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

摘要

Renal transplant recipients (RTR) commonly suffer from vitamin B 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 B is a cofactor in nicotinamide biosynthesis. We compared 24-h urinary excretion of -methylnicotinamide ( -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 B 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 -MN was measured with liquid chromatography-tandem mass spectrometry LC-MS/MS. Dietary intake was assessed by food frequency questionnaires. Prospective associations of -MN excretion with mortality were investigated by Cox regression analyses. Median -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 ( < 0.001). This difference was independent of dietary intake of tryptophan (1059 ± 271 and 1089 ± 308 mg/day; = 0.19), niacin (17.9 ± 5.2 and 19.2 ± 6.2 mg/day; < 0.001), plasma vitamin B (29.0 (17.5–49.5), and 42.0 (29.8–60.3) nmol/L; < 0.001), respectively. -MN excretion was inversely associated with the risk of all-cause mortality in RTR (HR 0.57; 95% CI 0.45–0.71; < 0.001), independent of potential confounders. RTR excrete less -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 B status. Importantly, lower 24-h urinary excretion of -MN is independently associated with a higher risk of premature all-cause mortality in RTR.