TY - JOUR
T1 - Functional vitamin B-6 status and long-term mortality in renal transplant recipients
AU - Minović, Isidor
AU - van der Veen, Anna
AU - van Faassen, Martijn
AU - Riphagen, Ineke J.
AU - van den Berg, Else
AU - van der Ley, Claude
AU - Gomes-Neto, António W.
AU - Geleijnse, Johanna M.
AU - Eggersdorfer, Manfred
AU - Navis, Gerjan J.
AU - Kema, Ido P.
AU - Bakker, Stephan J. L.
N1 - © 2017 American Society for Nutrition.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Background: Low plasma concentrations of pyridoxal 5'-phosphate (PLP) are common in renal transplant recipients (RTRs) and confer increased risk of long-term mortality. To our knowledge, it is not known whether low plasma PLP concentrations have functional (i.e., intracellular) consequences and, if so, whether such consequences are associated with increased risk of mortality.Objectives: We assessed the association of plasma PLP with functional vitamin B-6 status and explored the potential association of functional vitamin B-6 status with long-term mortality in RTRs.Design: In a longitudinal cohort of 678 stable RTRs with a median follow-up of 5.3 y (IQR: 4.8-6.1 y) and 297 healthy controls, PLP, plasma 3-hydroxykynurenine (3-HK), and xanthurenic acid (XA) were analyzed via validated assays. PLP was used as direct biomarker for vitamin B-6 status, and the 3-HK: XA ratio was used as functional biomarker of vitamin B-6 status with a higher ratio reflecting worse functional vitamin B-6 status.Results: Median PLP, 3-HK, and XA concentrations were 41 nmol/L (IQR: 29-60 nmol/L), 40.1 nmol/L (IQR: 33.0-48.0 nmol/L), and 19.1 nmol/L (IQR: 14.5-24.9 nmol/L), respectively, in healthy controls compared with 29 nmol/L (IQR: 17-50 nmol/L), 61.5 nmol/L (IQR: 45.6-86.5 nmol/L), and 25.5 nmol/L (IQR: 17.2-40.0 nmol/L), respectively, in RTRs (all P <0.001). RTRs had a higher median 3-HK: XA ratio (2.38; IQR: 1.68-3.49) than did healthy controls (2.13; IQR: 1.63-2.71) (P <0.05). In RTRs, the 3-HK: XA ratio was inversely associated with plasma PLP (beta = -20.21, P <0.001). Moreover, a higher 3-HK: XA ratio was independently associated with increased risk of all-cause mortality (HR per SD increment: 1.30; 95% CI: 1.13, 1.49), cancer mortality (HR per SD increment: 1.47; 95% CI: 1.12, 1.95), and infectious disease mortality (HR per SD increment: 1.50; 95% CI: 1.21, 1.86) in RTRs.Conclusions: Vitamin B-6-deficient RTRs have a worse functional vitamin B-6 status than do healthy controls and vitamin B-6-sufficient RTRs. Worse functional vitamin B-6 status in RTRs is independently associated with an increased risk of mortality particularly because of cancer and infectious disease.
AB - Background: Low plasma concentrations of pyridoxal 5'-phosphate (PLP) are common in renal transplant recipients (RTRs) and confer increased risk of long-term mortality. To our knowledge, it is not known whether low plasma PLP concentrations have functional (i.e., intracellular) consequences and, if so, whether such consequences are associated with increased risk of mortality.Objectives: We assessed the association of plasma PLP with functional vitamin B-6 status and explored the potential association of functional vitamin B-6 status with long-term mortality in RTRs.Design: In a longitudinal cohort of 678 stable RTRs with a median follow-up of 5.3 y (IQR: 4.8-6.1 y) and 297 healthy controls, PLP, plasma 3-hydroxykynurenine (3-HK), and xanthurenic acid (XA) were analyzed via validated assays. PLP was used as direct biomarker for vitamin B-6 status, and the 3-HK: XA ratio was used as functional biomarker of vitamin B-6 status with a higher ratio reflecting worse functional vitamin B-6 status.Results: Median PLP, 3-HK, and XA concentrations were 41 nmol/L (IQR: 29-60 nmol/L), 40.1 nmol/L (IQR: 33.0-48.0 nmol/L), and 19.1 nmol/L (IQR: 14.5-24.9 nmol/L), respectively, in healthy controls compared with 29 nmol/L (IQR: 17-50 nmol/L), 61.5 nmol/L (IQR: 45.6-86.5 nmol/L), and 25.5 nmol/L (IQR: 17.2-40.0 nmol/L), respectively, in RTRs (all P <0.001). RTRs had a higher median 3-HK: XA ratio (2.38; IQR: 1.68-3.49) than did healthy controls (2.13; IQR: 1.63-2.71) (P <0.05). In RTRs, the 3-HK: XA ratio was inversely associated with plasma PLP (beta = -20.21, P <0.001). Moreover, a higher 3-HK: XA ratio was independently associated with increased risk of all-cause mortality (HR per SD increment: 1.30; 95% CI: 1.13, 1.49), cancer mortality (HR per SD increment: 1.47; 95% CI: 1.12, 1.95), and infectious disease mortality (HR per SD increment: 1.50; 95% CI: 1.21, 1.86) in RTRs.Conclusions: Vitamin B-6-deficient RTRs have a worse functional vitamin B-6 status than do healthy controls and vitamin B-6-sufficient RTRs. Worse functional vitamin B-6 status in RTRs is independently associated with an increased risk of mortality particularly because of cancer and infectious disease.
KW - cancer
KW - functional vitamin B-6 status
KW - infectious disease
KW - long-term mortality
KW - renal transplantation
KW - MULTIPLE IMPUTATION
KW - MASS-SPECTROMETRY
KW - PLASMA
KW - DEFICIENCY
KW - KYNURENINE
KW - SERUM
KW - RISK
U2 - 10.3945/ajcn.117.164012
DO - 10.3945/ajcn.117.164012
M3 - Article
C2 - 28978540
SN - 0002-9165
VL - 106
SP - 1366
EP - 1374
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 6
ER -