Variation of Phylioquinone (Vitamin K1) Concentrations in Hemodialysis Patients

Kohlmeier, Martin; Saupe, Jörg; Drossel, Hans-Joachim; Shearer, Martin J.

doi:10.1055/s-0038-1649921

Cited by 40 publications

(15 citation statements)

References 12 publications

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“…7,[9][10][11][12] These findings were independent of CYP2C9 polymorphisms, the VKORC1 1173C/T variant, and numerous other factors that can alter warfarin dose requirements. The results were statistically significant among African Americans but not Caucasians; however, the e4 allele was less common among Caucasians, which could have limited our ability to detect an effect in this group.…”

Section: Discussionmentioning

confidence: 76%

“…Sconce et al 16 found that the e4 allele was associated with lower doses in a Caucasian population, but, interestingly, e4 carriers had the highest plasma vitamin K concentrations, not the lowest as might be expected. [10][11][12] Clearly, the relationship between APOE genotype and warfarin dose requirements is complex; further study is needed to better understand the interactions between APOE and race, other genotypes, diet and vitamin K levels. In a retrospective study of different anticoagulants, acenocoumarol and phenprocoumon, Dutch Caucasian e4 carriers and homozygotes required a significantly lower mean dose of acenocoumarol, but not of phenprocoumon, relative to e3/e3 homozygotes.…”

Section: Discussionmentioning

confidence: 99%

“…8 Each isoform varies in its ability to facilitate clearance of vitamin-K-rich lipoproteins from plasma, with e4 having the greatest clearance. [9][10][11][12] Plasma vitamin K levels also vary by APOE genotype, with the highest levels among e2 allele carriers and the lowest in e4 carriers. [10][11][12] Accordingly, some investigators have proposed that the lower plasma levels of vitamin K in e4 carriers lead to lower anticoagulant requirements, 13 whereas others have suggested that the greater uptake of vitamin K into the liver leads to increased availability of vitamin K for coagulation proteins and thus a higher anticoagulant drug requirement to achieve adequate anticoagulation in e4 carriers.…”

Section: Introductionmentioning

confidence: 99%

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Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans

et al. 2007

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Warfarin sodium is a vitamin K antagonist that is plagued by large variability in patient response, including higher dose requirements among African Americans. Polymorphisms in the gene encoding apolipoprotein E (APOE) may partly explain this variability by altering transport of vitamin K to the liver. In a prospective cohort study of 232 individuals (52.2% Caucasian and 47.8% African American) initiating warfarin therapy, the weekly maintenance dose was significantly higher for African Americans than for Caucasians (mean 42.9 versus mean 36.9 mg, P=0.018), and the epsilon4 allele was more common among African Americans (37.8 versus 26.4% for Caucasians). In multivariable analyses, the presence of the epsilon4 allele was associated with a statistically significantly higher warfarin dose among African Americans (median 45.0 mg in epsilon4 carriers versus 35.0 mg in non-epsilon4 carriers, P=0.014) but not Caucasians (38.1 versus 35.0 mg, P=0.60). In addition, warfarin maintenance dose increased among African Americans according to genotype previously associated with differential hepatic chylomicron clearance (epsilon2/epsilon2 or epsilon2/epsilon3: 30.0 mg; epsilon3/epsilon3: 35.0 mg; epsilon3/epsilon4 or epsilon4/epsilon4: 45.0 mg; P=0.012), although the epsilon4/epsilon4 genotype was rare and not clearly associated with higher doses. The association of APOE with warfarin dosing was independent of CYP2C9 and VKORC1 polymorphisms. APOE polymorphisms thus may be important determinants of warfarin maintenance dose and could explain at least some of the observed racial differences in dose requirements.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans

et al. 2007

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“…Additionally, it has been suggested that vitamin K status in hemodialysis patients is also influenced by the apolipoprotein E genotype. Lipoprotein-bound apolipoprotein E regulates the clearance of circulating vitamin K in the liver and in peripheral tissues (33). It is interesting to note that the vitamin K requirement in extrahepatic tissues (for ␥-glutamyl carboxylation of MGP, for example) appears to be greater than that for the liver itself (for the modification of coagulation factors).…”

Section: Discussionmentioning

confidence: 99%

The Circulating Inactive Form of Matrix Gla Protein Is a Surrogate Marker for Vascular Calcification in Chronic Kidney Disease

Schurgers¹,

Barreto²,

Barreto³

et al. 2010

Clinical Journal of the American Society of Nephrology

266

245

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Background and objectives: Vitamin K-dependent matrix Gla protein (MGP) acts as a calcification inhibitor in vitro and in vivo. The present study was performed to (1) determine plasma levels of the inactive, dephosphorylated, uncarboxylated MGP (dp-ucMGP) in a cohort of patients at different stages of chronic kidney disease (CKD) and (2) evaluate the association between dp-ucMGP levels on one hand and aortic calcification and mortality on the other.Design, setting, participants, & measurements: 107 patients (67 ؎ 13 years; 60% male; 32% at CKD stages 2 to 3, 31% at stages 4 to 5, 37% at stage 5D) were assayed for dp-ucMGP and underwent multislice spiral computed tomography scans to quantify aortic calcification at baseline. They were prospectively monitored for mortality.Results: Plasma dp-ucMGP levels augmented progressively with CKD stage, with a significant difference from CKD stage 4. CKD stage, hemoglobin, age, and coumarin use were independently associated with plasma dp-ucMGP levels. Furthermore, plasma dp-ucMGP and age were positively and independently associated with the aortic calcification score. During follow-up (802 ؎ 311 days), 34 patients died (20 from cardiovascular events). In a crude analysis, [plasma dp-ucMGP] > 921 pM was associated with overall mortality; this association was lost after adjusting for both age and the calculated propensity score.Conclusions: Plasma dp-ucMGP increased progressively in a CKD setting and was associated with the severity of aortic calcification. Plasma dp-ucMGP could thus be a surrogate marker for vascular calcification in CKD.Clin J Am Soc Nephrol 5: 568 -575, 2010. doi: 10.2215/CJN.07081009 C ardiovascular diseases account for 50% of all deaths in a chronic kidney disease (CKD) setting (1). Vascular calcification (VC) in the media-intimal arterial layers contributes significantly to the greater mortality in this population (2,3). In fact, it has been repeatedly demonstrated that patients suffering from advanced CKD present VC to a greater extent than individuals with normal renal function (4 -7). Although many factors may influence the occurrence and progression of this condition, the fact that 20% to 40% of the patients in most CKD cohorts (8 -10) do not develop detectable VC (despite exposure to well-known environmental triggers, such as uremia, diabetes, and hyperphosphatemia) suggests that naturally occurring VC inhibitors have an important role in preventing this disease process.Matrix Gla protein (MGP) is a 10-kD protein secreted by chondrocytes and vascular smooth muscle cells in the arterial media (11). It is the first protein known to act as a calcification inhibitor in vivo (12)(13)(14), probably by directly inhibiting calcium precipitation and crystallization in the vessel wall (15) and antagonizing bone morphogenetic protein-2 (which regulates osteoblast differentiation, and thus bone formation (16)). In particular, MGP only exerts its anticalcification activity after posttranslational ␥-glutamyl carboxylation of five glutamate residues-a crucial ac...

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“…This intestinal absorption involves the solubilization of vitamin K into mixed micelles composed of bile salts and products of pancreatic lipolysis and is known to be impaired in patients with malabsorption or other gastrointestinal disorders, including biliary atresia, cystic fibrosis, celiac disease, and short bowel syndrome [12]. Vitamin K is not known to have a carrier protein; instead, triglyceride-rich lipoproteins (TRL), primarily chylomicron remnants and very low-density lipoproteins (VLDL), are thought to be the main transporters of phylloquinone [13][14][15]. Vitamin K is extensively metabolized in the liver and excreted in the urine (20%) and bile (40%).…”

Section: Introductionmentioning

confidence: 99%

A Validated HPLC Method for the Determination of Vitamin K in Human Serum – First Application in a Pharmacological Study

Marinova¹,

Lütjohann

Westhofen³

et al. 2011

TOCCHEMJ

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Dietary phylloquinone (vitamin K1) is considered to be a major determinant of human vitamin K status. For this reason, measurements of plasma vitamin K concentrations provide a useful tool of vitamin K status in man. There is a growing interest in the role, biochemical function, and metabolism of vitamin K in vivo.A modified reversed phase-HPLC method with fluorescence detection after post-column zinc reduction in serum samples was validated for vitamin K analysis. Two human volunteers were investigated after p.o. and i.v. administration of 2 mg Konakion ® MM. Blood samples were collected periodically after administration and subjected to pharmacokinetic evaluation.High sensitivity, analytical recoveries, accuracy and calibration curves linearities could be reached. Our results showed an overall coefficient of variation of less than 10% for the intra-and interday reproducibility, while the recovery ranged from 91% to 114 %. The limit of detection and quantification were 0.015 ng mL -1 and 0.15 ng mL -1 , respectively. Long-term stability was verified over a period of six months. The accuracy was proven by good results from external quality assurance.The observed pharmacokinetic differences indicate significant intra-and inter-individual variance of vitamin K fate in the human body.This highly accurate, robust and reliable method is appropriate for the evaluation of vitamin K status in human serum. The ability to determine vitamin K has the potential to improve pharmacokinetic studies.

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Variation of Phylioquinone (Vitamin K1) Concentrations in Hemodialysis Patients

Cited by 40 publications

References 12 publications

Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans

Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans

The Circulating Inactive Form of Matrix Gla Protein Is a Surrogate Marker for Vascular Calcification in Chronic Kidney Disease

A Validated HPLC Method for the Determination of Vitamin K in Human Serum – First Application in a Pharmacological Study

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