TY - JOUR
T1 - Kidney Function-Dependence of Vitamin K-Status Parameters
T2 - Results from the TransplantLines Biobank and Cohort Studies
AU - TransplantLines Investigators
AU - Kremer, Daan
AU - Groothof, Dion
AU - Keyzer, Charlotte A.
AU - Eelderink, Coby
AU - Knobbe, Tim J.
AU - Post, Adrian
AU - van Londen, Marco
AU - Eisenga, Michele F.
AU - Schurgers, Leon J.
AU - Berger, Stefan P.
AU - de Borst, Martin H.
AU - Bakker, Stephan J. L.
PY - 2021/9
Y1 - 2021/9
N2 - 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 m(2)) 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 rho 0.54, 0.60, and -0.54, respectively, p < 0.001 for all), and each 10 mL/min/1.73 m(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.
AB - 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 m(2)) 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 rho 0.54, 0.60, and -0.54, respectively, p < 0.001 for all), and each 10 mL/min/1.73 m(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.
KW - matrix Gla protein
KW - osteocalcin
KW - vitamin K
KW - vascular calcification
KW - kidney transplant
KW - kidney function
KW - MATRIX GLA-PROTEIN
KW - CYSTATIN-C
KW - VASCULAR CALCIFICATION
KW - RENAL-FUNCTION
KW - OSTEOCALCIN
KW - MARKER
U2 - 10.3390/nu13093069
DO - 10.3390/nu13093069
M3 - Article
C2 - 34578950
VL - 13
JO - Nutrients
JF - Nutrients
SN - 2072-6643
IS - 9
M1 - 3069
ER -