RESUMO
Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r2 ≤ 0.26) and distinct distribution pattern in renal and non-renal patients. In conclusion, VKA use exacerbated vitamin K deficiency across all etiologies, while vitamin K supplementation resulted in a vascular VKDP status better than that of the general population. Weak correlation of vitamin K biomarkers calls for thoughtful selection lead by the research question. Vitamin K status in non-renal deficient patients was not anomalous and may question the role of vitamin K deficiency in the pathogenesis of VC in these patients.
Assuntos
Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/sangue , Proteínas da Matriz Extracelular/sangue , Precursores de Proteínas/sangue , Calcificação Vascular/sangue , Deficiência de Vitamina K/sangue , Vitamina K/sangue , 4-Hidroxicumarinas/uso terapêutico , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/complicações , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Suplementos Nutricionais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Indenos/uso terapêutico , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Protrombina , Diálise Renal/efeitos adversos , Uremia/sangue , Uremia/complicações , Calcificação Vascular/complicações , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico , Deficiência de Vitamina K/complicações , Proteína de Matriz GlaRESUMO
BACKGROUND: Patients with CKD are at an increased risk of developing vascular calcification (VC) and bone complications which translate into a higher morbidity and mortality. The dephosphorylated and uncarboxylated matrix Gla protein (dp-ucMGP) is considered to be an indicator of vitamin K2 status and correlates with markers of VC. It is activated by γ-glutamyl carboxylase that converts inactive MGP into an active form, and vitamin K2 is a cofactor of this reaction. The active form of MGP is a known inhibitor of arterial wall calcification and plays an important role in bone turnover. Recent studies show poor vitamin K2 status in CKD patients. We aimed to review the literature for the association between vitamin K2 status and calcification and bone disease risk and the efficacy of vitamin K2 supplementation in CKD population. SUMMARY: Most CKD patients, including those on renal replacement therapy, have vitamin K2 deficiency. The dp-ucMGP level, a marker of vitamin K2 status, is decreased by vitamin K2 supplementation in CKD patients, but there is no unequivocal proof that it influences arterial calcification progression and bone complications. Key Messages: CKD population are at risk of vitamin K deficiency. Supplementation of vitamin K2 is safe and improves the serum markers of its deficiency. There is lack of strong evidence that vitamin K2 supplementation slows progression of calcification or reduces the frequency of bone complications. More prospective studies are needed.
Assuntos
Insuficiência Renal Crônica/sangue , Vitamina K 2/uso terapêutico , Deficiência de Vitamina K/sangue , Animais , Doenças Ósseas/sangue , Doenças Ósseas/etiologia , Doenças Ósseas/prevenção & controle , Suplementos Nutricionais , Humanos , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Calcificação Vascular/sangue , Calcificação Vascular/etiologia , Calcificação Vascular/prevenção & controle , Vitamina K 2/sangue , Deficiência de Vitamina K/complicações , Deficiência de Vitamina K/tratamento farmacológicoRESUMO
We report a probable case of abetalipoproteinemia in an infant who presented with unusual symptoms of late-onset vitamin K deficiency. Abetalipoproteinemia is a rare autosomal recessive disease caused by mutation of the microsomal triglyceride transfer protein gene, resulting in the absence of microsomal triglyceride transfer protein function in the small bowel. It is characterized by the absence of plasma apolipoprotein B-containing lipoproteins, fat malabsorption, hypocholesterolemia, retinitis pigmentosa, progressive neuropathy, myopathy, and acanthocytosis. A biopsy of the small intestine characteristically shows marked lipid accumulation in the villi of enterocytes. Large supplements of fat-soluble vitamins A, D, E, and K have been shown to limit neurologic and ocular manifestations. Dietary fat intake is limited to medium-chain triglycerides.
Assuntos
Abetalipoproteinemia/complicações , Deficiência de Vitamina K/complicações , Abetalipoproteinemia/sangue , Abetalipoproteinemia/diagnóstico , Abetalipoproteinemia/patologia , Duodeno/patologia , Enterócitos/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/diagnóstico , Deficiência de Vitamina K/patologiaRESUMO
OBJECTIVES: We aimed to determine serum 25-hydroxyvitamin D (25(OH)D) and undercarboxylated osteocalcin (ucOC) levels in severe motor and intellectual disabilities (SMID) patients and their association with bone turnover biomarkers. METHODS: We assessed vitamin D and K levels as indicators of osteoporosis in institutionalized adults with SMID. From December 2019 to February 2020, 93 institutionalized patients (48 men, 45 women; median age, 49 years) underwent annual routine examinations. Serum ucOC, 25(OH)D, bone-specific alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase A 5b (TRACP-5b) levels as bone formation and resorption markers and calcium and phosphorous levels were measured. Vitamin K deficiency was indirectly assessed based on ucOC levels. RESULTS: Mean ucOC levels were higher than normal (i.e., vitamin K deficiency). Serum 25(OH)D levels were markedly diminished. Overall, 86% of patients had deficient 25(OH)D levels. These 25(OH)D-deficient patients had higher ucOC levels. Multiple linear regression analysis revealed an inverse correlation between 25(OH)D and ucOC levels. ucOC levels were significantly higher and 25(OH)D levels were significantly lower in tube feeding. TRACP-5b levels were significantly higher in elderly than in young women. BAP and TRACP-5b levels were normal in adults. No relationship existed between vitamin D and antiepileptic drug use. CONCLUSIONS: Vitamin K and D co-deficiency was common in SMID patients. Vitamin K and D deficiencies were worse in tube-fed patients than in oral intake patients. SMID patients should undergo regular monitoring of vitamin D and K levels and supplementation of these vitamins.
Assuntos
Deficiência Intelectual/fisiopatologia , Transtornos das Habilidades Motoras/fisiopatologia , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina K/epidemiologia , Adulto , Idoso , Biomarcadores/sangue , Densidade Óssea , Feminino , Humanos , Institucionalização , Deficiência Intelectual/metabolismo , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Transtornos das Habilidades Motoras/metabolismo , Osteocalcina/sangue , Osteoporose/complicações , Pessoas com Deficiência Mental , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Vitamina K/metabolismo , Deficiência de Vitamina K/sangue , VitaminasRESUMO
Patients with intestinal fat malabsorption and urolithiasis are particularly at risk of acquiring fat-soluble vitamin deficiencies. The aim of the study was to evaluate the vitamin status and metabolic profile before and after the supplementation of fat-soluble vitamins A, D, E and K (ADEK) in 51 patients with fat malabsorption due to different intestinal diseases both with and without urolithiasis. Anthropometric, clinical, blood and 24-h urinary parameters and dietary intake were assessed at baseline and after ADEK supplementation for two weeks. At baseline, serum aspartate aminotransferase (AST) activity was higher in stone formers (SF; n = 10) than in non-stone formers (NSF; n = 41) but decreased significantly in SF patients after supplementation. Plasma vitamin D and E concentrations increased significantly and to a similar extent in both groups during intervention. While plasma vitamin D concentrations did not differ between the groups, vitamin E concentrations were significantly lower in the SF group than the NSF group before and after ADEK supplementation. Although vitamin D concentration increased significantly in both groups, urinary calcium excretion was not affected by ADEK supplementation. The decline in plasma AST activity in patients with urolithiasis might be attributed to the supplementation of ADEK. Patients with fat malabsorption may benefit from the supplementation of fat-soluble vitamins ADEK.
Assuntos
Síndromes de Malabsorção/sangue , Urolitíase/sangue , Vitamina A/sangue , Vitamina D/sangue , Vitamina E/sangue , Vitamina K/sangue , Adulto , Idoso , Aspartato Aminotransferases/sangue , Colesterol/sangue , Suplementos Nutricionais , Feminino , Humanos , Síndromes de Malabsorção/complicações , Síndromes de Malabsorção/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Triglicerídeos/sangue , Urolitíase/complicações , Urolitíase/terapia , Vitamina A/administração & dosagem , Deficiência de Vitamina A/sangue , Deficiência de Vitamina A/etiologia , Deficiência de Vitamina A/terapia , Vitamina D/administração & dosagem , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/terapia , Vitamina E/administração & dosagem , Deficiência de Vitamina E/sangue , Deficiência de Vitamina E/etiologia , Deficiência de Vitamina E/terapia , Vitamina K/administração & dosagem , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/etiologia , Deficiência de Vitamina K/terapia , Vitaminas/administração & dosagem , Vitaminas/sangueRESUMO
BACKGROUND: A low vitamin D and K status has been associated with increased cardiovascular disease (CVD) risk but the evidence of their combined effect on cardiovascular health is limited. OBJECTIVES: Our study aimed to investigate the prospective association of vitamin D and K status with subclinical measures of cardiovascular health and all-cause mortality among a population of Dutch Caucasians. METHODS: We performed an observational prospective study on 601 participants of the Hoorn Study (mean ± SD age: 70 ± 6 y, 50.4% women, BMI: 27.2 ± 4.0 kg/m2), of whom 321 underwent an echocardiogram in 2000-2001 and 2007-2009. Vitamin D and K status was assessed at baseline by serum 25-hydroxyvitamin D [25(OH)D] and plasma desphospho-uncarboxylated matrix-gla protein (dp-ucMGP)-high concentrations indicate low vitamin K status. Vital status was assessed from baseline until 2018. We studied the association of categories of 25(OH)D (stratified by the clinical cutoff of 50 mmol/L) and dp-ucMGP (stratified by the median value of 568 pmol/L) with echocardiographic measures using linear regression and with all-cause mortality using Cox regression, adjusted for confounders. RESULTS: Compared with markers of normal vitamin D and K status, markers of low vitamin D and K status were prospectively associated with increased left ventricular mass index (5.9 g/m2.7; 95% CI: 1.8, 10.0 g/m2.7). Participants with low vitamin D and K status were also at increased risk of all-cause mortality with an HR of 1.64 (95% CI: 1.12, 2.39) compared with normal vitamin D and K status. CONCLUSIONS: A combination of low vitamin D and K status is associated with adverse cardiac remodeling and increased risk of all-cause mortality in men and women. Future studies should investigate whether vitamin D and K supplementation could help to improve cardiovascular health and to decrease CVD risk.
Assuntos
Doenças Cardiovasculares , Mortalidade , Vitamina D/sangue , Vitamina K/sangue , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Deficiência de Vitamina D/sangue , Deficiência de Vitamina K/sangueRESUMO
We have previously reported that patients with severe motor and intellectual disabilities (SMID) have a high prevalence of vitamin K deficiency both in the liver and bone. Thus, vitamin K therapy for SMID patients should be considered. In the present study, we have studied the efficacy of nutritional therapy with vitamin K1 for improving their vitamin K status and bone metabolism markers in patients with SMID. During the 3-mo period, 19 patients under enteral feeding received vitamin K1 treatment, the dose of which was determined to meet each subject's energy requirement. Biomarkers of vitamin K insufficiency; protein induced by vitamin K absence or antagonist-II (PIVKA-II), undercarboxylated osteocalcin (ucOC), intact osteocalcin (intact OC) and bone turnover markers (tartrate-resistant acid phosphatase-5b: TRACP-5b and bone alkaline phosphatase: BAP) were measured at baseline and post treatment. The ucOC/OC ratio was calculated as a more sensitive index than ucOC for vitamin K status in the bone. After treatment, the median vitamin K intake increased from 66 to 183 µg/d, and serum levels of PIVKA-II and ucOC/OC ratio were significantly decreased. Decrements of serum ucOC level and ucOC/OC ratio were significantly associated with vitamin K intake, indicating that both markers well reflect the dose-dependent vitamin K effects. Serum levels of BAP and TRACP-5b were significantly increased after vitamin K1 therapy. Nutritional therapy with vitamin K1 effectively improved the markers for vitamin K status and bone turnover, and was considered to be a good candidate for treatment in SMID patients.
Assuntos
Remodelação Óssea , Osso e Ossos/metabolismo , Deficiência Intelectual/complicações , Transtornos Motores/complicações , Vitamina K 1/uso terapêutico , Deficiência de Vitamina K/tratamento farmacológico , Adulto , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Pessoas com Deficiência , Feminino , Humanos , Deficiência Intelectual/sangue , Pessoa de Meia-Idade , Transtornos Motores/sangue , Terapia Nutricional , Necessidades Nutricionais , Estado Nutricional , Osteocalcina/sangue , Precursores de Proteínas/sangue , Protrombina , Índice de Gravidade de Doença , Fosfatase Ácida Resistente a Tartarato/sangue , Resultado do Tratamento , Vitamina K 1/sangue , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/etiologia , Adulto JovemRESUMO
Vitamin K is a composite term referring to a group of fat-soluble vitamins that function as a cofactor for the enzyme γ-glutamyl carboxylase (GGCX), which activates a number of vitamin K-dependent proteins (VKDPs) involved in haemostasis and vascular and bone health. Accumulating evidence demonstrates that chronic kidney disease (CKD) patients suffer from subclinical vitamin K deficiency, suggesting that this represents a population at risk for the biological consequences of poor vitamin K status. This deficiency might be caused by exhaustion of vitamin K due to its high requirements by vitamin K-dependent proteins to inhibit calcification.
Assuntos
Insuficiência Renal Crônica/tratamento farmacológico , Deficiência de Vitamina K/tratamento farmacológico , Vitamina K/sangue , Vitamina K/farmacologia , Osso e Ossos/metabolismo , Carbono-Carbono Ligases/metabolismo , Suplementos Nutricionais , Humanos , Estado Nutricional , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/sangue , Deficiência de Vitamina K/sangue , Varfarina/administração & dosagem , Varfarina/efeitos adversosRESUMO
Vascular calcification is a critical complication in patients with chronic kidney disease (CKD) because it is predictive of cardiovascular events and mortality. In addition to the traditional mechanisms associated with endothelial dysfunction and the osteoblastic transformation of vascular smooth muscle cells (VSMCs), the regulation of calcification inhibitors, such as calciprotein particles (CPPs) and matrix vesicles plays a vital role in uremic vascular calcification in CKD patients because of the high prevalence of vitamin K deficiency. Vitamin K governs the gamma-carboxylation of matrix Gla protein (MGP) for inhibiting vascular calcification, and the vitamin D binding protein receptor is related to vitamin K gene expression. For patients with chronic kidney disease, adequate use of vitamin D supplements may play a role in vascular calcification through modulation of the calciprotein particles and matrix vesicles (MVs).
Assuntos
Insuficiência Renal Crônica/tratamento farmacológico , Calcificação Vascular/tratamento farmacológico , Vitamina D/farmacologia , Vitamina K/farmacologia , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Suplementos Nutricionais , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Humanos , Hiperfosfatemia/sangue , Hiperfosfatemia/tratamento farmacológico , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Calcificação Vascular/sangue , Calcificação Vascular/etiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/tratamento farmacológico , Proteína de Matriz GlaRESUMO
The associations of multiple vitamin deficiencies on incident fractures were uncertain, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women. The number of deficiencies was additively associated with incident fracture after adjustment for possible confounding factors including the treatment of osteoporosis. INTRODUCTION: To evaluate the associations of multiple vitamin deficiencies on incident fractures, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women. METHODS: This analysis used a subset of the ongoing cohort maintained by a primary care institution. Inclusion criteria of the present study were postmenopausal women aged ≥ 50 years, without vitamin supplementation and secondary osteoporosis. Baseline serum concentrations of 25-hydroxyvitamin D (25(OH)D), undercarboxylated osteocalcin (ucOC), and homocysteine (Hcy) were measured to assess vitamin D, vitamin K, and vitamin B, respectively. Since 25(OH) D positively relates to vitamin D, ucOC and Hcy negatively relate to vitamin K and vitamin B nutrients, respectively, the subjects with lower (25(OH)D) or higher (ucOC or Hcy) values than each median value was defined as subjects with the corresponding vitamin deficiency. Subjects were divided into four groups according to the number of deficiency: no deficiency, single deficiency, double deficiencies, and triple deficiencies. Relationships between the vitamin deficiencies and incident fractures were evaluated by Cox regression analysis. RESULTS: A total of 889 subjects were included in this analysis; their mean and SD age was 68.3 ± 9.5 years, and the follow-up period was 6.3 ± 5.1 years. The numbers of subjects in the four groups were 139 (15.6%), 304 (34.2%), 316 (35.5%), and 130 (14.6%) for the groups with no, single, double, and triple deficiencies, respectively. Incident fractures were observed in 264 subjects (29.7%) during the observation period. The number of deficiencies was significantly associated with incident fracture (hazard ratio 1.25, 95% confidence interval 1.04-1.50, P = 0.018) after adjustment for possible confounding factors including the treatment of osteoporosis. CONCLUSION: Accumulation of vitamin deficiencies was related to incident fractures.
Assuntos
Deficiência de Vitaminas/complicações , Osteoporose Pós-Menopausa/etiologia , Fraturas por Osteoporose/etiologia , Absorciometria de Fóton/métodos , Idoso , Deficiência de Vitaminas/sangue , Deficiência de Vitaminas/epidemiologia , Densidade Óssea/fisiologia , Feminino , Homocisteína/sangue , Humanos , Incidência , Japão/epidemiologia , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/epidemiologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/epidemiologia , Fatores de Risco , Deficiência de Vitaminas do Complexo B/sangue , Deficiência de Vitaminas do Complexo B/complicações , Deficiência de Vitaminas do Complexo B/epidemiologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/complicações , Deficiência de Vitamina K/epidemiologiaRESUMO
We present here a late preterm infant with extensive brain lesions resulting from vitamin K deficiency. A female infant was born after 35 weeks of gestation by emergent cesarean section because of non-reassuring fetal status. Her mother had severe eating disorder and recurrent vomiting since early pregnancy. She was immediately intubated and ventilated because she was extremely pale, hypotonic, and non-reactive. Cerebral magnetic resonance imaging immediately after birth showed intraparenchymal hemorrhage in the left frontal lobe and cerebellum, marked cerebral edema, and cerebellar hypoplasia. Coagulation studies of the infant showed hepaplastin test <5%, prolonged PT and APTT, and a marked elevation of protein induced by vitamin K absence or antagonist-II. This case highlighted a potential risk of intracranial bleeding due to maternal vitamin K deficiency and difficulty in its prediction before delivery. Vitamin K supplementation to high risk mothers might be indispensable for preventing severe fetal vitamin K deficiency. Even when coagulation studies in mothers is normal, it is imperative to provide vitamin K supplementation for total protection.
Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Hemorragias Intracranianas/etiologia , Mães , Complicações Hematológicas na Gravidez/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Deficiência de Vitamina K/complicações , Vitamina K/uso terapêutico , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/sangue , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Feminino , Humanos , Recém-Nascido , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/diagnóstico por imagem , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Complicações Hematológicas na Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Resultado do Tratamento , Deficiência de Vitamina K/sangue , Vômito/complicaçõesRESUMO
BACKGROUND: Matrix Gla protein (MGP) is an extrahepatic protein that is dependent on glutamate carboxylation, a vitamin K-dependent process. Its dysfunctional form, desphospho-uncarboxylated-MGP, has been associated with increased arterial calcification and stiffness. The aim of this study was to measure the degree of postoperative carboxylation of MGP and two other Gla proteins in patients scheduled for abdominal or orthopaedic surgery. METHODS: Forty patients undergoing abdominal or orthopaedic surgery were included. Blood samples were collected preoperatively and four days after the surgery. Desphospho-carboxylated MGP (dp-cMGP), desphospho-uncarboxylated MGP (dp-ucMGP), carboxylated osteocalcin (OC) (cOC), uncarboxylated OC (ucOC), and uncarboxylated prothrombin (PIVKA-II) were analysed. RESULTS: Preoperatively, 29 patients had dp-ucMGP levels above the reference values. Patients with pre-existing cardiovascular comorbidities had higher dp-ucMGP preoperatively compared with patients with no record of cardiovascular disease. Postoperatively, this number increased to 36 patients, and median dp-ucMGP levels increased (p < 0.0001) and correlated to a PIVKA-II increase (r = 0.44). On the other hand, dp-cMGP levels did not significantly alter. Decreased levels of ucOC and cOC were seen after surgery (p = 0.017 and p = 0.0033, respectively). Comorbidities, possible nutritional defects, and complications affecting Gla protein activity and function were identified. CONCLUSIONS: Dp-ucMGP was high preoperatively, and had further increased postoperatively. This pattern was linked to several comorbidities, possible nutritional defects, and postoperative complications, which motivates further research about potential interactions between perioperative corrective treatments with vitamin K supplements, cardiovascular biomarkers, and incidents of stroke and myocardial infarction events.
Assuntos
Abdome/cirurgia , Proteínas de Ligação ao Cálcio/sangue , Doenças Cardiovasculares/etiologia , Proteínas da Matriz Extracelular/sangue , Procedimentos Ortopédicos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Osteocalcina/sangue , Fosforilação , Estudos Prospectivos , Precursores de Proteínas/sangue , Protrombina , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/diagnóstico , Deficiência de Vitamina K/etiologia , Proteína de Matriz GlaRESUMO
INTRODUCTION: Zellweger spectrum disorders (ZSDs) are caused by an impairment of peroxisome biogenesis, resulting in multiple metabolic abnormalities. This leads to a range of symptoms, including hepatic dysfunction and coagulopathy. This study evaluated the incidence and severity of coagulopathy and the effect of vitamin K supplementation orally and IV in ZSD. METHODS: Data were retrospectively retrieved from the medical records of 30 ZSD patients to study coagulopathy and the effect of vitamin K orally on proteins induced by vitamin K absence (PIVKA-II) levels. Five patients from the cohort with a prolonged prothrombin time, low factor VII, and elevated PIVKA-II levels received 10 mg of vitamin K IV. Laboratory results, including thrombin generation, at baseline and 72 h after vitamin K administration were examined. RESULTS: In the retrospective cohort, four patients (13.3%) experienced intracranial bleedings and 14 (46.7%) reported minor bleeding. No thrombotic events occurred. PIVKA-II levels decreased 38% after start of vitamin K therapy orally. In the five patients with a coagulopathy, despite treatment with oral administration of vitamin K, vitamin K IV caused an additional decrease (23%) of PIVKA-II levels and increased thrombin generation. CONCLUSION: Bleeding complications frequently occur in ZSD patients due to liver disease and vitamin K deficiency. Vitamin K deficiency is partly corrected by vitamin K supplementation orally, and vitamin K administered IV additionally improves vitamin K status, as shown by further decrease of PIVKA-II and improved thrombin generation.
Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Hemorragia/tratamento farmacológico , Deficiência de Vitamina K/tratamento farmacológico , Vitamina K/administração & dosagem , Síndrome de Zellweger/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adolescente , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/epidemiologia , Criança , Feminino , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Países Baixos/epidemiologia , Projetos Piloto , Estudo de Prova de Conceito , Estudos Prospectivos , Precursores de Proteínas/sangue , Protrombina , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/diagnóstico , Deficiência de Vitamina K/epidemiologia , Adulto Jovem , Síndrome de Zellweger/sangue , Síndrome de Zellweger/diagnóstico , Síndrome de Zellweger/epidemiologiaRESUMO
Cardiovascular diseases are prevalent in patients with chronic obstructive pulmonary disease (COPD). Their coexistence implies that many COPD patients require anticoagulation therapy. Although more and more replaced by direct oral anticoagulants, vitamin K antagonists (VKAs) are still widely used. VKAs induce profound deficiency of vitamin K, a key activator in the coagulation pathway. It is recognized however that vitamin K is also an essential cofactor in the activation of other extrahepatic proteins, such as matrix Gla protein (MGP), a potent inhibitor of arterial calcification. No or insufficient MGP activation by the use of VKAs is associated with a rapid progression of vascular calcification, which may enhance the risk for overt cardiovascular disease. Vitamin K consumption, on the other hand, seems to have a protective effect on the mineralization of arteries. Furthermore, vascular calcification mutually relates to elastin degradation, which is accelerated in patients with COPD associating with impaired survival. In this commentary, we hypothesize that vitamin K is a critical determinant to the rate of elastin degradation. We speculate on the potential link between poor vitamin K status and crucial mechanisms of COPD pathogenesis and raise concerns about the use of VKAs in patients with this disease. Future intervention studies are needed to explore if vitamin K supplementation is able to reduce elastin degradation and vascular calcification in COPD patients.
Assuntos
Doenças Cardiovasculares/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Deficiência de Vitamina K/sangue , Vitamina K/sangue , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Suplementos Nutricionais , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Calcificação Vascular/sangue , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/epidemiologia , Vitamina K/administração & dosagem , Vitamina K/antagonistas & inibidores , Deficiência de Vitamina K/tratamento farmacológico , Deficiência de Vitamina K/epidemiologiaRESUMO
Subclinical vitamin K deficiency is prevalent among renal transplant recipients and is associated with an increased risk of cardiovascular disease. However, the association between vitamin K supplementation and improvement of arterial stiffness has not been explored in the renal transplant population. The KING trial (vitamin K2 In reNal Graft) is a single-arm study that evaluated the association between the change in vitamin K status and indices of arterial stiffness following 8 weeks of menaquinone-7 (vitamin K2) supplementation (360 µg once daily) among renal transplant recipients (n = 60). Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Subclinical vitamin K deficiency was defined as plasma concentration of dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.At baseline, 53.3% of the study subjects had subclinical vitamin K deficiency. Supplementation was associated with a 14.2% reduction in mean cfPWV at 8 weeks (cfPWV pre-vitamin K2 = 9.8 ± 2.2 m/s vs. cfPWV post-vitamin K2 = 8.4 ± 1.5 m/s; P < .001). Mean dp-ucMGP concentrations were also significantly reduced by 55.1% following menaquinone-7 supplementation with a reduction in the prevalence of subclinical deficiency by 40% (P = .001). When controlled for age, durations of hemodialysis and transplantation, and the change in 24-hour mean arterial pressure, the improvement in arterial stiffness was independently associated with the reduction in dp-ucMGP concentration (P = .014).Among renal transplant recipients with stable graft function, vitamin K2 supplementation was associated with improvement in subclinical vitamin K deficiency and arterial stiffness. (Clinicaltrials.gov: NCT02517580).
Assuntos
Falência Renal Crônica/terapia , Transplante de Rim , Rigidez Vascular/efeitos dos fármacos , Vitamina K 2/uso terapêutico , Deficiência de Vitamina K/tratamento farmacológico , Vitaminas/uso terapêutico , Adulto , Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/sangue , Suplementos Nutricionais , Proteínas da Matriz Extracelular/sangue , Feminino , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Estudos Prospectivos , Análise de Onda de Pulso , Diálise Renal , Resultado do Tratamento , Calcificação Vascular/sangue , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/epidemiologia , Vitamina K/sangue , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/epidemiologia , Proteína de Matriz GlaRESUMO
BACKGROUND: Vascular calcifications are highly prevalent in hemodialysis patients. Dephosphorylated-uncarboxylated MGP (dp-ucMGP) was found to increase in vitamin K-deficient patients and may be associated with vascular calcifications. Supplementation of hemodialysis patients with vitamin K2 (menaquinone-7) has been studied in Europe with a maximum 61% drop of dp-ucMGP levels. The aim of this study is to assess first the drop of dp-ucMGP in an Eastern Mediterranean cohort after vitamin K2 treatment and second the correlation between baseline dp-ucMGP and vascular calcification score. METHODS: This is a prospective, pre-post intervention clinical trial involving 50 hemodialysis patients who received daily 360 µg of menaquinone-7 for 4 weeks. At baseline they were assessed for plasma dp-ucMGP levels and vascular calcification scores (AC-24) as well as for other demographic, clinical and biological variables. Dp-ucMGP levels were measured a second time at 4 weeks. RESULTS: At baseline, dp-ucMGP levels were extremely elevated with a median of 3179.15 (1825.25; 4339.50) pM and correlated significantly with AC-24 (Spearman's rho = 0.43, P = 0.002). Using a bivariate regression analysis, the association between dp-ucMGP levels and AC-24 was most significant when comparing dp-ucMGP levels less than 1000 to those more than 1000 pM (P = 0.02). Dp-ucMGP levels higher than 5000 pM were significantly associated with females, patients with recent fracture and patients with lower serum albumin (respectively P = 0.02, 0.004 and 0.046). The average drop of dp-ucMGP at 4 weeks of treatment was found to be 86% with diabetics having the lowest drop rate (P = 0.01). CONCLUSION: Vitamin K deficiency, as assessed by high dp-ucMGP levels, is profound in hemodialysis patients from the Eastern Mediterranean region and it is significantly correlated with vascular calcifications. Daily 360 µg of menaquinone-7, given for 4 weeks, effectively reduces dp-ucMGP in this population. Future studies are needed to assess the changes in vascular calcifications in hemodialysis patients treated with vitamin K2 over a longer follow-up period. TRIAL REGISTRATION: The clinical trial was registered on clinicaltrials.gov (Identification number NCT02876354 , on August 11, 2016).
Assuntos
Proteínas de Ligação ao Cálcio/sangue , Proteínas da Matriz Extracelular/sangue , Diálise Renal/efeitos adversos , Vitamina K 2/uso terapêutico , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação/fisiologia , Estudos Prospectivos , Diálise Renal/tendências , Fatores de Risco , Resultado do Tratamento , Deficiência de Vitamina K/etiologia , Proteína de Matriz GlaRESUMO
Vitamin K is known for supporting the carboxylation of hepatic coagulation proteins. Levels of proteins induced by vitamin K absence for factor II (PIVKA-II) reflect hypocarboxylated prothrombin and can be used to detect subclinical vitamin K deficiency. The aim of this study was to determine the prevalence of perioperative subclinical vitamin K deficiency among neurosurgical patients using PIVKA-II and investigate the existence of any correlation to standard coagulation assays. Also, the antitumor effects of vitamin K were reviewed. Thirty-five patients undergoing brain tumor resection were included. Blood samples were drawn preoperatively, at the end of surgery and in the morning after surgery. In addition to PIVKA-II, factor II and the Owren and Quick prothrombin times were analyzed. Seventeen of 35 patients had elevated PIVKA-II levels before surgery, which continued to be above normal range postoperatively. Median PIVKA-II and Owren prothrombin time (PT-INR) were increased on the morning day 1 postoperatively compared to before surgery, whereas Quick end-stage prothrombin time (EPT) decreased and factor II was unaffected. Postoperative complications were connected to high PIVKA-II increases. Positive correlations between PIVKA-II and factor II and body mass index (BMI) were found. In conclusion, PIVKA-II was increased in many patients preoperatively and then increased by the morning following surgery. Standard coagulation assays were largely non-pathological. Correlations were demonstrated between PIVKA-II and factor II and BMI. The effect of perioperative treatment with different vitamin K supplements should be investigated in future studies, as well as clinical trials evaluating their antitumor effects.
Assuntos
Biomarcadores/sangue , Procedimentos Neurocirúrgicos , Precursores de Proteínas/sangue , Deficiência de Vitamina K/complicações , Idoso , Índice de Massa Corporal , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Protrombina , Deficiência de Vitamina K/sangueAssuntos
Suplementos Nutricionais , Insuficiência Renal Crônica/metabolismo , Deficiência de Vitamina K/metabolismo , Vitamina K/metabolismo , Humanos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/dietoterapia , Vitamina K/administração & dosagem , Vitamina K/sangue , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/dietoterapiaRESUMO
BACKGROUND & AIMS: Vitamin K acts as a coenzyme in the γ-carboxylation of vitamin K-dependent proteins, including coagulation factors, osteocalcin, matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6) protein. Osteocalcin is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification. GAS6 activity prevents the apoptosis of vascular smooth muscle cells. Few data on vitamin K intake in chronic kidney disease patients and no data in patients on a Mediterranean diet are available. In the present study, we evaluate the dietary intake of vitamin K1 in a cohort of patients undergoing haemodialysis. METHODS: In this multi-centre controlled observational study, data were collected from 91 patients aged >18 years on dialysis treatment for at least 12 months and from 85 age-matched control subjects with normal renal function. Participants completed a food journal of seven consecutive days for the estimation of dietary intakes of macro- and micro-nutrients (minerals and vitamins). RESULTS: Compared to controls, dialysis patients had a significant lower total energy intake, along with a lower dietary intake of proteins, fats, carbohydrates, fibres, and of all the examined minerals (Ca, P, Fe, Na, K, Zn, Cu, and Mg). With the exception of vitamin B12, vitamins intake followed a similar pattern, with a lower intake in vitamin A, B1, B2, C, D, E, folates, K1 and PP. These finding were confirmed also when normalized for total energy intake or for body weight. In respect to the adequate intakes recommended in the literature, the prevalence of a deficient vitamin K intake was very high (70-90%) and roughly double than in controls. Multivariate logistic model identified vitamin A and iron intake as predictors of vitamin K deficiency. CONCLUSIONS: Haemodialysis patients had a significantly low intake in vitamin K1, which could contribute to increase the risk of bone fractures and vascular calcifications. Since the deficiency of vitamin K intake seems to be remarkable, dietary counselling to HD patients should also address the adequacy of vitamin K dietary intake and bioavailability. Whether diets with higher amounts of vitamin K1 or vitamin K supplementation can improve clinical outcomes in dialysis patients remains to be demonstrated.
Assuntos
Dieta , Diálise Renal , Insuficiência Renal Crônica/sangue , Vitamina K 1/administração & dosagem , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Feminino , Humanos , Masculino , Micronutrientes/administração & dosagem , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Prevalência , Recomendações Nutricionais , Insuficiência Renal Crônica/tratamento farmacológico , Estudos Retrospectivos , Vitamina K 1/sangue , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/diagnóstico , Deficiência de Vitamina K/tratamento farmacológico , Circunferência da CinturaRESUMO
Vitamin K deficiency is associated with malnutrition in some complications, such as hyperemesis gravidarum, active gastrointestinal diseases, and psychological disorders. Maternal vitamin K deficiency can cause fetal bleeding, in particular, fetal intracranial hemorrhage. Although fetal hemorrhage is uncommon, severe damage to the fetus may be inevitable. We describe a pregnant woman with vitamin K deficiency possibly due to hyperemesis gravidarum. The patient was treated for the deficiency, and no fetal or neonatal hemorrhagic diseases were manifested.