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

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.