Circulating dp-ucMGP is Associated with Kidney Dysfunction and Arterial Stiffness (Puzantian et al.)
The American Journal of Hypertension is publishing a recently completed trial that examined chronic kidney disease (CKD) patients, a population prone to increased large artery stiffening, to identify pathways related to arterial stiffness in earlier CKD stages. The end goal was to provide insight on opportunities for novel therapeutic strategies to ameliorate the arterial stiffness and calcification process of vascular calcification. The results showed this population had high levels of inactive Matrix Gla Protein (dp-ucMGP). MGP is the most potent inhibitor of vascular calcification known to date, provided the body has enough Vitamin K2 to activate it.
Large artery stiffening is increased in advanced CKD and is thought to causally mediate various cardiovascular complications of CKD. Carotid-femoral pulse wave velocity (CF-PWV), the non-invasive gold-standard measure of large artery stiffness, is strongly associated with increased mortality in advanced CKD.
The identification of pathways related to arterial stiffness in earlier CKD stages may provide opportunities for novel therapeutic strategies to ameliorate the arterial stiffness and calcification process in CKD.
Matrix Gla-Protein (MGP) is a vitamin K dependent protein. The inactive form of MGP (dephospho-uncarboxylated MGP, dp-ucMGP) is a recognized marker of vitamin K status, and active matrix Gla-Protein (MGP) is a potent vitamin-K dependent inhibitor of vascular calcification.
The aim of the study was to establish the relationship between renal dysfunction and the circulating levels of dpucMGP (inactive MGP), and to assess the relationship between dp-ucMGP and carotid-femoral pulse wave velocity (CF-PWV), the gold standard non-invasive measure of large artery stiffness.
Researchers enrolled 137 adults without HF with varying degrees of renal function: normal eGFR (>90 mL/min; n=59), mildly reduced eGFR (stage 2 CKD: eGFR = 60-89 mL/min; n=53) or at least moderately reduced eGFR (stage 3-5 CKD; eGFR).
The authors found that lower kidney function is independently associated with greater levels of plasma dp-ucMGP. In addition, they demonstrated that greater levels of dp-ucMGP are independently associated with increased CF-PWV (a measure of large artery stiffness), but not with carotid-radial PWV (a measure of muscular artery stiffness). They further demonstrate that dp-ucMGP levels mediate a significant relationship between eGFR and higher CF-PWV, whereas no significant dp-ucMGP-independent relationship was present.
According to the researchers, “These findings should stimulate further studies on dp-ucMGP and trials with vitamin K supplementation in early CKD, to assess whether this intervention can ameliorate the marked, progressive large artery stiffening that occurs with progression to end-stage renal disease.”
“Based on the finished and ongoing clinical trials, vitamin K2 as MK-7 seems to be the most promising form of vitamin K, which should be beneficial for kidney patients,” explains Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “Vitamin K2 treatment in kidney patients was shown to not only improve vitamin K status but also was may reduce the progression of atherosclerosis.”
Puzantian H et al. Circulating dp-ucMGP is associated with kidney dysfunction and arterial stiffness. Am J Hypertens. 2018 May 17. Doi: 10.1093/ajh/hpy079.