Role of Vitamin K in Chronic Kidney Disease: A Focus on Bone and Cardiovascular Health

Abstract

Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic disturbances, bone tissue and metabolism alterations, and vascular calcification (VC) exists and has been defined as chronic kidney disease–mineral and bone disorder (CKD-MBD). Poor vitamin K status seems to have a key role in the progression of CKD, but also in the onset and advance of both bone and cardiovascular complications. Three forms of vitamin K are currently known: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC. This review focuses on the biochemical and functional characteristics of vitamin K vitamers, suggesting this nutrient as a possible marker of kidney, CV, and bone damage in the CKD population and exploring its potential use for promoting health in this clinical setting. Treatment strategies for CKD-associated osteoporosis and CV disease should include vitamin K supplementation. However, further randomized clinical studies are needed to assess the safety and the adequate dosage to prevent these CKD complications.

Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease?

“…VK1 deficiency has been observed in CKD patients and animals with experimental CKD [ 24 , 48 , 55 ], and in this respect our results are in line with these earlier observations. However, the ratios of MK7/VK1 and MK4/VK1, which provide an index of the efficiency of conversion of VK1 to vitamins K2 [ 56 ], were increased in uremic animals compared to controls.…”

“…The measurement of serum levels of VKDPs, like total osteocalcin and its undercarboxylated form, Glu-OC, are sensitive indirect tests in detecting subclinical VK deficiency [ 16 ]. Both total osteocalcin and Glu-OC were markedly increased in the serum of CKD rats in this experiment, and similar findings have been consistently observed by others in human and experimental CKD [ 19 , 24 , 48 ]. It is generally believed that the high percentage of Glu-OC reflects insufficient VK intake, low VK status, and impaired bone mineralization [ 28 , 29 , 30 ].…”

“…Although a high prevalence of subclinical vitamin K (VK) deficiency has been described in patients with CKD [ 18 , 19 , 20 , 21 , 22 ] and there are suggestions that this condition can impact bone quality [ 47 , 48 ], there are a lack of experimental data on this issue. To the best of our knowledge, this is the first comprehensive study in which we determined the endogenous VK metabolism, the bone levels of VK-dependent proteins (VKDPs), and the expression of VK cycle enzymes in femoral bone of rats with 5/6 nephrectomy.…”

Improving nutrition through biofortification–A systematic review

“…Vitamin K promotes coagulation and prevents excessive bleeding in children (38,39). Additionally, it aids in bone and muscle metabolism in adults (40,41). The recommended intake of Vitamin K for children and adults are 12 and 120 µg/day, respectively (24,26).…”

Improving Nutrition through Biofortification - A Systematic Review

“…Vitamin K (VitK) promotes coagulation and prevents excessive bleeding in children (Savarino et al, 2021). Additionally, it aids in bone and muscle metabolism in adults (Bellone et al, 2022;Cozzolino et al, 2019). The recommended intake of VitK for children and adults are 12 µg/day and 120 µg/day, respectively (Godswill et al, 2020;Savarino et al, 2021).…”