Kidney Function-Dependence of Vitamin K-Status Parameters: Results from the TransplantLines Biobank and Cohort Studies

Daan Kremer; Dion Groothof; Charlotte A. Keyzer; Coby Eelderink; Tim J. Knobbe; Adrian Post; Marco van Londen; Michele F. Eisenga; TransplantLines Investigators; Leon J. Schurgers; Stefan P. Berger; Martin H. de Borst; Stephan J. L. Bakker

doi:10.3390/nu13093069

Nutrients (Aug 2021)

Kidney Function-Dependence of Vitamin K-Status Parameters: Results from the TransplantLines Biobank and Cohort Studies

Daan Kremer,
Dion Groothof,
Charlotte A. Keyzer,
Coby Eelderink,
Tim J. Knobbe,
Adrian Post,
Marco van Londen,
Michele F. Eisenga,
TransplantLines Investigators,
Leon J. Schurgers,
Stefan P. Berger,
Martin H. de Borst,
Stephan J. L. Bakker

Affiliations

Daan Kremer: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Dion Groothof: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Charlotte A. Keyzer: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Coby Eelderink: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Tim J. Knobbe: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Adrian Post: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Marco van Londen: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Michele F. Eisenga: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
TransplantLines Investigators: University Medical Center Groningen Transplant Center, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Leon J. Schurgers: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, 6200 MD Maastricht, The Netherlands
Stefan P. Berger: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Martin H. de Borst: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands
Stephan J. L. Bakker: Department of Internal Medicine, Division of Nephrology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands

DOI: https://doi.org/10.3390/nu13093069
Journal volume & issue: Vol. 13, no. 9
p. 3069

Abstract

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High circulating dephosphorylated (dp) uncarboxylated (uc) matrix Gla protein (MGP) and uc osteocalcin (OC) concentrations are regarded as markers of vitamin K-deficiency. However, because MGP and OC are small molecules, they may potentially pass the glomerulus, and their blood concentrations may strongly depend on kidney function. However, many studies with vitamin K-status parameters do not structurally adjust for baseline kidney function, and detailed studies on kidney function-dependence of vitamin K-status markers are lacking. We therefore measured plasma dp-ucMGP using a chemiluminescent assay in 578 kidney transplant recipients (41% females, age 56 ± 13y, 7.5 (3.2 to 13.7)y after transplantation, eGFR 49 ± 17 mL/min/1.73 m2) participating in the prospective TransplantLines Cohort Studies. Additionally, dp-carboxylated MGP, ucOC and carboxylated OC were measured using ELISA in plasma of a subgroup of 60 participants. Finally, dp-ucMGP was measured in a separate cohort of 124 kidney transplant recipients before and three months after kidney transplantation. Dp-ucMGP positively correlated with creatinine, cystatin C, and negatively with eGFR (Spearman’s ρ 0.54, 0.60, and −0.54, respectively, p 2 increase in eGFR was associated with a 14.0% lower dp-ucMGP. Additionally, dp-ucMGP strongly declined after kidney transplantation (pretransplantation: 1252 (868 to 1744) pmol/L to posttransplantation: 609 (451 to 914) pmol/L, p < 0.001). Proportions of dp-ucMGP over total MGP and ucOC over total OC were not associated with eGFR. This study highlights that dp-ucMGP is strongly associated with kidney function, and that levels strongly decrease after kidney transplantation. We therefore propose adequate adjustment for kidney function, or the use of kidney function-independent parameters such as proportion of uncarboxylated MGP or OC in the assessment of vitamin K-status in clinical practice and research.

Published in Nutrients

ISSN: 2072-6643 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology: Home economics: Nutrition. Foods and food supply
Website: https://www.mdpi.com/journal/nutrients

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