion of N1-Methylnicotinamide and N1-Methyl-2-Pyridone-5-Carboxamide and Mortality in Kidney Transplant Recipients. Nutrients 2020, 12, 2059.

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