Vitamin K intake and status are low in hemodialysis patients

Abstract

Vitamin K is essential for the activity of γ-carboxyglutamate (Gla)-proteins including matrix Gla28 protein and osteocalcin; an inhibitor of vascular calcification and a bone matrix protein, respectively. Insufficient vitamin K intake leads to the production of non-carboxylated, inactive proteins and this could contribute to the high risk of vascular calcification in hemodialysis patients. To help resolve this, we measured vitamin K(1) and K(2) intake (4-day food record), and the vitamin K status in 40 hemodialysis patients. The intake was low in these patients (median 140 μg/day), especially on days of dialysis and the weekend as compared to intakes reported in a reference population of healthy adults (mean K(1) and K(2) intake 200 μg/day and 31 μg/day, respectively). Non-carboxylated bone and coagulation proteins were found to be elevated in 33 hemodialysis patients, indicating subclinical hepatic vitamin K deficiency. Additionally, very high non-carboxylated matrix Gla28 protein levels, endemic to all patients, suggest vascular vitamin K deficiency. Thus, compared to healthy individuals, hemodialysis patients have a poor overall vitamin K status due to low intake. A randomized controlled trial is needed to test whether vitamin K supplementation reduces the risk of arterial calcification and mortality in hemodialysis patients.

Patients' Characteristics Affect the Survival Benefit of Warfarin Treatment for Hemodialysis Patients with Atrial Fibrillation. A Historical Cohort Study

“…Additionally, patients treated with VKA for prolonged time (greater than 1 year) have a higher risk of vascular calcifications [44,47] and increased arterial stiffness [48] , two major risk factors for cardiovascular mortality [49] , independent of other well-known risk factors including serum levels of bone markers. Such effects are similar to those observed in patients with vitamin K deficiency [50] and might be particularly strong in HD patients for whom the activity of Matrix γ-carboxyglutamate proteins, a group of vitamin K-dependent proteins inhibiting vascular mineral deposition, is severely hampered [29,47,48] . Our design cannot completely rule out the alternative hypothesis that residual bias by indication affected our risk estimates.…”

“…Among AF patients without ESRD, warfarin prevents mortality and strongly reduces the risk of stroke [40] . Due to platelet dysfunction, reduced dietary vitamin K intake, altered bioavailability, higher susceptibility to vascular calcifications, HD patients may have a less favorable riskbenefit profile compared to non-ESRD patients with AF [26][27][28][29] . Epidemiological studies seem to corroborate such hypothesis: a recent meta-analysis showed that VKA does not reduce the risk of stroke and increase the risk of bleeding among ESRD patients with AF [24] .…”

“…Concerns with the use of VKAs include initial overdosing due to vitamin K deficiency in ESRD, heparin use during dialysis, impaired platelet and coagulation function, and the possibility that warfarin may increase calcification formation in ESRD patients [25][26][27][28][29] .…”

New Perspectives for the Nutritional Value of Vitamin K in Human Health

“…Also, increased calcification of aortic valves was observed in patients receiving preoperative VKAs relative to non-treated patients [34,35]. Chronic kidney disease (CKD) patients, a population with a high prevalence of cardiovascular mortality and vascular calcifications, have been associated with subclinical vitamin K deficiency [35,36]. In a CKD rat model, warfarin treatments increased vascular calcification while high dietary vitamin K1 increased vitamin K tissue concentrations and attenuated vascular calcification [37].…”

Vitamin K and bone

“…The predominant dietary form of vitamin K in the USA, Europe, and most Western countries is phylloquinone, while the major form in Japan is menaquinones, especially menaquinone 7 (MK-7), which is a component of natto (3). Few data are available on vitamin K intake both in the general population and in chronic kidney disease patients (32). Recently, we evaluated the dietary intake of PK in a cohort of patients undergoing hemodialysis (33).…”