Vitamin K and Kidney Transplantation

Abstract

The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches.

Vitamin K in CKD Bone Disorders

“…These reactions do not proceed in parallel, and, according to the level of carboxylation and/or phosphorylation, at least four different molecules can be found in circulation: (i) dephosphorylated-carboxylated MGP (dp-cMGP); (ii) dephosphorylated undercarboxylated MGP ( dp-ucMGP: vitamin k deficiency is characterized by dp-ucMGP levels higher 500 pmol/L) [29]; (iii) phosphorylated uncarboxylated MGP (p-ucMGP); (iv) phosphorylated carboxylated MGP (p-cMGP). The active form is both phosphorylated and carboxylated (p-cMGP) and its synthesis is stimulated by vitamin D [30].…”

“…Functional tests can be performed to estimate vitamin K blood levels indirectly; in particular, the measurement of undercarboxylated proteins, OC and MGP, has proved to be more sensitive than prothrombin time in detecting subclinical vitamin K deficiency [29]. In CKD patients, several studies assessed a poor vitamin K status either directly by means of low levels of serum phylloquinone or indirectly by high levels of ucOC, ucMGP and dp-ucMGP [29]. The poor Vitamin K status worsens parallel to the CKD progression jointly to the overall poor nutrients intake.…”

“…These findings could follow the maintenance of their dietary habits before transplantation, therefore contributing to the previous state of vitamin K insufficiency. Furthermore, body mass index, triglyceride level, mycophenolate mofetil use, and smoking have been identified as independent determinants of circulating dp-ucMGP levels in [29].…”

New aspects of microbial vitamin K2 production by expanding the product spectrum

“…Vitamin K serves as a cofactor for γ-glutamyl carboxylase (GGCX), which converts glutamic acid residues of vitamin K-dependent proteins (VKDPs) into γ-carboxyglutamic acid (Gla). There are more than 15 types of VKDPs, including coagulation factors II (prothrombin), VII, IX, and X, as well as the anti-coagulation factors C, protein S, and osteocalcin [ 4 – 7 ]. Additionally, optimal vitamin K status is strongly associated with various health benefits, such as preventing or alleviating cardiovascular disease, osteoporosis, osteoarthritis, cancer, inflammatory diseases, diabetes, chronic kidney disease, immune disorders, and Alzheimer’s disease [ 4 , 7 – 10 ].…”

“…There are more than 15 types of VKDPs, including coagulation factors II (prothrombin), VII, IX, and X, as well as the anti-coagulation factors C, protein S, and osteocalcin [ 4 – 7 ]. Additionally, optimal vitamin K status is strongly associated with various health benefits, such as preventing or alleviating cardiovascular disease, osteoporosis, osteoarthritis, cancer, inflammatory diseases, diabetes, chronic kidney disease, immune disorders, and Alzheimer’s disease [ 4 , 7 – 10 ]. Perhaps unsurprisingly, vitamin K deficiency may also influence the mortality and morbidity of COVID-19 patients [ 11 ].…”