Vitamin Ok in Power Kidney Illness

Results from the Dialysis Outcomes and Practice Patterns Study
March 16, 2021 0 Comments

Vitamins. 2019 Jan; 11(1): 168.

Summary

Vitamin Ok is a composite time period referring to a gaggle of fat-soluble nutritional vitamins that operate as a cofactor for the enzyme γ-glutamyl carboxylase (GGCX), which prompts various vitamin Ok-dependent proteins (VKDPs) concerned in haemostasis and vascular and bone well being. Accumulating proof demonstrates that persistent kidney illness (CKD) sufferers endure from subclinical vitamin Ok deficiency, suggesting that this represents a inhabitants in danger for the organic penalties of poor vitamin Ok standing. This deficiency is likely to be brought on by exhaustion of vitamin Ok on account of its excessive necessities by vitamin Ok-dependent proteins to inhibit calcification.

Key phrases: vitamin Ok, CKD, vascular calcification

1. Introduction

There are two types of vitamin Ok: K1 (phylloquinone, PK) primarily present in inexperienced greens, and K2 (together with completely different menaquinones, MKs) derived from intestinal micro organism and fermented meals (cheeses and “natty”, a Japanese soybean product) [1,2]. Liver can also be a wealthy supply of menaquinones [3]. We find out about greater than 12 several types of MKs, from MK-4 to MK-15, however the most typical MKs in people are the short-chain MK-4; it’s the solely MK produced by systemic conversion of phylloquinone to menaquinones [4].

Vitamin Ok is a non-polar molecule; after its intestinal absorption, vitamin okay is solubilised by bile salt and pancreatic juice; vitamin Ok is then packaged into chylomicrons that are secreted into the lymphatic system [5]. For that reason lipids, specifically triglycerides, intrude with vitamin Ok measurement.

Vitamin Ok is as a substrate for an enzyme, the vitamin Ok-dependent carboxylase, that converts particular glutamic acid residues of a small variety of proteins to glutamic carboxyl (Gla) residues by the addition of a CO2. Vitamin Ok is important to introduce carboxyl teams into glutamic acid residues in blood coagulation elements (II, VII, IX, X) to yield Gla residues [6]; Gla-containing proteins embrace osteocalcin (OC), synthesized by the osteoblasts in bone, and matrix Gla protein (MGP), synthesized by chondrocytes and vascular easy muscle cells (VSMCs), concerned in bone mineralization and inhibition of vascular calcifications, respectively.

2. Vitamin Ok Deficiency

Oblique purposeful assessments may be assessed to detect vitamin okay ranges, such because the prothrombin time or measurement of undercarboxylated proteins OC and MGP, that are extra delicate in detecting subclinical vitamin Ok deficiency than prothrombin time [6]. This measurement is feasible as a result of vitamin Ok-dependent proteins (VKDP) can’t attain their carboxylation standing (they usually stay undercarboxylated) within the presence of vitamin Ok deficiency; this situation causes the lack of their capability to bind calcium, in order that bone metabolism could also be impaired and the method of vascular calcification enhanced [7]. A excessive share of undercarboxylated OC (uOC) displays vitamin Ok consumption and the long-term vitamin Ok standing. Osteocalcin ranges are additionally influenced by vitamin D, which is required for the manufacturing of uOC, and by parathyroid hormone (PTH), which is continuously elevated in CKD sufferers [6,8,9]. Subsequently, persistent kidney illness (CKD) sufferers with hyperparathyroidism will current excessive serum uOC, however this doesn’t essentially imply that they’re vitamin Ok poor.

A very good various to judge vitamin Ok standing is thru the inactive type of MGP, even when inactive MGP might solely replicate the vitamin Ok standing on the vascular degree and never at bone or liver. Certainly, randomized managed research have proven that vitamin Ok remedy decreases undercarboxylated unphosphorylated MGP (uc-dp-MGP) ranges [9,10,11]; in distinction, anti-vitamin Ok (AVK) therapy elevated the quantity of inactive uc-dp-MGP [12] and stopping that therapy decreased uc-dp-MGP [13]. All these knowledge recommend that uc-dp-MGP could possibly be a very good marker of vitamin Ok standing [6].

3. Vitamin Ok Standing in CKD Sufferers

Proof demonstrates that CKD sufferers endure from subclinical vitamin Ok deficiency [14], suggesting that this inhabitants is in danger for any penalties of poor vitamin Ok standing. This deficiency is likely to be brought on by exhaustion of vitamin Ok on account of its excessive requirement by vitamin Ok-dependent proteins to inhibit calcification. Nevertheless, dietary suggestions for CKD sufferers, reminiscent of diets low in potassium (fewer leafy inexperienced greens wealthy in K1) and low in phosphate (fewer dairy merchandise wealthy in K2) might promote this deficiency.

Contemplating that vitamin Ok is important for the activation of matrix Gla protein (MGP), a strong inhibitor of tissue calcification, purposeful vitamin Ok deficiency might contribute to excessive vascular calcification (VC) burden in haemodialysis sufferers; that is course of during which mineral is pathologically deposited in blood vessels, primarily in massive elastic and muscular arteries such because the aorta and the coronary, carotid, and peripheral arteries. The presence of VC is immediately associated to elevated cardiovascular morbidity and mortality in dialysis sufferers [15].

Circulating non-phosphorylated non-carboxylated MGP, which is shaped because of vitamin Ok deficiency in CKD, is related to heart problems and with general survival [16]; in distinction, in older people with out CKD, non-carboxylated MGP was linked to irregular vitamin Ok standing, however to not coronary artery calcium content material [17]. Shea et al. [17] reported the latter situation, and these findings are in distinction with outcomes of case–management research reporting increased plasma ucMGP amongst sufferers with illnesses characterised by vascular calcification and kidney illness; nevertheless, the prior research didn’t measure CAC immediately as they’ve. Moreover, the ucMGP could also be a marker for different threat elements, reminiscent of hyperlipidaemia and hypertension [17].

Schurgers et al. measured dpucMGP in a cohort of 107 sufferers starting from CKD levels 2–5D, and reported that ranges of plasma dp-ucMGP elevated progressively with CKD stage. They confirmed, subsequently, a decline on this biomarker with discount in GFR [18]; the danger of vascular calcification is presumed increased if the calcification-inhibitory impact of MGP is impaired. Pre-clinical research affirm that diminished vitamin Ok standing influences the severity of arterial calcification in rats with CKD that may be prevented by a weight loss plan wealthy in vitamin K1 [19].

Holden et al., in a examine of 172 stage 3–5 CKD sufferers, demonstrated that over 50% consumed lower than the beneficial enough consumption for vitamin Ok; furthermore, 6% have been vitamin Ok-insufficient in accordance with low ranges of serum phylloquinone (<0.4 ng/mL), 60% were insufficient according to high levels of ucOC (>20% ucOC), and 97% have been inadequate in accordance with excessive ranges of protein-induced vitamin Ok absence or antagonist II (PIVKA-II) (>2 nmol/L) [20].

A number of research targeted on the vitamin Ok standing in haemodialysis (HD) sufferers [21]. On account of its lipophilic traits, vitamin Ok wouldn’t be anticipated to be eliminated by way of the dialysis process however there’s a rising and constant physique of proof supporting the notion that upkeep HD sufferers have a worldwide poor vitamin Ok standing; whereas the precise motive for the low consumption is unknown, it’s possible associated to the dietary routine prescribed for HD sufferers and general poor nutrient consumption.

As reported by Westenfeld et al., at baseline, haemodialysis sufferers had 4.5-fold increased dephosphorylated, uncarboxylated MGP and eight.4-fold increased uncarboxylated osteocalcin ranges in contrast with controls [11]. Cranenburg et al. measured and assessed vitamin K1 and K2 consumption and the vitamin Ok standing in 40 haemodialysis sufferers: the consumption was low in these sufferers (median 140 µg/day), particularly on days of dialysis and the weekend as in comparison with intakes reported in a reference inhabitants of wholesome adults (imply K1 and K2 consumption 200 and 31 µg/day, respectively) [14]. In response to poor dietary consumption, physique shops of vitamin Ok are quickly depleted. Undercarboxylated vitamin Ok-dependent bone and coagulation proteins have been discovered to be elevated in 33 haemodialysis sufferers, indicating subclinical hepatic vitamin Ok deficiency. Very excessive non-carboxylated MGP ranges, endemic to all sufferers, additionally strongly advised vascular vitamin Ok deficiency.

Voong et al. reported that 29% and 93% of upkeep HD sufferers met standards for sub-clinical vitamin Ok deficiency based mostly on low ranges of phylloquinone and excessive ranges of ucOC, suggesting there’s additionally vitamin Ok deficiency on the degree of bone [22].

Some research demonstrated that peritoneal dialysis (PD) sufferers have an analogous diploma of vitamin Ok insufficiency as upkeep HD sufferers: in a examine of 28 PD sufferers, 46% had vitamin Ok deficiency as measured by elevated PIVKA II ranges (>2 nM/L) [23]. In a cross-sectional examine of 21 PD sufferers, it was demonstrated that 24% of them had vitamin Ok deficiency as assessed by serum K1 (<0.4 nM/L) and all patients had vitamin K deficiency as assessed by increased percentage of ucOC (>20% was the minimize off for vitamin Ok deficiency, imply was 60%) [24].

Jansz et al. studied the affect of kidney transplantation and phosphate binder use on vitamin Ok standing and located that kidney transplant recipients have considerably decrease dp-ucMGP ranges in comparison with sufferers on haemo- or peritoneal dialysis, indicating higher vitamin Ok standing after restoration of kidney operate. Normally, as a substitute, phosphate binder use will not be related to dp-ucMGP ranges aside from sevelamer monotherapy. which is related to considerably increased dp-ucMGP ranges, suggesting a detrimental impact of sevelamer on vitamin Ok standing [25].

4. Anti-Vitamin Ok Therapy and Results—Warfarin

Warfarin is a vitamin Ok antagonist; its use represents a mannequin of vitamin Ok insufficiency. It induces arterial calcification in experimental fashions, however whether or not this happens in people is unclear.

Tantisattamo et al. [26] examined breast arterial calcification recognized on mammograms. Screening mammograms from girls with present, previous, or future warfarin use have been examined for the presence of arterial calcification and in contrast with mammograms obtained in untreated girls matched for age and diabetes mellitus. In 451 girls with mammograms carried out after ≥1 month of warfarin remedy, the prevalence of arterial calcification was 50% higher than in 451 untreated girls (39.0% versus 25.9%; p < 0.0001). This examine confirmed that the prevalence of breast arterial calcification is elevated in girls with present or previous warfarin use unbiased of different threat elements and situations predating warfarin use; this impact could also be irreversible and seems to be cumulative.

McCabe at al. [19] needed to find out whether or not modifying vitamin Ok standing, both by growing dietary vitamin Ok consumption or by antagonism with therapeutic doses of warfarin, might alter the event of vascular calcification in male Sprague–Dawley rats with adenine-induced CKD. Pulse strain and pulse wave velocity have been elevated after therapy with warfarin in CKD rats, in addition to calcium concentrations within the thoracic aorta (3-fold), stomach aorta (8-fold), renal artery (4-fold), and carotid artery (20-fold) have been considerably elevated. It’s fascinating to note that therapeutic warfarin didn’t induce calcification within the blood vessels of wholesome rats regardless of depletion of tissue vitamin Ok; in distinction, in contrast with CKD alone, warfarin markedly elevated the degrees of vascular calcification in all vessels studied within the presence of CKD.

Thus, vitamin Ok has an vital position in modifying mechanisms linked to the susceptibility of arteries to calcify in an experimental mannequin of CKD.

In addition to presenting a higher threat of improvement of vascular calcifications on account of secondary hyperparathyroidism, haemodialysis sufferers are continuously handled with vitamin Ok antagonists, primarily to stop stroke in atrial fibrillation, probably compounding the cardiovascular threat in these already weak sufferers. Warfarin might predispose to completely different facet impact, reminiscent of bone fractures and vascular calcification, by completely different mechanisms: immediately, by inhibition of carboxylation of OC and different bone matrix proteins; not directly, as a result of sufferers handled with warfarin might restrict their dietary consumption of meals wealthy in vitamin Ok [18,19].

4.1. Bone Fracture

Research on bone fractures in CKD sufferers are restricted. In accordance with the out there literature, the prevalence of vertebral fractures in dialysis sufferers seems to be just like the overall inhabitants, between 20.9% and 26.5% [27,28]; nevertheless Rodriguez-Garcia et al. [29] demonstrated a constructive, important correlation between vertebral fractures and vascular calcification within the dialysis inhabitants. That is in all probability on account of underdiagnosis of vertebral fractures each within the normal and within the dialysis inhabitants; this speculation was confirmed by the unpublished knowledge of Fusaro et al., during which a vertebral fracture prevalence of 57% was present in a inhabitants of 68 haemodialysis sufferers [7]. Alem et al. studied the incidence of hip fractures they usually discovered a significantly increased threat of hip fracture amongst dialysis sufferers than typically inhabitants [30].

Kohlmeier et al. have been the primary to exhibit an unbiased affiliation between poor vitamin Ok standing and threat of bone fracture in sufferers in haemodialysis [31], whereas Fusaro et al. carried out an observational examine of 387 prevalent HD, figuring out that over 50% of prevalent haemodialysis sufferers have vertebral fractures [32]. On this examine, vitamin K1 deficiency (outlined as a phylloquinone degree adjusted for serum triglycerides <0.21 ng/mL), was the strongest predictor for the presence of a vertebral fracture (an adjusted odds ratio approaching 3).

In one other examine, Fusaro et al. discovered that haemodialysis sufferers handled with warfarin for higher than 1 yr had an elevated threat of vertebral fractures in comparison with these not on warfarin therapy [33]. With regard to vitamin Ok administration for the prevention of fractures, 13 randomized managed research with vitamin K1 and K2 therapy lasting for no less than 6 months have been the topic of a meta-analysis [34]: 11 of those research have been from Japan, and 7 reported fracture knowledge. The themes recruited within the research have been primarily menopausal girls. All however one research confirmed a bonus of vitamin Ok in lowering bone loss. All seven trials that reported fracture results have been from Japan and used vitamin K2 (menaquinone). Pooling the seven trials with fracture knowledge in a meta-analysis, an odds ratio favouring menaquinone of 0.40 (95% confidence interval (CI), 0.25–0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12–0.47) for hip fractures, and an OR of 0.19 (95% CI, 0.11–0.35) for all nonvertebral fractures have been reported.

4.2. Cardiovascular Calcification

The primary examine [35] demonstrating strongly elevated calcification of the aortic valves in sufferers taking oral anticoagulants—together with warfarin and acenocoumarol—has been confirmed by many different researchers: Koos et al. demonstrated that topics taking vitamin Ok antagonist anticoagulants had a considerably increased diploma of arterial and aortic valve calcification than management topics [36]. In a case report, Hristova et al. described a kidney transplant recipient exhibiting huge arterial calcification after the initiation of warfarin remedy [37]. Distal subcutaneous necrosis in the end led to the affected person’s dying. Rennenberg et al. confirmed speedy calcification of the femoral artery when sufferers are handled with oral anticoagulants, (OR 8.5; 95% confidence interval (CI) 2.01–35.95, for calcification in sufferers in contrast with controls) [38]. Equally, sufferers taking oral anticoagulants confirmed considerably elevated ranges of coronary calcification [39].

4.3. Calciphylaxis

Roughly 1% of CKD sufferers develop calciphylaxis, a continuously deadly complication of end-stage renal illness. Notably, about 50% of sufferers with CKD stage 5D (CKD5D) who develop calciphylaxis are on vitamin Ok antagonists (VKAs) [40]. In comparison with the dialysis sufferers worldwide, the general variety of calciphylaxis instances is minimal. Nevertheless, of their case–management evaluation, Hayashi et al. [41], calculated an 11.4-fold elevated threat of growing calciphylaxis in Japanese dialysis sufferers on warfarin.

Within the pilot case–management examine by Nigwekar et al. the authors demonstrated that sufferers with calciphylaxis in finish stage renal illness (ESRD) had proportionally increased plasma ranges of the inactive ucMGP than dialysis controls. They investigated how MGP carboxylation influenced the danger of calciphylaxis in 20 sufferers receiving haemodialysis with calciphylaxis (instances) and 20 sufferers receiving haemodialysis with out calciphylaxis (controls); case sufferers had increased plasma ranges of ucMGP and carboxylated MGP (cMGP) than controls. Nevertheless, the fraction of complete MGP that was carboxylated (relative cMGP focus = cMGP/(cMGP + uncarboxylated MGP)) was decrease in instances than in controls (0.58 ± 0.02 versus 0.69 ± 0.03, respectively; p = 0.003). The authors concluded {that a} vitamin Ok deficiency-mediated discount in relative cMGP focus might have a job within the pathogenesis of calciphylaxis [42].

Krueger et al. imagine that vitamin Ok, and particularly vitamin K2, supplementation might turn out to be an vital possibility in the usual therapy for calcification-prone CKD sufferers [43].

4.4. Arteriovenous Fistula Failure

Arteriovenous fistula (AVFs) is a continuously used vascular entry sort for CKD sufferers requiring haemodialysis (HD) [44]. AVF failure is a complication resulting in excessive hospitalization charges and morbidity [45]. Whereas early AVF failure is brought on by thrombosis or by incapacity of the vein to dilate, later course AVF failure is induced by stenosis and thrombosis ensuing from neointimal hyperplasia (NIH) and calcification [46,47]. Latest work signifies that AVF calcification contributes to AVF failure [48]; in arterialized veins, calcification happens in tunica media and intima. HD sufferers have a poor general vitamin Ok standing, and a excessive variety of CKD sufferers susceptible to arterial and venous thrombosis obtain oral anticoagulants (vitamin Ok antagonists; VKAs) [49]. It has been proven that VSMCs from varicose veins elevated calcification when handled with warfarin, indicating comparable processes in venous and arterial VSMCs [50]. Vascular entry calcification is an unbiased predictor of mortality, whereas nothing is thought about results of VKA on AVF, NIH, and calcification.

The target of the examine of Zaragatski et al. was to research the consequences of vitamin Ok antagonists and vitamin K2 therapy on neointimal hyperplasia improvement and calcification in rats and in arterialized human veins [51]. AVF was generated in feminine rats whereas persistent kidney illness was induced utilizing an adenine-enriched weight loss plan. Arterialization, CKD, and vitamin Ok antagonists all considerably enhanced venous neointimal hyperplasia. K2 therapy and vitamin Ok antagonists considerably lowered neointimal hyperplasia in arterialized veins in wholesome rats however not in rats with CKD. Arterialization, CKD, and vitamin Ok antagonism all considerably elevated, whereas K2 supplementation attenuated calcification in wholesome rats and rats with CKD.

K2 considerably enhanced matrix Gla protein carboxylation in management rats and rats with CKD. Arterialized human vein samples contained inactive matrix Gla protein at calcification and neointimal hyperplasia websites, indicating native vitamin Ok deficiency. Thus, vitamin Ok antagonists have detrimental results on AVF transforming, whereas K2 lowered neointimal hyperplasia and calcification indicating vasoprotective results. Therefore, K2 administration could also be helpful to stop neointimal hyperplasia and calcification in arterialized veins.

5. New Oral Anticoagulant vs. Warfarin

New oral anticoagulants (NOACs) are legitimate options to vitamin Ok antagonists within the normal inhabitants, however their use in dialysis has been restricted by substantial renal clearance.

Dabigatran and rivaroxaban haven’t been studied in end-stage renal illness sufferers who have been particularly excluded from two massive randomized trials that have been carried out in sufferers with out renal failure [52,53]. In dialysis sufferers, prescription of those novel oral anticoagulant medicine (NOACs) is at the moment contraindicated as a result of the medicine are cleared by kidneys and drug ranges can bio-accumulate to precipitate bleeding; as demonstrated by Chan et al., the unadjusted occasion charge of main bleeding elevated with drug dosage [54]. The examine of Chan et al. is the primary to judge these medicine within the dialysis inhabitants, and suggests concern given the growing use of dabigatran and rivaroxaban within the ESRD inhabitants regardless of formal FDA warnings of warning in renal failure. Actually, their secondary analyses recommend extra morbidity and mortality from bleeding associatively increased with dabigatran and rivaroxaban when in comparison with warfarin [54].

Among the many out there NOACs, apixaban has the bottom renal elimination. Each dabigatran and rivaroxaban have been related to elevated bleeding in dialysis sufferers however not too long ago apixaban was non-inferior to warfarin in a big database examine.

Siontis et al. [55] carried out a retrospective cohort examine in sufferers with ESRD and atrial fibrillation (AF) in dialysis who initiated therapy with apixaban or warfarin. Commonplace dose of apixaban (5 mg twice a day) was related to considerably decrease dangers of stroke/systemic embolism and dying as in contrast with both lowered dose of apixaban (2.5 mg twice a day; n = 1317; HR 0.61, 95% CI 0.37–0.98, p = 0.04 for stroke/systemic embolism; and HR 0.64, 95% CI 0.45–0.92, p = 0.01 for dying) or warfarin (HR 0.64, 95% CI 0.42–0.97, p = 0.04 for stroke/systemic embolism; and HR 0.63, 95% CI 0.46–0.85, p = 0.003 for dying). The authors concluded that, amongst ESRD sufferers with AF on dialysis, apixaban use could also be related to decrease threat of main bleeding in contrast with warfarin, with a normal 5 mg twice a day dose additionally related to reductions in thromboembolic and mortality threat.

6. Phosphate Binders

Power kidney illness mineral bone problems (CKD-MBD) is a fancy syndrome in dialysis sufferers, which incorporates alterations of biochemical parameters of the mineral and bone metabolism, a clinically and histologically manifested bone illness and vascular calcifications related to an elevated threat of cardiovascular morbidity and mortality. One in every of its most frequent elements is hyperphosphatemia, which has historically been handled with dietary restrictions and intestinal phosphorus binders [56].

It’s unknown if using phosphate binders, particularly calcium based mostly binders, may very well be dangerous [57]. There may be some attenuation or delay of development of VC by the noncalcium-based phosphate binders as in comparison with the calcium containing binders [58,59,60]. Nevertheless VC continuously progresses regardless of enough phosphate concentrations; in all probability on account of persistent irritation, growing calcium load from calcium based mostly binders and different elements reminiscent of vitamin Ok deficiency.

Of their examine, Neradova et al. arrange a examine during which vitamin K2 (menaquinone-7; MK-7) was blended with 5 completely different phosphate binders, in presence or absence of phosphate, incubated at pH 6 and glued temperature of 37 levels Celsius. Specifically, 1 mg of vitamin K2 was added to a medium with pH 6 containing 67 mg phosphate binder with both 7 mg of phosphate or no phosphate [61].

This experiment confirmed that sucroferric-oxyhydroxide and sevelamer carbonate have been the one binders that didn’t bind vitamin K2 in vitro. This in vitro examine demonstrated that calcium acetate/magnesium carbonate binds vitamin K2 strongly each in absence (p = 0.001) and presence of phosphate (p = 0.003). For Lanthanum carbonate this binding is determined by the absence of phosphate, pointing to aggressive binding between phosphate and vitamin K2 for this compound (p = 0.005) whereas no important binding of vitamin K2 was noticed within the answer containing vitamin K2 and phosphate (p = 0.462). Calcium carbonate binds vitamin K2 statistically and considerably in an answer with vitamin K2 and phosphate (p = 0.009), whereas with out phosphate no important binding of vitamin K2 was noticed (p = 0.123). Within the combination with sevelamer carbonate a nominally decrease focus of K2 was proven as effectively, however this decline was not statistically important. Addition of sucroferric-oxyhydroxide didn’t result in any decline of vitamin K2 in any respect, regardless of presence or absence of phosphate.

The authors didn’t examine the chemical rationalization for this function, however probably the shaped calcium-phosphate salt itself binds K2 as effectively. In conclusion, the presence or absence of phosphate considerably interferes with vitamin K2 binding, so phosphate binders might probably restrict the bioavailability of vitamin K2.

In accordance with these outcomes, in HD sufferers, during which phosphorus ranges are normally elevated, phosphate binders that don’t bind vitamin Ok within the presence of phosphate ought to be chosen.

7. Drug and Vitamin Ok-Dependent Protein (VKDP)

Fusaro et al. carried out a sub-analysis to judge associations between drug consumption and VKDP ranges in 387 haemodialyzed sufferers [62]. The VIKI examine was an observational examine carried out in 387 grownup sufferers of each genders who had been on dialysis for greater than 1 yr at 18 centres in Italy between November 2008 and November 2009. It was designed primarily to evaluate the prevalence of deficiency of vitamin K1 and vitamin K2 in dialysis sufferers. On this sub-study the authors evaluated drug consumption, decided bone Gla proteins (BGP) and MGP ranges, and verified the presence of any vertebral fractures (VF) and VC by backbone radiographs. Concerning mineral and bone dysfunction therapy, the most typical have been oral calcitriol (45.7%) and sevelamer (42.1%).

Whole BGP ranges have been twice as excessive with calcimimetics versus no calcimimetics (290 vs. 158.5 mcg/L, p < 0.0001) and 69% increased with vitamin D analogues (268 vs. 159 mcg/L, p < 0.0001). Whole MGP was 19% increased with calcimimetics (21.5 vs. 18.1 mcg/L, p = 0.04) and 54% increased with calcium acetate (27.9 vs. 18.1 mcg/L, p = 0.003); no distinction was discovered with vitamin D analogues. This discovering of elevated MGP in sufferers handled with calcimimetics is the primary in people and it’s in step with the outcomes of in vitro and in vivo experimental research, during which MGP was measured earlier than and after the administration of the calcimimetic [63,64,65].

Median Whole BGP degree was 29% decrease in sufferers with ≥1 VF (151 vs. 213 mcg/L, p = 0.0091) and 36% decrease in sufferers with VC (164 vs. 262.1 mcg/L, p = 0.0003). In non-survivors, median BGP and MGP have been decrease, however this distinction reached the statistical significance for MGP solely (152 vs. 191 mcg/L, p = 0.20 and 15.0 vs. 19.7 mcg/L, p = 0.02, respectively). No important affiliation between MGP ranges and VF or VC was discovered, regardless of an affiliation between excessive MGP ranges and survival.

Pending research on vitamin Ok supplementation, calcimimetics, and vitamin D analogues might play a job in preserving vitamin Ok-dependent protein exercise, thus contributing to bone and vascular well being in CKD sufferers.

8. Vitamin Ok Supplementation

The query subsequently arises of whether or not CKD sufferers would possibly profit from further vitamin Ok consumption. Within the population-based Rotterdam examine [66], dietary consumption knowledge together with vitamin Ok have been out there for 4800 aged sufferers. The authors assessed the danger of incident coronary coronary heart illness, all-cause mortality, and aortic calcification based mostly on tertiles of energy-adjusted vitamin Ok consumption. They discovered that low vitamin K2 consumption was related to the next incidence of extreme aortic calcification and elevated mortality. In step with this remark, a current pilot examine investigated whether or not day by day vitamin K2 supplementation would enhance the bioactivity of vitamin Ok-dependent proteins in CKD5D sufferers: after solely 6 weeks of day by day vitamin K2 supplementation, a big lower in dp-uc-MGP, ucOC, and uncarboxylated issue II (ucFII) ranges was noticed. This reveals that vitamin Ok is ready to attain tissues, together with the vessel wall, and to right the biochemical and native tissue penalties of vitamin Ok deficiency.

A supplementation in vitamin Ok specifically in HD an PD sufferers ought to be taken under consideration, contemplating the poor vitamin Ok standing in CKD sufferers. One randomized managed trial evaluated the response of biomarkers of vitamin Ok standing (dp-uc-MGP, PIVKA-II and ucOC) to a few doses of vitamin K2 (MK-7) administered over a interval of 6 weeks in HD sufferers and the examine reported that vitamin K2 (MK-7) supplementation decreased dp-uc-MGP and PIVKA-II ranges [11]. Shea et al. reported that supplementation with day by day phylloquinone (0.5 mg) slowed the development of cardiovascular calcification (CAC) over 3 years in wholesome older adults with pre-existing CAC at baseline [67]; it’s effectively established that sufferers with kidney failure have an elevated threat for each vascular calcification and sub-clinical vitamin Ok deficiency however but no trial that examines whether or not vitamin Ok supplementation prevents the development of calcification on this inhabitants has been accomplished.

Moreover, vitamin Ok standing after kidney transplantation might play an vital position. In a examine made by Keyzer et al. [68], vitamin Ok deficiency was an vital threat issue of general mortality in kidney-transplanted sufferers.

Writer Contributions

All Authors contributed in writing and reviewing the article.

Funding

This analysis acquired no exterior funding.

Conflicts of Curiosity

The authors declare no battle of curiosity.

References

1. Shearer M.J., Newman P. Metabolism and cell biology of vitamin Ok. Thromb Haemost. 2008;100:530–547. [PubMed] [Google Scholar]
3. Elder S.J., Haytowitz D.B., Howe J., Peterson J.W., Sales space S.L. Vitamin Ok contents of meat, dairy, and quick meals within the US weight loss plan. J. Agric. Meals Chem. 2006;54:463–467. doi: 10.1021/jf052400h. [PubMed] [CrossRef] [Google Scholar]
4. Sakano T., Nagaoka T., Morimoto A., Hirauchi Ok. Measurement of Ok nutritional vitamins in human and animal feces by high-performance liquid chromatography with fluorometric detection. Chem. Pharm. Bull. 1986;34:4322–4326. doi: 10.1248/cpb.34.4322. [PubMed] [CrossRef] [Google Scholar]
5. Ji Y., Li X., Tso P. Intestinal fatty acid absorption. Immununol. Endocr. Metab. Brokers Med. Chem. 2009;9:60–73. doi: 10.2174/187152209788009832. [CrossRef] [Google Scholar]
6. Fusaro M., Gallieni M., Rizzo M.A., Stucchi A., Delanaye P., Cavalier E., Moysés R.M.A., Jorgetti V., Iervasi G., Giannini S., et al. Vitamin Ok plasma ranges dedication in human well being. Clin. Chem. Lab. Med. 2017;55:789–799. doi: 10.1515/cclm-2016-0783. [PubMed] [CrossRef] [Google Scholar]
7. Fusaro M., Crepaldi G., Maggi S., Galli F., D’Angelo A., Calò L., Giannini S., Miozzo D., Gallieni M. Vitamin Ok, bone fractures, and vascular calcifications in persistent kidney illness: An vital however poorly studied relationship. J. Endocrinol. Investig. 2011;34:317–323. doi: 10.1007/BF03347093. [PubMed] [CrossRef] [Google Scholar]
8. Buranasinsup S., Bunyaratavej N. The intriguing correlation between undercarboxylated osteocalcin and vitamin D. J. Med. Assoc. Thail. 2015;98(Suppl. 8):S16–S20. [PubMed] [Google Scholar]
9. Caluwé R., Vandecasteele S., Van Vlem B., Vermeer C., De Vriese A.S. Vitamin K2 supplementation in haemodialysis sufferers: A randomized dose-finding examine. Nephrol. Dial. Transplant. 2014;29:1385–1390. doi: 10.1093/ndt/gft464. [PubMed] [CrossRef] [Google Scholar]
10. Boxma P.Y., van den Berg E., Geleijnse J.M., Laverman G.D., Schurgers L.J., Vermeer C., Kema I.P., Muskiet F.A., Navis G., Bakker S.J., et al. Vitamin Ok consumption and plasma desphospho-uncarboxylated matrix Gla-protein ranges in kidney transplant recipients. PLoS ONE. 2012;7:e47991. doi: 10.1371/journal.pone.0047991. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
11. Westenfeld R., Krueger T., Schlieper G., Cranenburg E.C., Magdeleyns E.J., Heidenreich S., Holzmann S., Vermeer C., Jahnen-Dechent W., Ketteler M., et al. Impact of vitamin K2 supplementation on purposeful vitamin Ok deficiency in hemodialysis sufferers: A randomized trial. Am. J. Kidney Dis. 2012;59:186–195. doi: 10.1053/j.ajkd.2011.10.041. [PubMed] [CrossRef] [Google Scholar]
12. Cranenburg E.C., Koos R., Schurgers L.J., Magdeleyns E.J., Schoonbrood T.H., Landewé R.B. Characterisation and potential diagnostic worth of circulating matrix Gla protein (MGP) species. Thromb. Haemost. 2010;104:811–822. doi: 10.1160/TH09-11-0786. [PubMed] [CrossRef] [Google Scholar]
13. Delanaye P., Dubois B.E., Lukas P., Peters P., Krzesinski J.M., Pottel H., Cavalier E. Affect of stopping vitamin Ok antagonist remedy on concentrations of dephospho-uncarboxylated Matrix Gla protein. Clin. Chem. Lab. Med. 2015;53:e191-3. doi: 10.1515/cclm-2015-0073. [PubMed] [CrossRef] [Google Scholar]
14. Cranenburg E.C.M., Schurgers L.J., Uiterwijk H.H., Beulens J.W., Dalmeijer G.W., Westerhuis R., Magdeleyns E.J., Herfs M., Vermeer C., Laverman G.D. Vitamin Ok consumption and standing are low in hemodialysis sufferers. Kidney Int. 2012;82:605–610. doi: 10.1038/ki.2012.191. [PubMed] [CrossRef] [Google Scholar]
15. Bellasi A., Raggi P. Vascular imaging in persistent kidney illness. Curr. Opin. Nephrol. Hypertens. 2012;21:382–388. doi: 10.1097/MNH.0b013e328354220c. [PubMed] [CrossRef] [Google Scholar]
16. Schlieper G., Westenfeld R., Krüger T., Cranenburg E.C., Magdeleyns E.J., Brandenburg V.M., Djuric Z., Damjanovic T., Ketteler M., Vermeer C., et al. Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD. J. Am. Soc. Nephrol. 2011;22:387–395. doi: 10.1681/ASN.2010040339. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
17. Shea M.Ok., O’Donnell C.J., Vermeer C., Magdeleyns E.J., Crosier M.D., Gundberg C.M., Ordovas J.M., Kritchevsky S.B., Sales space S.L. Circulating uncarboxylated matrix gla protein is related to vitamin Ok dietary standing, however not coronary artery calcium, in older adults. J. Nutr. 2011;141:1529–1534. doi: 10.3945/jn.111.139634. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
18. Schurgers L.J., Barreto D.V., Barreto F.C., Liabeuf S., Renard C., Magdeleyns E.J., Vermeer C., Choukroun G., Massy Z.A. The circulating inactive type of matrix gla protein is a surrogate marker for vascular calcification in persistent kidney illness: A preliminary report. Clin. J. Am. Soc. Nephrol. 2010;5:568–575. doi: 10.2215/CJN.07081009. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
19. McCabe Ok., Sales space S., Fu X., Shobeiri N., Pang J., Adams M., Holden R. Dietary vitamin Ok and therapeutic warfarin alter the susceptibility to vascular calcification in experimental persistent kidney illness. Kidney Int. 2013;83:835–844. doi: 10.1038/ki.2012.477. [PubMed] [CrossRef] [Google Scholar]
20. Holden R.M., Morton A.R., Garland J.S., Pavlov A., Day A.G., Sales space S.L. Nutritional vitamins Ok and D standing in levels 3–5 persistent kidney illness. Clin. J. Am. Soc. Nephrol. 2010;5:590–597. doi: 10.2215/CJN.06420909. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
22. Voong Ok., Harrington D., Goldsmith D. Vitamin Ok standing in persistent kidney illness: A report of a examine and a mini-review. Int. Urol. Nephrol. 2013;45:1339–1344. doi: 10.1007/s11255-012-0367-x. [PubMed] [CrossRef] [Google Scholar]
23. Stankowiak-Kulpa H., Krzyzanowska P., Koziol L., Grzymislawski M., Wanic-Kossowska M., Moczko J., Walkowiak J. Vitamin Ok standing in peritoneally dialyzed sufferers with persistent kidney illness. Acta Biochim. Pol. 2011;58:617–620. [PubMed] [Google Scholar]
24. Holden R.M., Iliescu E., Morton A.R., Sales space S.L. Vitamin Ok standing of canadian peritoneal dialysis sufferers. Perit. Dial. Int. 2008;28:415–418. [PubMed] [Google Scholar]
25. Jansz T.T., Neradova A., van Ballegooijen A.J., Verhaar M.C., Vervloet M.G., Schurgers L.J., van Jaarsveld B.C. The position of kidney transplantation and phosphate binder use in vitamin Ok standing. PLoS ONE. 2018;13:e0203157. doi: 10.1371/journal.pone.0203157. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
26. Tantisattamo E., Han Ok.H., O’Neill W.C. Elevated vascular calcification in sufferers receiving warfarin. Arterioscler. Thromb. Vasc. Biol. 2015;35:237–242. doi: 10.1161/ATVBAHA.114.304392. [PubMed] [CrossRef] [Google Scholar]
27. Rodriguez-Garcia M., Gomez-Alonso C., Naves-Diaz M., Díaz López J.B., Megido J., Gago E., Forascepi R., Cannata Andía J.B. Prevalence of vertebral fractures and aortic calcifications in hemodialysis sufferers: Comparability with a inhabitants of the identical age and intercourse. Nefrologia. 2003;23(Suppl. 2):106–111. [PubMed] [Google Scholar]
28. Jamal S.A., Gilbert J., Gordon C., Bauer D.C. Cortical pQCT measures are related to fractures in dialysis sufferers. J. Bone Miner. Res. 2006;21:543–548. doi: 10.1359/jbmr.060105. [PubMed] [CrossRef] [Google Scholar]
29. Rodriguez-Garcia M., Gomez-Alonso C., Naves-Diaz M., Diaz-Lopez J.B., Diaz-Corte C., Cannata-Andia J.B., Asturias Research Group Vascular calcifications, vertebral fractures and mortality in haemodialysis sufferers. Nephrol. Dial. Transplant. 2009;24:239–246. doi: 10.1093/ndt/gfn466. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
30. Alem A.M., Sherrard D.J., Gillen D.L., Weiss N.S., Beresford S.A., Heckbert S.R., Wong C., Stehman-Breen C. Elevated threat of hip fracture amongst sufferers with end-stage renal illness. Kidney Int. 2000;58:396–399. doi: 10.1046/j.1523-1755.2000.00178.x. [PubMed] [CrossRef] [Google Scholar]
31. Kohlmeier M., Saupe J., Shearer M.J., Schaefer Ok., Asmus G. Bone well being of grownup hemodialysis sufferers is said to vitamin Ok standing. Kidney Int. 1997;51:1218–1221. doi: 10.1038/ki.1997.166. [PubMed] [CrossRef] [Google Scholar]
32. Fusaro M., Noale M., Viola V., Galli F., Tripepi G., Vajente N., Plebani M., Zaninotto M., Guglielmi G., Miotto D., et al. VItamin Ok Italian (VIKI) dialysis examine investigators. Vitamin Ok, vertebral fractures, vascular calcifications, and mortality: Vitamin Ok Italian (VIKI) dialysis examine. J. Bone Miner. Res. 2012;27:2271–2278. doi: 10.1002/jbmr.1677. [PubMed] [CrossRef] [Google Scholar]
33. Fusaro M., Tripepi G., Noale M., Plebani M., Zaninotto M., Piccoli A., Naso A., Miozzo D., Giannini S., Avolio M., et al. Prevalence of vertebral fractures, vascular calcifications, and mortality in warfarin handled hemodialysis sufferers. Curr. Vasc. Pharmacol. 2013;13:248–258. doi: 10.2174/15701611113119990146. [PubMed] [CrossRef] [Google Scholar]
34. Cockayne S., Adamson J., Lanham-New S., Shearer M.J., Gilbody S., Torgerson D.J. Vitamin Ok and prevention of fractures: Systematic overview and meta-analysis of randomized managed trials. Arch. Intern. Med. 2006;166:1256–1261. doi: 10.1001/archinte.166.12.1256. [PubMed] [CrossRef] [Google Scholar]
35. Schurgers L.J., Aebert H., Vermeer C., Bultmann B., Janzen J. Oral anticoagulant therapy: Pal or foe in heart problems? Blood. 2004;104:3231–3232. doi: 10.1182/blood-2004-04-1277. [PubMed] [CrossRef] [Google Scholar]
36. Koos R., Mahnken A.H., Muhlenbruch G., Brandenburg V., Pflueger B., Wildberger J.E., Kuhl H.P. Relation of oral anticoagulation to cardiac valvular and coronary calcium assessed by multislice spiral computed tomography. Am. J. Cardiol. 2005;96:747–749. doi: 10.1016/j.amjcard.2005.05.014. [PubMed] [CrossRef] [Google Scholar]
37. Hristova M., van Beek C., Schurgers L.J., Lanske B., Danziger J. Quickly progressive extreme vascular calcification sparing the kidney allograft following warfarin initiation. Am. J. Kidney Dis. 2010;56:1158–1162. doi: 10.1053/j.ajkd.2010.06.017. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
38. Rennenberg R.J., van Varik B.J., Schurgers L.J., Hamulyak Ok., Ten Cate H., Leiner T., Vermeer C., de Leeuw P.W., Kroon A.A. Power coumarin therapy is related to elevated extracoronary arterial calcification in people. Blood. 2010;115:5121–5123. doi: 10.1182/blood-2010-01-264598. [PubMed] [CrossRef] [Google Scholar]
39. Weijs B., Blaauw Y., Rennenberg R.J., Schurgers L.J., Timmermans C.C., Pison L., Nieuwlaat R., Hofstra L., Kroon A.A., Wildberger J., et al. Sufferers utilizing vitamin Ok antagonists present elevated ranges of coronary calcification: An observational examine in low-risk atrial fibrillation sufferers. Eur. Coronary heart J. 2011;32:2555–2562. doi: 10.1093/eurheartj/ehr226. [PubMed] [CrossRef] [Google Scholar]
40. Chatrou M.L.L., Winckers Ok., Hackeng T.M., Reutelingsperger C.P., Schurgers L.J. Vascular calcification: The value to pay for anticoagulation remedy with vitamin Ok-antagonists. Blood Rev. 2012;26:155–166. doi: 10.1016/j.blre.2012.03.002. [PubMed] [CrossRef] [Google Scholar]
41. Hayashi M., Takamatsu I., Kanno Y., Yoshida T., Abe T., Sato Y., Japanese Calciphylaxis Research Group A case-control examine of calciphylaxis in Japanese end-stage renal illness sufferers. Nephrol. Dial. Transplant. 2012;27:1580–1584. doi: 10.1093/ndt/gfr658. [PubMed] [CrossRef] [Google Scholar]
42. Nigwekar S.U., Bloch D.B., Nazarian R.M., Vermeer C., Sales space S.L., Xu D., Thadhani R.I., Malhotra R. Vitamin Ok-dependent carboxylation of matrix Gla protein influences the danger of calciphylaxis. J. Am. Soc. Nephrol. 2017;28:1717–1722. doi: 10.1681/ASN.2016060651. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
43. Krueger T., Westenfeld R., Schurgers L., Brandenburg V. Coagulation meets calcification: The vitamin Ok system. Int. J. Artif. Organs. 2009;32:67–74. doi: 10.1177/039139880903200202. [PubMed] [CrossRef] [Google Scholar]
44. Pisoni R.L., Younger E.W., Dykstra D.M., Greenwood R.N., Hecking E., Gillespie B., Wolfe R.A., Goodkin D.A., Held P.J. Vascular entry use in Europe and the US: Outcomes from the DOPPS. Kidney Int. 2002;61:305–316. doi: 10.1046/j.1523-1755.2002.00117.x. [PubMed] [CrossRef] [Google Scholar]
45. Schwab S.J., Harrington J.T., Singh A., Roher R., Shohaib S.A., Perrone R.D., Meyer Ok., Beasley D. Vascular entry for hemodialysis. Kidney Int. 1999;55:2078–2090. doi: 10.1046/j.1523-1755.1999.00409.x. [PubMed] [CrossRef] [Google Scholar]
46. Lemson M.S., Tordoir J.H., Daemen M.J.A.P., Kitslaar P.J.E.H.M. Intimal hyperplasia in vascular grafts. Eur. J. Vasc. Endovasc. Surg. 2000;19:336–350. doi: 10.1053/ejvs.1999.1040. [PubMed] [CrossRef] [Google Scholar]
47. Goodman W.G., Goldin J., Kuizon B.D., Yoon C., Gales B., Sider D., Wang Y., Chung J., Emerick A., Greaser L., et al. Coronary-artery calcification in younger adults with end-stage renal illness who’re present process dialysis. N. Engl. J. Med. 2000;342:1478–1483. doi: 10.1056/NEJM200005183422003. [PubMed] [CrossRef] [Google Scholar]
48. Balci M., Kirkpantur A., Turkvatan A., Mandıroglu S., Ozturk E., Afsar B. Sclerostin as a brand new key participant in arteriovenous fistula calcification. Herz. 2013;40:289–297. doi: 10.1007/s00059-013-3992-y. [PubMed] [CrossRef] [Google Scholar]
49. Diener H.C., Hajjar Ok., Frank B., Perrey M. New anticoagulants for stroke prevention in atrial fibrillation. Herz. 2012;37:370–377. doi: 10.1007/s00059-012-3617-x. [PubMed] [CrossRef] [Google Scholar]
50. Cario-Toumaniantz C., Boularan C., Schurgers L.J., Le Cunff M., Léger J., Loirand G., Pacaud P. Identification of differentially expressed genes in human varicose veins: Involvement of matrix gla protein in extracellular matrix transforming. J. Vasc. Res. 2007;44:444–459. doi: 10.1159/000106189. [PubMed] [CrossRef] [Google Scholar]
51. Zaragatski E., Grommes J., Schurgers L.J., Langer S., Kennes L., Tamm M., Koeppel T.A., Kranz J., Hackhofer T., Arakelyan Ok., et al. Vitamin Ok antagonism aggravates aggravates persistent kidney disease-induced neointimal hyperplasia and calcification in arterialized veins: Position of vitamin Ok tratment? Kidney Int. 2016;89:601–611. doi: 10.1038/ki.2015.298. [PubMed] [CrossRef] [Google Scholar]
52. Connolly S.J., Ezekowitz M.D., Yusuf S., Eikelboom J., Oldgren J., Parekh A., Pogue J., Reilly P.A., Themeles E., Varrone J., et al. Dabigatran versus warfarin in sufferers with atrial fibrillation. N. Engl. J. Med. 2009;361:1139–1151. doi: 10.1056/NEJMoa0905561. [PubMed] [CrossRef] [Google Scholar]
53. Patel M.R., Mahaffey Ok.W., Garg J., Pan G., Singer D.E., Hacke W., Breithardt G., Halperin J.L., Hankey G.J., Piccini J.P., et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N. Engl. J. Med. 2011;365:883–891. doi: 10.1056/NEJMoa1009638. [PubMed] [CrossRef] [Google Scholar]
54. Chan Ok.E., Edelman E.R., Wenger J.B., Thadhani R.I., Maddux F.W. Dabigatran and rivaroxaban use in atrial fibrillation sufferers on hemodialysis. Circulation. 2015;131:972–979. doi: 10.1161/CIRCULATIONAHA.114.014113. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
55. Siontis Ok.C., Zhang X., Eckard A., Bhave N., Schaubel D.E., He Ok., Tilea A., Stack A.G., Balkrishnan R., Yao X., et al. Outcomes Related to Apixaban Use in Finish-Stage Kidney Illness Sufferers with Atrial Fibrillation in the US. Circulation. 2018 doi: 10.1161/CIRCULATIONAHA.118.035418. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
56. Cozzolino M., Mangano M., Magagnoli L., Di Lullo L., Galassi A., Brancaccio D., Bellasi A. Iron-based Phosphate Binders for ESRD Sufferers G Ital Nefrol. Giornale italiano di nefrologia: Organo ufficiale della Societa italiana di nefrologia. 2016;33:27545638. [PubMed] [Google Scholar]
57. Palmer S.C., Gardner S., Tonelli M., Mavridis D., Johnson D.W., Craig J.C., French R., Ruospo M., Strippoli G.F. Phosphate-binding brokers in adults with CKD: A community meta-analysis of randomized trials. Am. J. Kidney Dis. 2016;68:691–702. doi: 10.1053/j.ajkd.2016.05.015. [PubMed] [CrossRef] [Google Scholar]
58. Ohtake T., Kobayashi S., Oka M., Furuya R., Iwagami M., Tsutsumi D., Mochida Y., Maesato Ok., Ishioka Ok., Moriya H., et al. Lanthanum carbonate delays development of coronary artery calcification in contrast with calcium-based phosphate binders in sufferers on hemodialysis: A pilot examine. J. Cardiovasc. Pharmacol. Ther. 2013;18:439–446. doi: 10.1177/1074248413486355. [PubMed] [CrossRef] [Google Scholar]
59. Raggi P., Bommer J., Chertow G.M. Valvular calcification in hemodialysis sufferers randomized to calcium-based phosphorus binders or sevelamer. J. Coronary heart Valve Dis. 2004;13:134–141. [PubMed] [Google Scholar]
60. Chertow G.M., Burke S.Ok., Raggi P., Deal with to Aim Working Group Sevelamer attenuates the development of coronary and aortic calcification in hemodialysis sufferers. Kidney Int. 2002;62:245–252. doi: 10.1046/j.1523-1755.2002.00434.x. [PubMed] [CrossRef] [Google Scholar]
61. Neradova A., Schumacher S.P., Hubeek I., Lux P., Schurgers L.J., Vervloet M.G. Phosphate binders have an effect on vitamin Ok focus by undesired binding, an in vitro examine. BMC Nephrol. 2017;18:149. doi: 10.1186/s12882-017-0560-3. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
62. Fusaro M., Giannini S., Gallieni M., Noale M., Tripepi G., Rossini M., Messa P., Rigotti P., Pati T., Barbisoni F., et al. Calcimimetic and vitamin D analog use in hemodialyzed sufferers is related to increasedlevels of vitamin Ok dependent proteins. Endocrine. 2016;51:333–341. doi: 10.1007/s12020-015-0673-z. [PubMed] [CrossRef] [Google Scholar]
63. Rodriguez M., Aguilera-Tejero E., Mendoza F.J., Guerrero F., López I. Results of calcimimetics on extraskeletal calcifications in persistent kidney illness. Kidney Int. 2008;74(Suppl. 111):S50–S54. doi: 10.1038/ki.2008.546. [PubMed] [CrossRef] [Google Scholar]
64. Mendoza F.J., Martinez-Moreno J., Almaden Y., Rodriguez-Ortiz M.E., Lopez I., Estepa J.C., Henley C., Rodriguez M., Aguilera-Tejero E. Impact of calcium and the calcimimetic AMG 641 on matrix-GIa protein in vascular easy musclecells. Calcif. Tissue Int. 2011;88:169–178. doi: 10.1007/s00223-010-9442-4. [PubMed] [CrossRef] [Google Scholar]
65. Torbergsen A.C., Watne L.O., Wyller T.B., Frihagen F., Strømsøe Ok., Bøhmer T., Mowe M. Vitamin K1 and 25(OH)D are independently and synergistically related to a threat for hipfracture in an aged inhabitants: A case management examine. Clin. Nutr. 2015;34:101–106. doi: 10.1016/j.clnu.2014.01.016. [PubMed] [CrossRef] [Google Scholar]
66. Geleijnse J.M., Vermeer C., Grobbee D.E., Schurgers L.J., Knapen M.H., van der Meer I.M., Hofman A., Witteman J.C. Dietary consumption of menaquinone is related to a lowered threat of coronary coronary heart illness: The Rotterdam Research. J. Nutr. 2004;134:3100–3105. doi: 10.1093/jn/134.11.3100. [PubMed] [CrossRef] [Google Scholar]
67. Shea M.Ok., O’Donnell C.J., Hoffmann U., Dallal G.E., Dawson-Hughes B., Ordovas J.M., Value P.A., Williamson M.Ok., Sales space S.L. Vitamin Ok supplementation and development of coronary artery calcium in older women and men. Am. J. Clin. Nutr. 2009;89:1799–1807. doi: 10.3945/ajcn.2008.27338. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
68. Keyzer C.A., Vermeer C., Joosten M.M., Knapen M.H., Drummen N.E., Navis G., Bakker S.J., de Borst M.H. Vitamin Ok standing and mortality after kidney transplantation: A cohort examine. Am. J. Kidney Dis. 2015;65:474–483. doi: 10.1053/j.ajkd.2014.09.014. [PubMed] [CrossRef] [Google Scholar]

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