Urinary Excretion of N1-Methylnicotinamide, as a Biomarker of Niacin Status, and Mortality in Renal Transplant Recipients

Carolien P J Deen; Anna van der Veen; Martijn van Faassen; Isidor Minović; António W Gomes-Neto; Johanna M Geleijnse; Karin J Borgonjen-van den Berg; Ido P Kema; Stephan J L Bakker

doi:10.3390/jcm8111948

Urinary Excretion of N¹-Methylnicotinamide, as a Biomarker of Niacin Status, and Mortality in Renal Transplant Recipients

J Clin Med. 2019 Nov 12;8(11):1948. doi: 10.3390/jcm8111948.

Authors

Affiliations

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 Food and Nutrition, 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.

Abstract

Renal transplant recipients (RTR) commonly suffer from vitamin B₆ deficiency and its functional consequences add to an association with poor long-term outcome. It is unknown whether niacin status is affected in RTR and, if so, whether this affects clinical outcomes, as vitamin B₆ is a cofactor in nicotinamide biosynthesis. We compared 24-h urinary excretion of N¹-methylnicotinamide (N¹-MN) as a biomarker of niacin status in RTR with that in healthy controls, in relation to dietary intake of tryptophan and niacin as well as vitamin B₆ status, and investigated whether niacin status is associated with the risk of premature all-cause mortality in RTR. In a prospective cohort of 660 stable RTR with a median follow-up of 5.4 (4.7-6.1) years and 275 healthy kidney donors, 24-h urinary excretion of N¹-MN was measured with liquid chromatography-tandem mass spectrometry LC-MS/MS. Dietary intake was assessed by food frequency questionnaires. Prospective associations of N¹-MN excretion with mortality were investigated by Cox regression analyses. Median N¹-MN excretion was 22.0 (15.8-31.8) μmol/day in RTR, compared to 41.1 (31.6-57.2) μmol/day in healthy kidney donors (p < 0.001). This difference was independent of dietary intake of tryptophan (1059 ± 271 and 1089 ± 308 mg/day; p = 0.19), niacin (17.9 ± 5.2 and 19.2 ± 6.2 mg/day; p < 0.001), plasma vitamin B₆ (29.0 (17.5-49.5), and 42.0 (29.8-60.3) nmol/L; p < 0.001), respectively. N¹-MN excretion was inversely associated with the risk of all-cause mortality in RTR (HR 0.57; 95% CI 0.45-0.71; p < 0.001), independent of potential confounders. RTR excrete less N¹-MN in 24-h urine than healthy controls, and our data suggest that this difference cannot be attributed to lower dietary intake of tryptophan and niacin, nor vitamin B₆ status. Importantly, lower 24-h urinary excretion of N¹-MN is independently associated with a higher risk of premature all-cause mortality in RTR.

Keywords: dietary intake; kidney transplantation; mortality; niacin status; tryptophan; urinary excretion of N1-methylnicotinamide; vitamin B3.

Abstract

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