Low vitamin K1 intake in haemodialysis patients.

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.

Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins.

Matrix Gla protein (MGP) and bone Gla protein (BGP) are two vitamin K-dependent proteins (VKDPs) involved in the regulation of vascular calcification (VC). We carried out a secondary analysis of the VIKI study to evaluate associations between drug consumption and VKDP levels in 387 hemodialyzed patients. The VIKI study assessed the prevalence of vitamin K deficiency in hemodialysis patients. We evaluated drug consumption, determined BGP and MGP levels, and verified the presence of any vertebral fractures (VF) and VC by spine radiographs. Total BGP levels were twice as high with calcimimetics versus no calcimimetics (290 vs. 158.5 mcg/L, p < 0.0001) and 69 % higher with vitamin D analogs (268 vs. 159 mcg/L, p < 0.0001). Total MGP was 19 % higher with calcimimetics (21.5 vs. 18.1 mcg/L, p = 0.04) and 54 % higher with calcium acetate (27.9 vs. 18.1 mcg/L, p = 0.003); no difference was found with vitamin D analogs (21.1 vs. 18.3 mcg/L, p = 0.43). Median Total BGP level was 29 % lower in patients with ≥1 VF (151 vs. 213 mcg/L, p = 0.0091) and 36 % lower in patients with VC (164 vs. 262.1 mcg/L, p = 0.0003). In non-survivors, median BGP and MGP were lower, but only for MGP this difference reached the statistical significance (152 vs. 191 mcg/L, p = 0.20 and 15.0 vs. 19.7 mcg/L, p = 0.02, respectively). Pending studies on vitamin K supplementation, calcimimetics, and vitamin D analogs may play a role in preserving vitamin K-dependent protein activity, thus contributing to bone and vascular health in CKD patients.

Fetal ductal constriction caused by maternal ingestion of green tea in late pregnancy: an experimental study.

OBJECTIVES: The aim of this study was to test the hypothesis that experimental maternal intake of green tea in late pregnancy causes fetal ductus arteriosus constriction, probably because of prostaglandin inhibition. METHODS AND RESULTS: Twelve fetal lambs (pregnancy > 120 days) were assessed before and after maternal administration of green tea (n = 8) or water (n = 4; controls) as the only source of liquid. After 1 week, echocardiography showed signs of constriction of the ductus arteriosus in all fetuses from mothers ingesting green tea, with increase in mean systolic velocity(from 0.70 ± 0.19 m/s to 0.92 ± 0.15 m/s, 31.4%, p = 0.001) and mean diastolic velocity (0.19 ± 0.05 m/s to 0.31 ± 0.01 m/s, 63.1%, p < 0.001), decrease of pulsatility index (2.2 ± 0.4 to 1.8 ± 0.3, 22.2%, p = 0.003) and increase of mean right ventricular/left ventricular diameter ratio (0.89 ± 0.14 to 1.43 ± 0.23, 60.6%, p < 0.001). In the four control fetuses, there were no significant changes. All lambs exposed to green tea also showed at autopsy dilated and hypertrophic right ventricles, which was not present in control fetuses. Histological analysis showed a significantly larger mean thickness of the medial avascular zone of the ductus arteriosus in fetuses exposed to green tea than in controls (747.6 ± 214.6 µm vs 255.3 ± 97.9 µm, p < 0.001). CONCLUSIONS: This study in fetal lambs shows a cause and effect relationship between experimental maternal exposure of green tea and fetal ductus arteriosus constriction in late pregnancy.