RESUMO
PURPOSE: To investigate whether patients with severe motor and intellectual disability (SMID) have nutritional vitamin D and K insufficiencies and clarify the required vitamin supplementation. METHODS: This prospective observational study enrolled Japanese adults with SMID receiving institutionalized care who underwent blood sampling between February 2020 and February 2022 during annual medical checkups. Serum vitamin K1 and 25-hydroxy vitamin D (25(OH)D) levels were measured to determine their relationship with serum uncarboxylated osteocalcin (ucOC) levels. Vitamin D and K intake was compared among tube-fed and oral-intake patients with SMID and control participants using corresponding serum levels. RESULTS: The study included 124 patients with SMID (56 men and 68 women; mean age: 53.0 years) and 20 control participants. Serum 25(OH)D levels were significantly higher in the SMID group than in the control group and the oral intake SMID group than in the tube-fed SMID group. In the tube-fed SMID group, vitamin D intake was lower than the daily recommended intake and correlated with serum 25(OH)D levels. Daily vitamin K intake in the tube-fed group was lower than recommended but not correlated with serum vitamin K levels. Serum ucOC levels were significantly higher in the SMID group than in the control group. Tube feeding was significantly and positively correlated with serum 25(OH)D levels. Serum 25(OH)D levels were not correlated with serum vitamin K1 levels. CONCLUSIONS: The SMID group had higher ucOC levels than the control group, possibly owing to daily vitamin K and D deficiencies. Vitamin D supplementation is recommended to decrease ucOC levels.
Assuntos
Deficiência Intelectual , Vitamina D , Vitamina K 1 , Humanos , Feminino , Masculino , Vitamina K 1/sangue , Deficiência Intelectual/sangue , Pessoa de Meia-Idade , Vitamina D/sangue , Vitamina D/análogos & derivados , Japão , Adulto , Estudos Prospectivos , Idoso , Deficiência de Vitamina K/sangue , Deficiência de Vitamina D/sangue , Osteocalcina/sangue , População do Leste AsiáticoRESUMO
The available evidence on vitamin K status in cystic fibrosis (CF) is scarce, lacking data on vitamin K2 (menaquinones-MK). Therefore, we assessed vitamin K1, MK-4 and MK-7 concentrations (LC-MS/MS) in 63 pancreatic insufficient and modulator naïve CF patients, and compared to 61 healthy subjects (HS). Vitamin K1 levels did not differ between studied groups. MK-4 concentrations were higher (median <1st-3rd quartile>: 0.778 <0.589-1.086> vs. 0.349 <0.256-0.469>, p < 0.0001) and MK-7 levels lower (0.150 <0.094-0.259> vs. 0.231 <0.191-0.315>, p = 0.0007) in CF patients than in HS. MK-7 concentrations were higher in CF patients receiving K1 and MK-7 supplementation than in those receiving vitamin K1 alone or no supplementation. Moreover, vitamin K1 concentrations depended on the supplementation regime. Based on multivariate logistic regression analysis, we have found that MK-7 supplementation dose has been the only predictive factor for MK-7 levels. In conclusion, vitamin K1 levels in CF are low if not currently supplemented. MK-4 concentrations in CF patients supplemented with large doses of vitamin K1 are higher than in HS. MK-7 levels in CF subjects not receiving MK-7 supplementation, with no regard to vitamin K1 supplementation, are low. There do not seem to be any good clinical predictive factors for vitamin K status.
Assuntos
Fibrose Cística , Protrombina , Vitamina K 1 , Vitamina K 2 , Humanos , Fibrose Cística/sangue , Feminino , Masculino , Vitamina K 2/sangue , Vitamina K 2/análogos & derivados , Estudos Transversais , Protrombina/análise , Adolescente , Adulto , Vitamina K 1/administração & dosagem , Vitamina K 1/sangue , Adulto Jovem , Estado Nutricional , Suplementos Nutricionais , Deficiência de Vitamina K/sangue , Vitamina K/sangueRESUMO
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
High circulating dephosphorylated (dp) uncarboxylated (uc) matrix Gla protein (MGP) and uc osteocalcin (OC) concentrations are regarded as markers of vitamin K-deficiency. However, because MGP and OC are small molecules, they may potentially pass the glomerulus, and their blood concentrations may strongly depend on kidney function. However, many studies with vitamin K-status parameters do not structurally adjust for baseline kidney function, and detailed studies on kidney function-dependence of vitamin K-status markers are lacking. We therefore measured plasma dp-ucMGP using a chemiluminescent assay in 578 kidney transplant recipients (41% females, age 56 ± 13y, 7.5 (3.2 to 13.7)y after transplantation, eGFR 49 ± 17 mL/min/1.73 m2) participating in the prospective TransplantLines Cohort Studies. Additionally, dp-carboxylated MGP, ucOC and carboxylated OC were measured using ELISA in plasma of a subgroup of 60 participants. Finally, dp-ucMGP was measured in a separate cohort of 124 kidney transplant recipients before and three months after kidney transplantation. Dp-ucMGP positively correlated with creatinine, cystatin C, and negatively with eGFR (Spearman's ρ 0.54, 0.60, and -0.54, respectively, p < 0.001 for all), and each 10 mL/min/1.73 m2 increase in eGFR was associated with a 14.0% lower dp-ucMGP. Additionally, dp-ucMGP strongly declined after kidney transplantation (pretransplantation: 1252 (868 to 1744) pmol/L to posttransplantation: 609 (451 to 914) pmol/L, p < 0.001). Proportions of dp-ucMGP over total MGP and ucOC over total OC were not associated with eGFR. This study highlights that dp-ucMGP is strongly associated with kidney function, and that levels strongly decrease after kidney transplantation. We therefore propose adequate adjustment for kidney function, or the use of kidney function-independent parameters such as proportion of uncarboxylated MGP or OC in the assessment of vitamin K-status in clinical practice and research.
Assuntos
Transplante de Rim , Rim/fisiopatologia , Complicações Pós-Operatórias/sangue , Deficiência de Vitamina K/sangue , Vitamina K/sangue , Bancos de Espécimes Biológicos , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Países Baixos , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Deficiência de Vitamina K/fisiopatologiaRESUMO
It has recently been hypothesized that vitamin K could play a role in COVID-19. We aimed to test the hypotheses that low vitamin K status is a common characteristic of patients hospitalized with COVID-19 compared to population controls and that low vitamin K status predicts mortality in COVID-19 patients. In a cohort of 138 COVID-19 patients and 138 population controls, we measured plasma dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), which reflects the functional vitamin K status in peripheral tissue. Forty-three patients died within 90 days from admission. In patients, levels of dp-ucMGP differed significantly between survivors (mean 877; 95% CI: 778; 995) and non-survivors (mean 1445; 95% CI: 1148; 1820). Furthermore, levels of dp-ucMGP (pmol/L) were considerably higher in patients (mean 1022; 95% CI: 912; 1151) compared to controls (mean 509; 95% CI: 485; 540). Cox regression survival analysis showed that increasing levels of dp-ucMGP (reflecting low vitamin K status) were associated with higher mortality risk (sex- and age-adjusted hazard ratio per doubling of dp-ucMGP was 1.49, 95% CI: 1.03; 2.24). The association attenuated and became statistically insignificant after adjustment for co-morbidities (sex, age, CVD, diabetes, BMI, and eGFR adjusted hazard ratio per doubling of dp-ucMGP was 1.22, 95% CI: 0.82; 1.80). In conclusion, we found that low vitamin K status was associated with mortality in patients with COVID-19 in sex- and age-adjusted analyses, but not in analyses additionally adjusted for co-morbidities. Randomized clinical trials would be needed to clarify a potential role, if any, of vitamin K in the course of COVID-19.
Assuntos
COVID-19/mortalidade , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Hospitalização , Deficiência de Vitamina K/mortalidade , Vitamina K/sangue , Adulto , Idoso , Biomarcadores/sangue , Coagulação Sanguínea , COVID-19/complicações , COVID-19/metabolismo , Proteínas de Ligação ao Cálcio/sangue , Estudos de Coortes , Proteínas da Matriz Extracelular/sangue , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Regressão , SARS-CoV-2 , Trombose/metabolismo , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/complicações , Adulto Jovem , 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
Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01-1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01-1.48 and 1.27, 1.01-1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.
Assuntos
Insuficiência Renal Crônica/complicações , Calcificação Vascular/complicações , Deficiência de Vitamina K/complicações , Vitamina K/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/sangue , Estudos de Coortes , Proteínas da Matriz Extracelular/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/patologia , Taxa de Sobrevida , Calcificação Vascular/sangue , Calcificação Vascular/mortalidade , Calcificação Vascular/patologia , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/mortalidade , Deficiência de Vitamina K/patologia , Proteína de Matriz GlaRESUMO
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
We present a family who suffered recurrent sibling losses due to vitamin K deficiency bleed. The index child was asymptomatic at presentation, had normal clinical examination, and was investigated for coagulation disorders in view of previous 3 sibling losses as a result of intracranial hemorrhage. His investigations showed deranged coagulogram and clotting factors' assay. The baby was given vitamin K1 1 mg intramuscularly following which his coagulogram and clotting factors' assay returned to normal. The genetic analysis did not identify any inherited cause of bleeding tendency. The significant family history, exclusive breastfeeding, no diarrhea, failure to thrive or drug use, no prophylaxis with vitamin K at birth, recovery of clotting factors on vitamin K administration, and a corroborative molecular analysis confirmed diagnosis of vitamin K deficiency in the index child. This case gives a strong reminder not to miss birth dose of vitamin K in any neonate.
Assuntos
Antifibrinolíticos/uso terapêutico , Hemorragias Intracranianas/tratamento farmacológico , Deficiência de Vitamina K/tratamento farmacológico , Vitamina K/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/etiologia , Masculino , Irmãos , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/complicaçõesRESUMO
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
This is the first study to evaluate vitamin K status in relation to dietary intake and phenylalanine dietary compliance in patients with phenylketonuria (PKU). The dietary and PKU formula intake of vitamin K was calculated in 34 PKU patients, with vitamin K status determined by the measurement of prothrombin induced by vitamin K absence (PIVKA-II). Blood phenylalanine concentrations in the preceding 12 months were considered. There were significantly more phenylalanine results exceeding 6 mg/dL in patients with normal PIVKA-II concentrations than in those with abnormal PIVKA-II levels (p = 0.035). Similarly, a higher total intake of vitamin K and dietary vitamin intake expressed as µg/day (p = 0.033 for both) and %RDA (p = 0.0002 and p = 0.003, respectively) was observed in patients with normal PIVKA-II levels. Abnormal PIVKA-II concentrations were associated with a lower OR (0.1607; 95%CI: 0.0273-0.9445, p = 0.043) of having a median phenylalanine concentration higher than 6 mg/dL. In conclusion, vitamin K deficiency is not uncommon in phenylketonuria and may also occur in patients with adequate vitamin K intake. PKU patients with better dietary compliance have a higher risk of vitamin K deficiency. The present findings highlight the need for further studies to re-evaluate dietary recommendations regarding vitamin K intake, both concerning formula-based and dietary consumption of natural products.
Assuntos
Estado Nutricional , Cooperação do Paciente , Fenilalanina/sangue , Fenilcetonúrias/dietoterapia , Deficiência de Vitamina K/sangue , Vitamina K/administração & dosagem , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Necessidades Nutricionais , Fenilalanina/administração & dosagem , Protrombina/metabolismo , Adulto JovemAssuntos
Transfusão de Eritrócitos , Trombose Intracraniana , Imageamento por Ressonância Magnética , Plasma , Trombose Venosa , Deficiência de Vitamina K , Vitamina K/administração & dosagem , Humanos , Lactente , Trombose Intracraniana/sangue , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/terapia , Masculino , Trombose Venosa/sangue , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/diagnóstico por imagem , Deficiência de Vitamina K/terapiaRESUMO
BACKGROUND: Dephosphorylated uncarboxylated matrix Gla-protein (dp-ucMGP) is a biomarker of functional vitamin K status. High plasma dp-ucMGP concentrations reflect a low vitamin K status and have been related to vascular calcification. Our aims were to assess plasma levels of dp-ucMGP and their association with cardiovascular risk in a general population. METHODS: Plasma dp-ucMGP measurements were performed using the IDS-iSYS InaKtif MGP assay in 491 consecutive participants in a Danish general population study (229 males and 262 females, aged 19-71 years). Multivariable linear and logistic regressions were used to assess the association between dp-ucMGP levels and cardiovascular risk factors. RESULTS: Mean ± standard deviation (SD) for dp-ucMGP was 465 ± 181 pmol/L, and upper 95th percentile was 690 pmol/L. In logistic regression analyses, an increase in dp-ucMGP category (<300, 300-399, 400-499, ≥500 pmol/L) was positively associated with obesity, odds ratio (OR) 2.27 (95% confidence interval (CI) 1.54-3.33), history of cardiovascular disease, OR 1.77 (CI 1.02-3.05), and above-median estimated pulse wave velocity (ePWV), OR 1.54 (CI 1.21-1.96), when adjusted for age, sex, and lifestyle factors. 1 SD increase in diastolic and systolic blood pressure (BP) corresponded to a 5.5% (CI 2.9-8.0%) and 4.7% (CI 2.1-7.4%) increase in dp-ucMGP, respectively, when adjusted for age and sex. CONCLUSION: Plasma dp-ucMGP levels were positively associated with obesity, BP, ePWV, and history of cardiovascular disease. These findings support that dp-ucMGP is a biomarker of cardiovascular risk, and that vitamin K status could play a role in vascular calcification. The strong association with obesity deserves further attention.
Assuntos
Proteínas de Ligação ao Cálcio/sangue , Doenças Cardiovasculares/sangue , Proteínas da Matriz Extracelular/sangue , Deficiência de Vitamina K/sangue , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Dinamarca/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade , Razão de Chances , Calcificação Vascular/sangue , Deficiência de Vitamina K/complicações , Adulto Jovem , Proteína de Matriz GlaRESUMO
Gut microbial metabolism is not only an important source of uremic toxins but may also help to maintain the vitamin K stores of the host. We hypothesized that sevelamer therapy, a commonly used phosphate binder in patients with end-stage kidney disease (ESKD), associates with a disturbed gut microbial metabolism. Important representatives of gut-derived uremic toxins, including indoxyl sulfate (IndS), p-Cresyl sulfate (pCS), trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAG) and non-phosphorylated, uncarboxylated matrix-Gla protein (dp-ucMGP; a marker of vitamin K status), were analyzed in blood samples from 423 patients (65% males, median age 54 years) with ESKD. Demographics and laboratory data were extracted from electronic files. Sevelamer users (n = 172, 41%) were characterized by higher phosphate, IndS, TMAO, PAG and dp-ucMGP levels compared to non-users. Sevelamer was significantly associated with increased IndS, PAG and dp-ucMGP levels, independent of age, sex, calcium-containing phosphate binder, cohort, phosphate, creatinine and dialysis vintage. High dp-ucMGP levels, reflecting vitamin K deficiency, were independently and positively associated with PAG and TMAO levels. Sevelamer therapy associates with an unfavorable gut microbial metabolism pattern. Although the observational design precludes causal inference, present findings implicate a disturbed microbial metabolism and vitamin K deficiency as potential trade-offs of sevelamer therapy.
Assuntos
Bactérias/efeitos dos fármacos , Toxinas Bacterianas/sangue , Quelantes/efeitos adversos , Colo/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Falência Renal Crônica/tratamento farmacológico , Sevelamer/efeitos adversos , Uremia/tratamento farmacológico , Deficiência de Vitamina K/induzido quimicamente , Adulto , Idoso , Bactérias/metabolismo , Biomarcadores/sangue , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/microbiologia , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Fatores de Risco , Resultado do Tratamento , Uremia/sangue , Uremia/microbiologia , Deficiência de Vitamina K/sangueRESUMO
Vitamin K is required for the É£-carboxylation of specific glutamic acid residues within the Gla domain of the 17 vitamin K-dependent proteins (VKDPs). The timely detection and correction of vitamin K deficiency can protect against bleeding. Vitamin K also plays a role in bone metabolism and vascular calcification. Patients at increased risk of vitamin K deficiency include those with a restricted diet or malnutrition, lipid malabsorption, cancer, renal disease, neonates and the elderly. Coagulation assays such as the prothrombin time have been used erroneously as indicators of vitamin K status, lacking sufficient sensitivity and specificity for this application. The measurement of phylloquinone (K1) in serum is the most commonly used marker of vitamin K status and reflects abundance of the vitamin. Concentrations <0.15 µg/L are indicative of deficiency. Disadvantages of this approach include exclusion of the other vitamin K homologues and interference from recent dietary intake. The cellular utilisation of vitamin K is determined through measurement of the prevalence of undercarboxylated VKDPs. Most commonly, undercarboxylated prothrombin (Protein Induced by Vitamin K Absence/antagonism, PIVKA-II) is used (reference range 17.4-50.9 mAU/mL (Abbott Architect), providing a retrospective indicator of hepatic vitamin K status. Current clinical applications of PIVKA-II include supporting the diagnosis of vitamin K deficiency bleeding of the newborn, monitoring exposure to vitamin K antagonists, and when used in combination with α-fetoprotein, as a diagnostic marker of hepatocellular carcinoma. Using K1 and PIVKA-II in tandem is an approach that can be used successfully for many patient cohorts, providing insight into both abundance and utilisation of the vitamin.
Assuntos
Análise Química do Sangue , Deficiência de Vitamina K/diagnóstico , Vitamina K/sangue , Biomarcadores/sangue , Análise Química do Sangue/normas , Testes de Coagulação Sanguínea , Humanos , Valor Preditivo dos Testes , Precursores de Proteínas/sangue , Protrombina , Reprodutibilidade dos Testes , Vitamina K 1/sangue , Deficiência de Vitamina K/sangue , Sangramento por Deficiência de Vitamina K/sangue , Sangramento por Deficiência de Vitamina K/diagnósticoRESUMO
BACKGROUND: Alpha-fetoprotein (AFP) has received extensive attention in the differential diagnosis of hepatocellular carcinoma (HCC), especially for AFP-negative HCC (AFP-NHCC). The current study aimed to explore the value of targeted regulation of LHPP expression-related microRNAs (miRs) and protein induced by vitamin K deficiency or antagonist-II (PIVKA-II) in the differential diagnosis of AFP-NHCC. METHODS: A retrospective study was conducted on a testing set-including 214 AFP-NHCC patients, 200 cirrhosis, and 210 controls, and a validation set-including 140 AFP-NHCC patients, 134 cirrhosis, and 128 controls recruited from The First Affiliated Hospital of Hunan Normal University. Serum miRs were examined using quantitative real-time PCR method. Serum PIVKA-II was measured by enzyme-linked immunosorbent assay. RESULTS: Compared with adjacent tissues, LHPP protein levels in cancer tissues were significantly decreased (P < .05). Predictive software and dual-luciferase reporter assays showed that miR-363-5p and miR-765 can target LHPP expression. Serum miR-363-5p, miR-765, and PIVKA-II levels were significantly higher in AFP-HCC patients than in cirrhosis and controls. A logistic regression model combining miR-363-5p, miR-765, and PIVKA-II was performed. This model presented a high discriminating value (AUC: 0.930, sensitivity/specificity: 79.4%/95.4%) than any single indicator. In the validation set, this model still showed a high discriminating value (AUC: 0.936, sensitivity/specificity: 83.6%/94.7%). CONCLUSION: Current model combining serum miR-363-5p, miR-765, and PIVKA-II has potential significance for diagnosis of AFP-NHCC.