Patients with CKD are 10 - 30 times more likely to die from cardiovascular disease (CVD) compared to the general population and are also more likely to die from CVD than progress to end-stage kidney disease (ESKD). It is therefore imperative to find strategies to address CVD risk in earlier stages of CKD. Patients with early or moderate CKD develop vascular calcification and arterial stiffness, which increase the risk for subsequent CVD events and further declines in kidney function. Currently, there are no therapies known to reduce vascular calcification progression. One potential candidate is vitamin K because vitamin K and vitamin K-dependent proteins are present in vascular tissue. For example, matrix gla protein (MGP) is a calcification inhibitor in vascular tissue that requires vitamin K to function. In rats with CKD, a high vitamin K diet increased functional MGP and reduced vascular calcification and arterial stiffness. Consistent with this, early evidence from human studies generally supports a role for vitamin K in protecting against vascular calcification progression. Before this finding is extrapolated to CKD patients, who are more likely to have both vascular calcification and vitamin K insufficiency, it is imperative to determine if vitamin K status is similarly associated with these cardiovascular outcomes in CKD, as this relationship may be affected by other pathologies common in CKD. To fill this research gap we propose to measure plasma phylloquinone (vitamin K1) and uncarboxylated MGP (ucMGP), a global and functional circulating biomarker of vitamin K status respectively, in the Chronic Renal Insufficiency Cohort (CRIC), a cohort of nearly 4000 patients with early or moderate CKD, and determine the association with clinical atherosclerotic CVD, arterial calcification and stiffness, and kidney function decline. Our findings will help clarify the importance of vitamin K in CKD. Identifying strategies to reduce CVD and CKD progression in CKD is important because intervening at this stage would prolong the time to ESKD and time to dialysis ? which holds substantial clinical and public health benefits.
The proposed research is relevant to public health and NIDDKs mission to conduct research in kidney disease to improve people?s quality of life. A better understanding vitamin K?s role in cardiovascular disease and chronic kidney disease (CKD) progression in patients with CKD offers a potentially important, novel, and low- cost intervention for a high-risk patient population and may eventually lead to new treatment strategies.