Functional vitamin B-6 status and long-term mortality in renal transplant recipients

Isidor Minović, Anna van der Veen, Martijn van Faassen, Ineke J. Riphagen, Else van den Berg, Claude van der Ley, António W. Gomes-Neto, Johanna M. Geleijnse, Manfred Eggersdorfer, Gerjan J. Navis, Ido P. Kema, Stephan J.L. Bakker

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Abstract

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 (β = -0.21, 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. This trial was registered at clinicaltrials.gov as NCT02811835.

Original languageEnglish
Pages (from-to)1366-1374
JournalThe American journal of clinical nutrition
Volume106
Issue number6
DOIs
Publication statusPublished - 1 Dec 2017

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Vitamin B 6
Pyridoxal Phosphate
Kidney
Mortality
Communicable Diseases
Biomarkers
Transplant Recipients
3-hydroxykynurenine
xanthurenic acid
Neoplasms

Keywords

  • cancer
  • functional vitamin B-6 status
  • infectious disease
  • long-term mortality
  • renal transplantation

Cite this

Minović, I., van der Veen, A., van Faassen, M., Riphagen, I. J., van den Berg, E., van der Ley, C., ... Bakker, S. J. L. (2017). Functional vitamin B-6 status and long-term mortality in renal transplant recipients. The American journal of clinical nutrition, 106(6), 1366-1374. https://doi.org/10.3945/ajcn.117.164012
Minović, Isidor ; van der Veen, Anna ; van Faassen, Martijn ; Riphagen, Ineke J. ; van den Berg, Else ; van der Ley, Claude ; Gomes-Neto, António W. ; Geleijnse, Johanna M. ; Eggersdorfer, Manfred ; Navis, Gerjan J. ; Kema, Ido P. ; Bakker, Stephan J.L. / Functional vitamin B-6 status and long-term mortality in renal transplant recipients. In: The American journal of clinical nutrition. 2017 ; Vol. 106, No. 6. pp. 1366-1374.
@article{046a3fb2a8ed426dae09539580ec0299,
title = "Functional vitamin B-6 status and long-term mortality in renal transplant recipients",
abstract = "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 (β = -0.21, 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. This trial was registered at clinicaltrials.gov as NCT02811835.",
keywords = "cancer, functional vitamin B-6 status, infectious disease, long-term mortality, renal transplantation",
author = "Isidor Minović and {van der Veen}, Anna and {van Faassen}, Martijn and Riphagen, {Ineke J.} and {van den Berg}, Else and {van der Ley}, Claude and Gomes-Neto, {Ant{\'o}nio W.} and Geleijnse, {Johanna M.} and Manfred Eggersdorfer and Navis, {Gerjan J.} and Kema, {Ido P.} and Bakker, {Stephan J.L.}",
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Minović, I, van der Veen, A, van Faassen, M, Riphagen, IJ, van den Berg, E, van der Ley, C, Gomes-Neto, AW, Geleijnse, JM, Eggersdorfer, M, Navis, GJ, Kema, IP & Bakker, SJL 2017, 'Functional vitamin B-6 status and long-term mortality in renal transplant recipients' The American journal of clinical nutrition, vol. 106, no. 6, pp. 1366-1374. https://doi.org/10.3945/ajcn.117.164012

Functional vitamin B-6 status and long-term mortality in renal transplant recipients. / Minović, Isidor; van der Veen, Anna; van Faassen, Martijn; Riphagen, Ineke J.; van den Berg, Else; van der Ley, Claude; Gomes-Neto, António W.; Geleijnse, Johanna M.; Eggersdorfer, Manfred; Navis, Gerjan J.; Kema, Ido P.; Bakker, Stephan J.L.

In: The American journal of clinical nutrition, Vol. 106, No. 6, 01.12.2017, p. 1366-1374.

Research output: Contribution to journalArticleAcademicpeer-review

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.

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 (β = -0.21, 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. This trial was registered at clinicaltrials.gov as NCT02811835.

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 (β = -0.21, 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. This trial was registered at clinicaltrials.gov as NCT02811835.

KW - cancer

KW - functional vitamin B-6 status

KW - infectious disease

KW - long-term mortality

KW - renal transplantation

U2 - 10.3945/ajcn.117.164012

DO - 10.3945/ajcn.117.164012

M3 - Article

VL - 106

SP - 1366

EP - 1374

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 6

ER -

Minović I, van der Veen A, van Faassen M, Riphagen IJ, van den Berg E, van der Ley C et al. Functional vitamin B-6 status and long-term mortality in renal transplant recipients. The American journal of clinical nutrition. 2017 Dec 1;106(6):1366-1374. https://doi.org/10.3945/ajcn.117.164012