Vitamin K2 supplementation and arterial stiffness among renal transplant recipients—a single-arm, single-center clinical trial

Mansour, Anthony G.; Hariri, Essa; Daaboul, Yazan; Korjian, Serge; Alam, Andrew El; Protogerou, Athanase D.; Kilany, H; Karam, A; Stephan, A; Bahous, Sola Aoun

doi:10.1016/j.jash.2017.07.001

Cited by 55 publications

(54 citation statements)

References 41 publications

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“…Circulating concentrations of dephosphorylated‐uncarboxylated (inactive) MGP (dp‐ucMGP) have been shown to reflect vitamin K2 status, and they were associated with the extent of vascular calcification, arterial stiffness, and development of CV events in specific populations . Interestingly, vitamin K2 deficiency is a modifiable risk factor, whereby supplementation of vitamin K2 has previously been demonstrated to result in a dose‐dependent reduction in dp‐ucMGP levels and improved arterial stiffness when studied among healthy adults, patients with end‐stage renal disease on hemodialysis, and renal transplant recipients …”

Section: Introductionmentioning

confidence: 99%

Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case‐Control Study

et al. 2019

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Objective We aimed to examine arterial stiffness and vitamin K2 status in migraine subjects by comparison to controls. Background Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but vitamin K2 status has never been explored in migraine subjects. Design and Methods This is a case‐control, single‐center, observational study that includes a cohort of subjects with migraine and their age‐ and sex‐matched controls. Arterial stiffness was measured using carotid‐femoral pulse wave velocity (cfPWV). Dephosphorylated‐uncarboxylated matrix‐Gla‐protein (dp‐ucMGP) was used as a marker for vitamin K2 status. A propensity‐matched scoring method was used. Results A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P < .001), as well as higher dp‐ucMGP (454.3 ± 116.7 pmol/L vs 379.8 ± 126.6 pmol/L, 95% CI of mean difference [34.63, 114.31], P < .001). Higher cfPWV was associated with higher dp‐ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of vitamin K2 deficiency (dp‐ucMGP ≥ 500 pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P = .193). Conclusions Individuals with migraine have worse indices of arterial stiffness as compared with their age‐ and sex‐matched control subjects. This increase in arterial stiffness is associated with an increase in markers of vitamin K2 deficiency in the MWA group.

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Section: Introductionmentioning

confidence: 99%

Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case‐Control Study

et al. 2019

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“…Some evidence revealed a significant reverse relation between dp-ucMGP and kidney function (9,13,21,34). Results of a cohort study showed that kidney transplant recipients at the highest quartile of dp-ucMGP had a higher risk of developing transplant failure and mortality risk (13).…”

Section: Discussionmentioning

confidence: 99%

“…It seems that micro-vascular dysregulation of kidney such as micro-albuminuria is inversely related to the circulating level of vitamin K and activated MGP levels (19). There is some evidence that serum level of dp-ucMGP is directly related to proteinuria and serum creatinine and inversely related to renal function (GFR, glomerular filtration rate) in patients with CKD (20)(21)(22)(23)(24)(25)(26).…”

Section: Article Typementioning

confidence: 99%

The association of serum dephosphorylated-uncarboxylated matrix gamma carboxyglutamate protein (dp-ucMGP) as a marker of vascular vitamin K status with allograft function in kidney transplant recipients

et al. 2019

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Implication for health policy/practice/research/medical education:In a study on 90 kidney transplant recipients in the post-transplant phase, we found, the mean serum level of dephosphorylateduncarboxylated matrix gamma carboxyglutamate protein (dp-ucMGP) was in normal range. However, a small percentage of participants had high serum dp-ucMGP (>12 µg/L). Serum dp-ucMGP did not have any statistical significant association with serum urea, creatinine and kidney function, since previous studies showed high serum level of dp-ucMGP may make kidney transplant recipients susceptible to the cardiovascular events and transplant rejection. Please cite this paper as: Ebrahimzadeh Attari V, Shahvegharasl Z, Fathalizadeh P, Pourasghary S, Mohajel Shoja M, Niknafs B, Ardalan M. The association of serum dephosphorylated-uncarboxylated matrix gamma carboxyglutamate protein (dp-ucMGP) as a marker of vascular vitamin K status with allograft function in kidney transplant recipients. J Nephropathol. 2020;9(3):e24.

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“…In the study by Kurnatowska et al, it was shown that daily intake of 90 µg of MK-7 resulted in a slower progression of VC in a cohort of 42 CKD patients (66). Large daily dose of 360 µg of MK-7 for 2 months was accompanied by a 14.2% reduction of arterial stiffness in a cohort of 60 kidney transplant recipients (68). Lees et al (69), conducted a meta-analysis including 13 controlled clinical studies and 14 longitudinal trials in 12,888 patients and found that compared to control, vitamin K supplementation was associated with a 9.1% reduction in VC status, accompanied by a 44.7% decrease in dp-ucMGP levels.…”

Section: Vitamin K: the Essential Co-factor Of Mgpmentioning

confidence: 97%

Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein

et al. 2020

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Arterial calcification is highly prevalent in chronic kidney disease (CKD) patients and is associated with cardiovascular (CV) morbidity and mortality. Patients at early CKD stages are more likely to suffer a fatal CV event than to develop end-stage renal disease and require hemodialysis treatment. The heavy CV burden of these patients cannot be solely explained by traditional calcification risk factors. Moreover, the pathophysiologic mechanisms underlying this association are complex and yet not fully understood. Although vascular calcification was regarded as a passive degenerative process for over a century, this theory changed by recent evidence that pointed toward an active process, where calcification promoters and inhibitors were involved. Matrix Gla Protein (MGP) has been established as a strong inhibitor of calcification both in vitro and in vivo. Not only it prevents mineralization of the arterial wall, but it is the only factor that can actually reverse it. To become fully active, MGP must undergo carboxylation of specific protein bound glutamate residues, a process fully dependent on the availability of vitamin K. Low vitamin K status leads to inactive, uncarboxylated forms of MGP and has been repeatedly associated with accelerated vascular calcification. Aim of this review is to present the pathophysiologic mechanisms underlying the activation and function of MGP and review the existing, accumulating data regarding the association between vitamin K, MGP and vascular calcification/CV disease in CKD patients.

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Vitamin K2 supplementation and arterial stiffness among renal transplant recipients—a single-arm, single-center clinical trial

Cited by 55 publications

References 41 publications

Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case‐Control Study

Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case‐Control Study

The association of serum dephosphorylated-uncarboxylated matrix gamma carboxyglutamate protein (dp-ucMGP) as a marker of vascular vitamin K status with allograft function in kidney transplant recipients

Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein

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