Matrix Gla protein is an independent predictor of both intimal and medial vascular calcification in chronic kidney disease

Jaminon, Armand M. G.; Dai, Lu; Qureshi, Abdul Rashid; Evenepoel, Pieter; Ripsweden, Jonaz; Söderberg, Magnus; Witasp, Anna; Olauson, Hannes; Schurgers, Leon J.; Stenvinkel, Peter

doi:10.1038/s41598-020-63013-8

Cited by 55 publications

(40 citation statements)

References 38 publications

(37 reference statements)

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“…We used the inactive dp-ucMGP as a marker of vitamin K status and found similar results compared to these previous studies, which suggest that vitamin K may specifically be involved in medial calcification. These results are also in line with a recent study of Jaminon et al showing an association of high dp-ucMGP concentrations with high medial calcification scores in patients with chronic kidney disease [29]. However, further research is necessary to confirm these biomarkers as markers for IAC and MAC.…”

Section: Femoral Calcification Crural Calcificationsupporting

confidence: 91%

Intimal and medial calcification in relation to cardiovascular risk factors

et al. 2020

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To assess specific risk factors and biomarkers associated with intimal arterial calcification (IAC) and medial arterial calcification (MAC). Methods We conducted a cross-sectional study in patients with or at risk of vascular disease from the SMART study(n = 520) and the DCS cohort(n = 198). Non-contrast computed tomography scanning of the lower extremities was performed and calcification in the femoral and crural arteries was scored as absent, predominant IAC, predominant MAC or indistinguishable. Multinomial regression models were used to assess the associations between cardiovascular risk factors and calcification patterns. Biomarkers for inflammation, calcification and vitamin K status were measured in a subset of patients with IAC(n = 151) and MAC(n = 151). Results Femoral calcification was found in 77% of the participants, of whom 38% had IAC, 28% had MAC and 11% were scored as indistinguishable. The absolute agreement between the femoral and crural arteries was high(69%). Higher age, male sex, statin use and history of coronary artery disease were associated with higher prevalences of femoral IAC and MAC

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Section: Femoral Calcification Crural Calcificationsupporting

confidence: 91%

Intimal and medial calcification in relation to cardiovascular risk factors

et al. 2020

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“…Circulating dp-ucMGP levels were determined in EDTA plasma using the commercially available IVD CE marked chemiluminescent InaKif MGP assay on the IDS-iSYS system (IDS, Boldon, UK). 28 In brief, 50 μL of patient sample or calibrators were incubated with magnetic particles coated with murine monoclonal dpMGP antibody, an acridinium labelled murine monoclonal ucMGP antibody and assay buffer. The magnetic particles were captured using a magnet and a wash step performed to remove any unbound analyte.…”

Section: Quantification Of Dp-ucmgpmentioning

confidence: 99%

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Dofferhoff¹,

Piscaer²,

Schurgers³

et al. 2020

Preprint

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Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P<0.001), thoracic aortic calcification (P<0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

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“…The MGP is generally accepted to be responsible for the protective effects of CaSR [ 53 ]. MGP is one of the most important inhibitors against vascular calcification [ 54 ] and is a vitamin K-dependent protein that is mainly synthesized by VSMCs and chondrocytes. MGP-knockout mice were found to die in two months owing to extensive arterial calcification and aortic rupture [ 55 ].…”

Section: Ca 2+ Signaling In Vascular Calcificatmentioning

confidence: 99%

Crosstalk between Renal and Vascular Calcium Signaling: The Link between Nephrolithiasis and Vascular Calcification

Liu

Cheng

Tsai

et al. 2021

IJMS

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Calcium (Ca2+) is an important mediator of multicellular homeostasis and is involved in several diseases. The interplay among the kidney, bone, intestine, and parathyroid gland in Ca2+ homeostasis is strictly modulated by numerous hormones and signaling pathways. The calcium-sensing receptor (CaSR) is a G protein–coupled receptor, that is expressed in calcitropic tissues such as the parathyroid gland and the kidney, plays a pivotal role in Ca2+ regulation. CaSR is important for renal Ca2+, as a mutation in this receptor leads to hypercalciuria and calcium nephrolithiasis. In addition, CaSR is also widely expressed in the vascular system, including vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) and participates in the process of vascular calcification. Aberrant Ca2+ sensing by the kidney and VSMCs, owing to altered CaSR expression or function, is associated with the formation of nephrolithiasis and vascular calcification. Based on emerging epidemiological evidence, patients with nephrolithiasis have a higher risk of vascular calcification, but the exact mechanism linking the two conditions is unclear. However, a dysregulation in Ca2+ homeostasis and dysfunction in CaSR might be the connection between the two. This review summarizes renal calcium handling and calcium signaling in the vascular system, with a special focus on the link between nephrolithiasis and vascular calcification.

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Matrix Gla protein is an independent predictor of both intimal and medial vascular calcification in chronic kidney disease

Cited by 55 publications

References 38 publications

Intimal and medial calcification in relation to cardiovascular risk factors

Intimal and medial calcification in relation to cardiovascular risk factors

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Crosstalk between Renal and Vascular Calcium Signaling: The Link between Nephrolithiasis and Vascular Calcification

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