Vitamin K deficiency in CKD patients: a modifiable risk factor for vascular calcification?

Abstract Background and Aims Two Vitamin K-dependent proteins (VDKPs) link bone and vasculature in CKD-MBD: Bone Gla Protein (BGP) and Matrix Gla Protein (MGP). In ESKD, Vitamin K deficiency is highly prevalent and leads to increased levels of inactive VKDPs (undercaboxylated (ucBGP and dephosphorylated (dp)-uMGP), which are linked to greater risk of fractures and severity of vascular calcification. We hypothesized that kidney transplantation (KT) would improve Vitamin K status and lower levels of inactive VKDPs. Method Between 2014-2017, we conducted a study in 34 patients to assess changes in VKDPs during the 1st year of KT. In a specialized lab we determined VKDPs pre- and 1-year post-KT: total BGP, uc BGP, total MGP, and dp-uc MGP. We determined the prevalence of Vitamin K deficiency based on levels of uc BGP and dp-uc MGP. Results Our cohort had a mean +/- SD age of 48+/-14 years, 32% were female and 97% were Caucasian. 1 year post-KT, there was a decrease in the levels of all VKDPs and the prevalence of Vitamin K deficiency (Table 1 and Figure 1). Patients with greatest severity of Vitamin K deficiency pre-KT had the largest decreases of inactive VDKPs post-KT. Conclusion KT was associated with improvement in Vitamin K status as manifested by decreased levels of inactive VKDPs. These are the first prospective data on VKDPs in CKD patients pre- and post-KT. Studies are needed to assess the impact of improvement in VKDP status after KT on CKD-MBD outcomes.

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Vitamin K deficiency: an emerging player in the pathogenesis of vascular calcification and an iatrogenic consequence of therapies in advanced renal disease

AJP Renal Physiology ◽

10.1152/ajprenal.00278.2020 ◽

2020 ◽

Vol 319 (4) ◽

pp. F618-F623

Author(s):

David S. Levy ◽

Rickinder Grewal ◽

Thu H. Le

Keyword(s):

Bone Metabolism ◽

Vascular Calcification ◽

Vitamin K ◽

Hospital Admissions ◽

Fibroblast Growth Factor 23 ◽

Vitamin K Deficiency ◽

Increased Risk ◽

K Deficiency ◽

Human Aortic Valve

Vascular calcification is a known complication of chronic kidney disease (CKD). The prevalence of vascular calcification in patients with non-dialysis-dependent CKD stages 3–5 has been shown to be as high as 79% ( 20 ). Vascular calcification has been associated with increased risk for mortality, hospital admissions, and cardiovascular disease ( 6 , 20 , 50 , 55 ). Alterations in mineral and bone metabolism play a pivotal role in the pathogenesis of vascular calcification in CKD. As CKD progresses, levels of fibroblast growth factor-23, parathyroid hormone, and serum phosphorus increase and levels of 1,25-(OH)2 vitamin D decrease. These imbalances have been linked to the development of vascular calcification. More recently, additional factors have been found to play a role in vascular calcification. Matrix G1a protein (MGP) in its carboxylated form (cMGP) is a potent inhibitor of vascular calcification. Importantly, carboxylation of MGP is dependent on the cofactor vitamin K. In patients with CKD, vitamin K deficiency is prevalent and is exacerbated by warfarin, which is frequently used for anticoagulation. Insufficient bioavailability of vitamin K reduces the amount of cMGP available, and, therefore, it may lead to increased risk of vascular calcification. In vitro studies have shown that in the setting of a high-phosphate environment and vitamin K antagonism, human aortic valve interstitial cells become calcified. In this article, we discuss the pathophysiological consequence of vitamin K deficiency in the setting of altered mineral and bone metabolism, its prevalence, and clinical implications in patients with CKD.

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Is vitamin K deficiency a risk factor for osteoporosis in Crohn's disease?

The Lancet ◽

10.1016/s0140-6736(00)05135-7 ◽

2001 ◽

Vol 357 (9273) ◽

pp. 1995-1996 ◽

Cited By ~ 21

Author(s):

Pawel Szulc ◽

Pierre Jean Meunier

Keyword(s):

Risk Factor ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Vitamin K ◽

Vitamin K Deficiency ◽

K Deficiency

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Functional vitamin K insufficiency, vascular calcification and mortality in advanced chronic kidney disease: A cohort study

PLoS ONE ◽

10.1371/journal.pone.0247623 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0247623

Author(s):

Lu Dai ◽

Longkai Li ◽

Helen Erlandsson ◽

Armand M. G. Jaminon ◽

Abdul Rashid Qureshi ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Vascular Calcification ◽

Vitamin K ◽

Matrix Gla Protein ◽

Vitamin K Deficiency ◽

Increased Risk ◽

Ckd Stage ◽

All Cause Mortality ◽

K Deficiency

Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01–1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01–1.48 and 1.27, 1.01–1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.

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Current Therapy in CKD Patients Can Affect Vitamin K Status

Nutrients ◽

10.3390/nu12061609 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1609 ◽

Cited By ~ 2

Author(s):

Mario Cozzolino ◽

Giuseppe Cianciolo ◽

Manuel Alfredo Podestà ◽

Paola Ciceri ◽

Andrea Galassi ◽

...

Keyword(s):

Vascular Calcification ◽

Vitamin K ◽

Bone Mineralization ◽

Current Therapy ◽

Phosphate Binders ◽

Mineral Density ◽

Vitamin K Deficiency ◽

Mineral And Bone Disorder ◽

Related Risk ◽

K Deficiency

Chronic kidney disease (CKD) patients have a higher risk of cardiovascular (CVD) morbidity and mortality compared to the general population. The links between CKD and CVD are not fully elucidated but encompass both traditional and uremic-related risk factors. The term CKD-mineral and bone disorder (CKD-MBD) indicates a systemic disorder characterized by abnormal levels of calcium, phosphate, PTH and FGF-23, along with vitamin D deficiency, decreased bone mineral density or altered bone turnover and vascular calcification. A growing body of evidence shows that CKD patients can be affected by subclinical vitamin K deficiency; this has led to identifying such a condition as a potential therapeutic target given the specific role of Vitamin K in metabolism of several proteins involved in bone and vascular health. In other words, we can hypothesize that vitamin K deficiency is the common pathogenetic link between impaired bone mineralization and vascular calcification. However, some of the most common approaches to CKD, such as (1) low vitamin K intake due to nutritional restrictions, (2) warfarin treatment, (3) VDRA and calcimimetics, and (4) phosphate binders, may instead have the opposite effects on vitamin K metabolism and storage in CKD patients.

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Vitamin K Deficiency and Vascular Calcification. Is There Any Evidence about Its Impact on Coronary Artery Disease?

10.5772/intechopen.99335 ◽

2021 ◽

Author(s):

Theodoros Michailidis ◽

Asterios Karakanas ◽

Nikolaos Schizas ◽

Petros Keryttopoulos

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Vascular Calcification ◽

Vitamin K ◽

Cardiovascular Events ◽

Rapid Progression ◽

Vitamin K Deficiency ◽

K Deficiency ◽

Artery Disease ◽

K Depletion

Nowadays cardiovascular disease remain globally the leading cause of mortality. Coronary artery disease is the predominant clinical entity related to fatal cardiovascular events, while its development is mostly associated with progressive atherosclerosis of the vessels combined with gradual vascular calcification. It is well described and understood that vascular calcification is strongly associated with the occurrence of CVD and increased mortality rates. Therefore, it is essential to understand the metabolic pathways leading to its formation in order to develop effective therapies. A group of vitamin-k dependent proteins seems to play a significant role on the prevention of the arterial wall. Several past studies have shown that in cases of vitamin-k deficiency the process of vessel calcification is accelerated. Vitamin-k depletion and high levels of uncarboxylated and dephosphorylated forms of the aforementioned proteins are considered as important factors that contribute significantly to this rapid progression. Promising studies are giving the stimulus for further research in the field of vitamin-k supplementation and the suspension of vascular calcification.

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Hydrolysed Formula Is a Risk Factor for Vitamin K Deficiency in Infants With Unrecognised Cholestasis

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/mpg.0b013e3181efb0b3 ◽

2010 ◽

Vol 51 (6) ◽

pp. 773-776 ◽

Cited By ~ 5

Author(s):

PM van Hasselt ◽

W de Vries ◽

E de Vries ◽

K Kok ◽

ECM Cranenburg ◽

...

Keyword(s):

Risk Factor ◽

Vitamin K ◽

Vitamin K Deficiency ◽

K Deficiency ◽

Hydrolysed Formula

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Review article - Impact of Vitamin K on Human Health

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol30iss1pp1-13 ◽

2021 ◽

Vol 30 (1) ◽

pp. 1-13

Author(s):

Najwan K. Fakhree ◽

Sarah H. Mhaibes ◽

Heba H. Khalil

Keyword(s):

Insulin Resistance ◽

Risk Factor ◽

Vitamin K ◽

Blood Clotting ◽

Review Article ◽

Hepatic Tissue ◽

Vitamin K Deficiency ◽

Daily Dose ◽

K Deficiency ◽

Article Impact

Vitamins k is an important fat-soluble vitamin that can be obtained from plants, bacteria and animals and is necessary for the blood clotting. It plays a key function as a cofactor in the synthesizing of blood clotting proteins in the liver; recently, the interest for its functions in extra-hepatic tissue has increased. Vitamin k deficiency is usually caused by abnormal absorption rather than in the lack of vitamin in food. Apart from its impact on clotting, chronic subclinical deficiency of vitamin K maybe a risk factor for many diseases such as osteoporosis, atherosclerosis, cancer, insulin resistance, neurodegenerative diseases and others, while current food intake guidelines be focused on the daily dose necessary to avoid blood loss. Several researchers found out that vitamin K needs may be substantially higher for certain health functions.

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MO903THE ASSOCIATION BETWEEN VITAMIN K, CALCIUM, PHOSPHORUS LEVELS AND NUTRITIONAL STATUS IN HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab102.004 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Sylwia Małgorzewicz ◽

Ewelina Puchalska-Reglińska ◽

Lucyna Konieczna ◽

Katarzyna Krzanowska ◽

Alicja Debska-Slizien

Keyword(s):

Nutritional Status ◽

Vascular Calcification ◽

Vitamin K ◽

Matrix Protein ◽

Dietary Assessment ◽

Hemodialysis Patients ◽

Vitamin K Deficiency ◽

Calcium Phosphorus ◽

K Deficiency ◽

Phosphorus Levels

Abstract Background and Aims Vascular calcification is highly prevalent in dialysis patients. The most common postulated cause, apart from calcium and phosphorus disorders, is sub-clinical vitamin K deficiency. It results in the failure of the GLA-matrix protein (MGP) to undergo carboxylation. The lack of functional carboxylated MGP may contribute to increased vascular calcification. Aim: We assessed the relationships between vitamin K, MGP, calcium, phosphorus levels and nutritional status in hemodialysis patients. Method The study included 58 hemodialysis patients in stable clinical condition (mean age 64.1 ± 15.6 yr) . We determined plasma levels of: vitamin K1 and K2 (LC-MS method), GLA -matrix protein (ucMGP and cMGP), osteocalcin (ELISA methods), parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), CRP and routine biochemistry. Echocardiography was performed and BMI was calculated. Nutritional status was assessed by SGA and s-albumin – malnutrition was diagnosed based SGA ≤5 and s-albumin ≤ 38g/l. FFQ-6 was used to dietary assessment. Patients with HPT (n=17; 32%) were treated by active vitamin D/paricalcitrol and calcium carbconicum. Results Malnourished patients (n=11; 20%) presented statistically significantly higher CRP, age and lower phosphorus, iPTH, BUN, creatinine, cholesterol and potassium. Also, malnourished patients presented significantly higher ucMGP and lower cMGP and lower both vitamin K forms in comparison to well-nourished (ucMGP 18.9 vs 13.2 ng/dl; p=0.0005; cMGP 150.1 vs 332.4 ng/dl; p=0.0002). Diet in both groups malnourished and well-nourished not differ significantly, though malnourished patients ate less amount of nutrients. Additionally, phosphorus level positively correlated with Kt/V, SGA and vitamin K2 (R Spearman =- 0.3;p=0.01,R Spearman = 0.4;p=0.05;R Spearman = 0.3; p=0.001, respectively). Conclusion Vitamin K deficiency, as expressed by high ucMGP levels is associated with nutritional status. Low albumin and chronic inflammation might increase risk of calcification in spite relatively low iPTH and phosphorus levels.

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