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

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

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number2059
Pages (from-to)1-18
Number of pages17
JournalNutrients
Volume12
Issue number7
DOIs
Publication statusPublished - 10-Jul-2020

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