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.
Highlights
Kidney transplantation is the preferred treatment for end-stage renal disease in terms of survival, quality of life and costs [1,2]
Intake of tryptophan was similar in both groups (1059 ± 271 and 1089 ± 308 mg/day, respectively; p = 0.19), while intake of niacin was lower in renal transplant recipients (RTR) than in kidney donors (17.9 ± 5.2 and 19.2 ± 6.2 mg/day, respectively; p = 0.01)
In this large prospective cohort study, we showed that 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
Summary
Kidney transplantation is the preferred treatment for end-stage renal disease in terms of survival, quality of life and costs [1,2]. While short-term patient outcomes are continuing to improve, the long-term posttransplant survival has remained largely unchanged over the past few decades [4]. Improving perspectives relies on the management of modifiable factors that impact long-term outcome in RTR, of which nutrition is increasingly acknowledged [6,7]. We found that RTR commonly suffer from vitamin B6 deficiency and its functional consequences that add to an association with poor long-term outcomes [8]. As vitamin B6 is an essential cofactor of key enzymes involved in de novo biosynthesis of nicotinamide from tryptophan [9], niacin deficiency might be lurking in these patients as well. Nicotinamide, nicotinic acid, and nicotinamide riboside are collectively referred to as niacin or vitamin B3, and are precursors of the metabolically active NAD+. NAD+ is catabolized to N1-methylnicotinamide (N1-MN) through methylation of nicotinamide in the liver, and the 24-h urinary excretion of N1-MN is considered the most reliable biomarker of niacin status [12,13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
