Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK)

Haroon, Sabrina; Davenport, Andrew; Ling, Lieng H.; Tai, Bee–Choo; Teo, Lynette-Li-San; Schurgers, Leon J.; Shroff, Rukshana; Fischer, Dagmar‐Christiane; Khatri, Priyanka; Low, Sanmay; Tan, Jia-Neng; Chua, Horng-Ruey; Teo, Boon-Wee; Ong, C. L.; Subramanian, Srinivas; Yeo, Xi-Er; Wong, Weng Fai; Lau, Titus

doi:10.1016/j.ekir.2023.06.011

Cited by 5 publications

(4 citation statements)

References 58 publications

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“…Furthermore, dp-ucMGP is a widely accepted surrogate biomarker of vitamin K adequacy, and studies have showed that oral vitamin K supplementation increases carboxylation of MGP and lowers plasma dp-ucMGP (14,23). Whereas the high dp-ucMGP levels are strongly suggestive for vascular vitamin K insu ciency to a level that the calci cation-inhibitory activity of MGP is impaired, which may contribute to the extremely high risk for arterial calci cation in hemodialysis patients (13,25). Besides, dp-ucMGP was also identi ed as a survival marker, with lower levels heralding a better prognosis and decreased vascular calci cation in previous studies (11,19,26).…”

Section: Discussionmentioning

confidence: 99%

“…Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) represents the completely non-functional nonphosphorylated and uncarboxylated form of MGP, which is set free into the circulation because of the low a nity for calcium and matrix vesicles (11,12). It has been reported that vitamin K de ciency is associated with the increased circulating dp-ucMGP in CKD patients (13,14). Moreover, dp-ucMGP has been repeatedly and strongly correlated with various indicators of vascular calci cation both in general population and cohorts with diabetes, atherosclerotic disease, heart failure, and CKD (11,(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

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Correlation between circulating dephosphorylated uncarboxylated matrix Gla protein and vascular calcification in peritoneal dialysis patients

Mao,

Huang,

Zhou

et al. 2024

Preprint

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Objectives Peritoneal dialysis (PD) patients are prone to develop vascular calcification (VC), which increases the all-cause mortality in PD patients. Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) is the inactive form of matrix Gla protein (MGP), and MGP is considered as a potent inhibitor of VC. This study is to explore the association between serum dp-ucMGP and abdominal aortic calcification (AAC) in PD patients. Methods A total 128 PD patients and 120 healthy controls were enrolled into the study. Serum dp-ucMGP was measured by enzyme-linked immunosorbent assay. Lateral plain X-ray films of abdomen were used to evaluate the abdominal aortic calcification (AAC) score (AACS). PD patients were divided into two groups according to the presence or absence of AAC. The relationships between dp-ucMGP levels and AACS were assessed by Spearman analysis and the value of dp-ucMGP in predicting AAC was evaluated by receiver operating characteristic (ROC). Results Serum dp-ucMGP in PD patients were significantly higher than controls. And PD patients with AAC had higher serum dp-ucMGP than that of PD patients without AAC. In 128 PD patients, higher dp-ucMGP was associated with greater risk of present AAC (OR = 2.554, 95%CI 1.415–4.609). The area under ROC curve of dp-ucMGP was 0.9227, the corresponding sensitivity was 0.86, and the specificity was 0.92. Conclusion Serum dp-ucMGP levels were positively associated with the AACS in PD patients. Higher serum dp-ucMGP level is independently associated with AAC in PD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Correlation between circulating dephosphorylated uncarboxylated matrix Gla protein and vascular calcification in peritoneal dialysis patients

Mao,

Huang,

Zhou

et al. 2024

Preprint

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“…A recent study on non-dialysis CKD patients suggested that a higher intake of vitamin B5 (pantothenic acid) may have a small protective effect on coronary calcification [36]. Recently, a few randomized controlled trials were designed to test the anticalcification properties of vitamin K. Trevasc-HDK failed to prove that vitamin K2 can reduce progression of coronary artery calcification in HD patients [45]. The conclusion of RenaKvit, a double-blind, randomized, placebo-controlled trial, was that vitamin K supplementation does not modify the progression of arterial calcification in dialysis [46].…”

Section: Vitamin K and Vascular Calcification In Ckdmentioning

confidence: 99%

Food to Prevent Vascular Calcification in Chronic Kidney Disease

Moldovan,

Rusu,

Potra

et al. 2024

Nutrients

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Vascular calcification (VC) is a consequence of chronic kidney disease (CKD) which is of paramount importance regarding the survival of CKD patients. VC is far from being controlled with actual medication; as a result, in recent years, diet modulation has become more compelling. The concept of medical nutritional therapy points out the idea that food may prevent or treat diseases. The aim of this review was to evaluate the influence of food habits and nutritional intervention in the occurrence and progression of VC in CKD. Evidence reports the harmfulness of ultra-processed food, food additives, and animal-based proteins due to the increased intake of high absorbable phosphorus, the scarcity of fibers, and the increased production of uremic toxins. Available data are more supportive of a plant-dominant diet, especially for the impact on gut microbiota composition, which varies significantly depending on VC presence. Magnesium has been shown to prevent VC but only in experimental and small clinical studies. Vitamin K has drawn considerable attention due to its activation of VC inhibitors. There are positive studies; unfortunately, recent trials failed to prove its efficacy in preventing VC. Future research is needed and should aim to transform food into a medical intervention to eliminate VC danger in CKD.

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“…Currently, the largest study, “Trevasc-HDK” involved 138 dialysis patients randomized to receive 360 µg of MK-7 three times weekly or placebo. At 18 months, no significant differences were documented in the primary endpoint (CAC score) or secondary endpoints (aortic valve calcification, carotid-femoral PWV, aortic augmentation index, and cardiovascular events) [ 122 ]. Again, the vitamin K2 group showed numerically better results on all VC endpoints, similar to the previous studies, while no statistical significance was reached.…”

Section: Studies Examining the Effect Of Vitamin K Supplementation In...mentioning

confidence: 99%

Vitamin K for Vascular Calcification in Kidney Patients: Still Alive and Kicking, but Still a Lot to Learn

Neofytou,

Stamou,

Demopoulos

et al. 2024

Nutrients

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Patients with chronic kidney disease (CKD) suffer disproportionately from a high burden of cardiovascular disease, which, despite recent scientific advances, remains partly understood. Vascular calcification (VC) is the result of an ongoing process of misplaced calcium in the inner and medial layers of the arteries, which has emerged as a critical contributor to cardiovascular events in CKD. Beyond its established role in blood clotting and bone health, vitamin K appears crucial in regulating VC via vitamin K-dependent proteins (VKDPs). Among these, the matrix Gla protein (MGP) serves as both a potent inhibitor of VC and a valuable biomarker (in its inactive form) for reflecting circulating vitamin K levels. CKD patients, especially in advanced stages, often present with vitamin K deficiency due to dietary restrictions, medications, and impaired intestinal absorption in the uremic environment. Epidemiological studies confirm a strong association between vitamin K levels, inactive MGP, and increased CVD risk across CKD stages. Based on the promising results of pre-clinical data, an increasing number of clinical trials have investigated the potential benefits of vitamin K supplementation to prevent, delay, or even reverse VC, but the results have remained inconsistent.

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Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK)

Cited by 5 publications

References 58 publications

Correlation between circulating dephosphorylated uncarboxylated matrix Gla protein and vascular calcification in peritoneal dialysis patients

Correlation between circulating dephosphorylated uncarboxylated matrix Gla protein and vascular calcification in peritoneal dialysis patients

Food to Prevent Vascular Calcification in Chronic Kidney Disease

Vitamin K for Vascular Calcification in Kidney Patients: Still Alive and Kicking, but Still a Lot to Learn

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