CKD PATHOPHYSIOLOGY AND CLINICAL STUDIES

Introduction and Aims: Patients with chronic kidney disaeses (CKD) suffer from accelered vascular calcification (VC) and vitamin K defficiency.The vitamin K-dependent matrix Gla protein (MGP) is one of the most powerful inhibitors of VC.This prospective randomized intervention study assessed the impact of vitamin K2 supplementation on levels of the inactive form of MGP desphospho-uncarboxylated MGP (dp-ucMGP) in non-dialyzed 3 -5 stages CKD patients.Methods: Common carotid intima media thickness (CCA-IMT), coronary artery calcification score (CACS), serum mineral parameters, matrix Gla protein (MGP), desphospho-uncarboxylated MGP (dp-ucMGP), osteocalcin (OC) were measured at baseline and after 270±12 days of supplementation of 90 μg of vitamin K2 (menaquinone-7, MK-7) with 10 μg cholecalciferol (K+D group) or 10 μg vitamin D (group D) in 42 non-dialyzed CKD patients.Results: During the treatment period no significant changes of eGFR in both groups were observed.The significantly lower increase of CCA-IMT during the intervention period was noticed in group K+D: from 0.95±0.2mm at the beginning to 1.01±0.3mm, p=0.003 at the end, and in D group: from 1.02±0.2mm to 1.16±0.3mm, p=0.003.The change of CACS was numerically less in vitamin K+D treated patients than in D group (ΔCACS: 63.1±108.5 A.u. vs 74.4±127.1,p=0.7; 16% and 15.8%, p=0.91, respectively).After nine months of MK-7 supplementation a significant decrease of dp-ucMGP was found 1077.1±507.7 pmol/L vs 961.5±506.7,p=0.02.This effect was not observed in D group: 793.9±400.3pmol/L vs 820.7±565.2,p=0.7 respectively.The serum level of dp-ucMGP positively correlated with serum creatinine r=0.4,p=0,02, negatively with eGFR r=-0,5, p=0.003 at the beginning and r=0.4,p=0.03; r=-0.6,p=0.0001, respectively at the end of the study in both group.The positive correlation of dp-ucMGP and PTH level was noticed in all examined patients at the beginning and at the end of the study: r=0.4,p=0.04; r=0.4,p=0.01 respectively.Similar correlations were noticed between dp-ucMGP and OC: r=0.47, p=0.005; r=0.5; p=0.004 respectively.Any correlation between dp-ucMGP and estimated vascular changes was not find.Conclusions: The main determinant of dp-ucMGP level is the kidney function.Circulating level of dp-ucMGP may be a marker of vascular vitamin K status in CKD patients.The mechanisms by which vitamin K2 may exert the protective effect on progression of vessels damage are still uncertain, but may be connected with the impact of MK-7 on calcification's regulators, including the impact on the MGP carboxylation process.