Vitamin K Supplementation for Prevention of Vascular Calcification in Chronic Kidney Disease Patients: Are We There Yet?
Roumeliotis Stefanos,Duni Anila,Vaios Vasilios,Kitsos Athanasios,Liakopoulos Vassilios,Dounousi Evangelia
Nutrients
Chronic Kidney Disease (CKD) patients are at high risk of presenting with arterial calcification or stiffness, which confers increased cardiovascular mortality and morbidity. In recent years, it has become evident that VC is an active process regulated by various molecules that may act as inhibitors of vessel mineralization. Matrix Gla Protein (MGP), one the most powerful naturally occurring inhibitors of arterial calcification, requires vitamin K as a co-factor in order to undergo post-translational γ-carboxylation and phosphrorylation and become biologically active. The inactive form of MGP (dephosphorylated, uncarboxylated dp-ucMGP) reflects vitamin K deficiency and has been repeatedly associated with surrogate markers of VC, stiffness, and cardiovascular outcomes in CKD populations. As CKD is a state of progressive vitamin K depletion and VC, research has focused on clinical trials aiming to investigate the possible beneficial effects of vitamin K in CKD and dialysis patients. In this study, we aim to review the current evidence regarding vitamin K supplementation in uremic patients.
10.3390/nu14050925
The roles of non-coding RNAs in vascular calcification and opportunities as therapeutic targets.
Ryu Juhee,Ahn Youngkeun,Kook Hyun,Kim Young-Kook
Pharmacology & therapeutics
Vascular calcification (VC) is characterized by an accumulation of calcium phosphate crystals inside the vessel wall. VC is often associated with diabetes, chronic kidney disease (CKD), atherosclerosis, and cardiovascular disease (CVD). Even though the number of patients with VC remains prevalent, there are still no approved therapies for the treatment of VC. Since the pathogenesis of VC is diverse and involves multiple factors and mechanisms, it is critical to reveal the novel mechanisms involved in VC. Although protein-coding RNAs involved in VC have been extensively studied, the roles of non-coding RNAs (ncRNAs) are not yet fully understood. The field of ncRNAs has recently received attention, and accumulating evidence from studies in VC suggests that ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play an important role in the regulation of VC. NcRNAs can modulate VC by acting as promoters or inhibitors and may be useful in the clinical diagnosis and treatment of VC. In this article, we review and discuss ncRNAs that regulate VC and present the therapeutic implications of these ncRNAs.
10.1016/j.pharmthera.2020.107675
Effect of magnesium on vascular calcification in chronic kidney disease patients: a systematic review and meta-analysis.
Renal failure
PURPOSE:To evaluate the effects of magnesium (Mg) supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD). METHODS:PubMed, Embase, Cochrane Library, Medline, Web of Science, CNKI, VIP, and WanFang databases were searched from build to July 2022. Randomized controlled trials (RCT) and non-RCT related to whether Mg supplementation inhibits VC in patients with CKD were included. The literature was screened according to inclusion and exclusion criteria, and quality evaluation and data collection were performed. Meta-analysis was performed using Review Manager 5.4 software. RESULTS:8 RCTs and 1 non-RCT studies with a total of 496 patients were eventually included. Compared to control groups, Mg supplementation increased serum Mg levels (SMD = 1.26, 95% CI: -0.70 to 1.82, < 0.001), but it was not statistically significant in alleviating the degree of VC, increasing T50, and reducing serum phosphorus (P) levels in patients with CKD (all > 0.05). Oral Mg reduced left (WMD=-0.06, 95% CI. -0.11 to -0.01, = 0.03) and right (WMD=-0.07, 95% CI: -0.13 to -0.01, = 0.02) carotid intima-media thickness (cIMT). Additionally, calcium (Ca) (SMD=-0.43, 95% CI: -0.74 to -0.11, = 0.008) and parathyroid hormone (PTH) (SMD=-0.43, 95% CI: -0.75 to -0.11, = 0.008) levels were reduced by increasing dialysate Mg concentration. CONCLUSIONS:Mg supplementation increased serum Mg levels and reduced Ca, PTH, and cIMT, but it did not reduce VC scores in patients with CKD. This still requires further studies with larger samples to evaluate the effect of Mg supplementation on VC.
10.1080/0886022X.2023.2182603
Supplementary nutrients for prevention of vascular calcification in patients with chronic kidney disease.
Lee Su Mi,An Won Suk
The Korean journal of internal medicine
Vascular calcification (VC) and malnutrition associated with cardiovascular disease are common in patients with chronic kidney disease (CKD) treated with dialysis. VC, which reflects vascular aging, and malnutrition are also encountered in the non-CKD elderly population. This similarity of clinical findings suggests that the progression of CKD is related to aging and the existence of a causal relationship between VC and malnutrition. To retard renal progression, a low- or very-low-protein diet is usually recommended for CKD patients. Dietary education may induce malnutrition and deficiency of important nutrients, such as vitamins K and D. Menaquinone-7, a type of vitamin K2, is under investigation for inhibiting VC in elderly patients without CKD, as well as for prevention of VC in patients with CKD. Nutritional vitamin D, such as cholecalciferol, may be considered to decrease the required dose of active vitamin D, which increases the risk of VC due to increased calcium and phosphate loads. Omega-3 fatty acids are important nutrients and their ability to inhibit VC needs to be evaluated in clinical trials. This review focuses on the ability of supplementary nutrients to prevent VC in patients with CKD, in whom dietary restriction is essential.
10.3904/kjim.2019.125
Pharmacological and Nutritional Modulation of Vascular Calcification.
Vossen Liv M,Kroon Abraham A,Schurgers Leon J,de Leeuw Peter W
Nutrients
Vascular calcification is an independent predictor of cardiovascular disease, and therefore, inhibition or regression of this processes is of clinical importance. The standard care regarding prevention and treatment of cardiovascular disease at this moment mainly depends on drug therapy. In animal and preclinical studies, various forms of cardiovascular drug therapy seem to have a positive effect on vascular calcification. In particular, calcium channel blockers and inhibitors of the renin-angiotensin-aldosteron system slowed down arterial calcification in experimental animals. In humans, the results of trials with these drugs are far less pronounced and often contradictory. There is limited evidence that the development of new atherosclerotic lesions may be retarded in patients with coronary artery disease, but existing lesions can hardly be influenced. Although statin therapy has a proven role in the prevention and treatment of cardiovascular morbidity and mortality, it is associated with both regression and acceleration of the vascular calcification process. Recently, nutritional supplements have been recognized as a potential tool to reduce calcification. This is particularly true for vitamin K, which acts as an inhibitor of vascular calcification. In addition to vitamin K, other dietary supplements may also modulate vascular function. In this narrative review, we discuss the current state of knowledge regarding the pharmacological and nutritional possibilities to prevent the development and progression of vascular calcification.
10.3390/nu12010100
Biomimetic Grapefruit-Derived Extracellular Vesicles for Safe and Targeted Delivery of Sodium Thiosulfate against Vascular Calcification.
ACS nano
As the prevalence of vascular calcification (VC), a strong contributor to cardiovascular morbidity and mortality, continues to increase, the need for pharmacologic therapies becomes urgent. Sodium thiosulfate (STS) is a clinically approved drug for therapy against VC; however, its efficacy is hampered by poor bioavailability and severe adverse effects. Plant-derived extracellular vesicles have provided options for VC treatment since they can be used as biomimetic drug carriers with higher biosafety and targeting abilities than artificial carriers. Inspired by natural grapefruit-derived extracellular vesicles (EVs), we fabricated a biomimetic nanocarrier comprising EVs loaded with STS and further modified with hydroxyapatite crystal binding peptide (ESTP) for VC-targeted delivery of STS. , the ESTP nanodrug exhibited excellent cellular uptake capacity by calcified vascular smooth muscle cells (VSMCs) and subsequently inhibited VSMCs calcification. In the VC mice model, the ESTP nanodrug showed preferentially the highest accumulation in the calcified arteries compared to other treatment groups. Mechanistically, the ESTP nanodrug significantly prevented VC via driving M2 macrophage polarization, reducing inflammation, and suppressing bone-vascular axis as demonstrated by inhibiting osteogenic phenotype trans-differentiation of VSMCs while enhancing bone quality. In addition, the ESTP nanodrug did not induce hemolysis or cause any damage to other organs. These results suggest that the ESTP nanodrug can prove to be a promising agent against VC without the concern of systemic toxicity.
10.1021/acsnano.3c05261