#5745 CORRELATION BETWEEN MATRIX GLA PROTEIN LEVEL AND EFFECT OF VITAMIN K2 THERAPY ON VASCULAR CALCIFICATION IN HEMODIALYSIS PATIENTS

Abstract

Abstract Background and Aims In hemodialysis patients, vascular calcifications are precocious, frequent, and excessive. The association between the level of vascular calcifications and mortality has been described in dialysis patients. The dephosphorylated and uncarboxylated matrix Gla protein (dp-ucMGP) is an indicator of vitamin K2 status and correlates with markers of vascular calcification. It is activated by γ glutamyl carboxylase that converts inactive matrix Gla protein into an active form, and vitamin K2 is a cofactor of this reaction. The active form of matrix Gla protein is a known inhibitor of arterial wall calcification and plays an essential role in bone turnover. The biological activity of the calcification-inhibitory matrix Gla protein can be achieved by simple administration of oral vitamin K2. Aim To assess the effect of vitamin k2 supplementation on vascular calcification and matrix Gla protein in hemodialysis patients. In addition, we wanted to clarify the role of vitamin k2 as prophylaxis against vascular calcification in hemodialysis patients not suffering from vascular calcifications. Method The study included 112 hemodialysis adult patients not receiving vitamin k antagonists. The study was conducted at the Urology and Nephrology Center, Mansoura University. Patients who suffered from vascular calcification (68 patients) received oral 180 μgr of vitamin K2 every day for one year. Uncarboxylated matrix Gla protein concentrations were quantified using ELISA before administering vitamin k2 and after 12 months of treatment. In addition, we used an abdominal CT scan to assess aortic calcification with Agatston score. The scan was performed at the beginning of the study and after 12 months of follow-up. Patients who did not suffer from vascular calcification (44 patients) were randomly assigned to either receive oral vitamin K2 or no treatment. Uncarboxylated matrix Gla protein concentrations were quantified using ELISA at randomization and 12 months. Aortic calcification was evaluated using Agatston score after an abdominal CT scan that was performed at the beginning and at 12 months of follow-up. Results There was a positive and statistically significant correlation between un-carboxylated matrix Gla protein level and vascular calcification (rs = 0.64, P-value < 0.001). Among patients with vascular calcification, the baseline plasma (dp-ucMGP) significantly decreased by 21.3% after treatment of vitamin k2 for one year. Besides, the median baseline calcium score significantly decreased by 15.1% after 1year of vitamin k2 treatment. On the other hand, patients without vascular calcification had their 1-year matrix GLA protein comparable between the two groups. Despite the reduction of matrix GLA protein in the vitamin k2 naïve group, there was no statistically significant difference. In addition, the calcium score after one year was comparable between both groups. Conclusion Hemodialysis patients are at risk of vascular calcification. There is a positive correlation between (dp-ucMGP) protein and vascular calcification. Supplementation of vitamin K2 is safe and improves the serum markers of its deficiency. Also, vitamin K2 supplementation slows the progression of calcification. On the other hand, there is a lack of strong evidence that vitamin K2 supplementation slows down the calcification progression in dialysis patients. Therefore, we recommend further studies to delineate the efficacy and cost-effectiveness of the drug.