Can we reverse arterial stiffness by intervening on CKD-MBD biomarkers?

Abstract

The increased cardiovascular risk of chronic kidney disease may in part be the consequence of arterial stiffness, a typical feature of kidney failure. Deranged homeostasis of minerals and hormones involved (CKD-MBD), are also strongly associated with this increased risk. It is well established that CKD-MBD is a main driver of vascular calcification, which in turn worsens arterial stiffness. However, there are other contributors to arterial stiffness in CKD than calcification. An overlooked possibility is that CKD-MBD may have detrimental effects on this potentially better modifiable component of arterial stiffness. In this review, the individual contributions of short-term changes in calcium, phosphate, PTH, vitamin D, magnesium, and FGF23 to arterial stiffness, in most studies assessed as pulse wave velocity, is summarized. Indeed, there is evidence from both observational studies and interventional trials that higher calcium concentrations can worsen arterial stiffness. This, however, has not been shown for phosphate, and it seems unlikely that, apart from being a contributor to vascular calcification and having effects on the microcirculation, phosphate has no acute effect on large artery stiffness. Several interventional studies, both by infusing PTH and by abrupt lowering PTH by calcimimetics or surgery, virtually ruled out direct effects on large artery stiffness. A well-designed trial using both active and nutritional vitamin D as intervention found a beneficial effect for the latter. Unfortunately, the study had a baseline imbalance and other studies did not support its finding. Both magnesium and FGF23 do not seem do modify central arterial stiffness.