Vitamin K for the Treatment of Cardiovascular Disease in End-Stage Renal Disease Patients: Is there Hope?

In Chronic Kidney Disease, vascular calcification (VC) is highly prevalent even at early stages and is gradually enhanced, along with disease progression to End-Stage Renal Disease (ESRD). The calcification pattern in uremia includes all types of mineralization and contributes to the heavy cardiovascular (CV) burden that is common in these patients. Ectopic mineralization is the result of the imbalance between inhibitors and promoters of vascular calcification, with the latter overwhelming the former. The most powerful, natural inhibitor of calcification is Matrix Gla Protein (MGP), a small vitamin K dependent protein, secreted by chondrocytes and vascular smooth muscle cells. In uremia, MGP was reported as the only molecule able to reverse VC by "sweeping" calcium and hydroxyapatite crystals away from the arterial wall. To become biologically active, this protein needs to undergo carboxylation and phosphorylation, reactions highly dependent on vitamin K status. The inactive form of MGP reflects the deficiency of vitamin K and has been associated with CV events and mortality in ESRD patients. During the past decade, vitamin K status has emerged as a novel risk factor for vascular calcification and CV disease in various populations, including dialysis patients. This review presents evidence regarding the association between vitamin K and CV disease in ESRD patients, which are prone to atherosclerosis and atheromatosis.

Cervical spine stenosis and possible vitamin K deficiency embryopathy in an unusual case of chondrodysplasia punctata and an updated classification system.

We describe in this paper a patient with brachytelephalangic chondrodysplasia punctata (BCDP) who has multiple serious medical problems and striking physical abnormalities. These include cervical spine stenosis with resultant quadriplegia, severe nasal hypoplasia, and brachytelephalangy. Radiographs taken shortly after birth demonstrated extensive epiphyseal and vertebral stippling, and distal phalangeal hypoplasia. The pregnancy was complicated by maternal intestinal obstruction due to a small bowel carcinoma and probable malabsorption. The severity of the phenotype in this case may have been influenced by these maternal factors particularly vitamin K deficiency.

Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?

BACKGROUND: A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency. AIMS: To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density. METHODS: Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population. RESULTS: Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=-0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=-0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not. CONCLUSIONS: The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn's disease may have implications for the prevention and treatment of osteoporosis in this disorder.