Elevated phosphate levels in CKD - a direct threat for the heart

Elevations in systemic phosphate levels, also called hyperphosphatemia, occur in chronic kidney disease (CKD) and during the normal aging process and are associated with various pathologies, such as cardiovascular injury. Experimental studies suggest that at high serum concentrations, phosphate can induce osteogenic differentiation of vascular smooth muscle cells and contribute to vascular calcification. However, the precise underlying mechanism leading to cardiovascular injury is not well understood. Here we discuss how elevations in extracellular phosphate levels could potentially affect cells and intracellular reactions and functions in general. We then zoom in on the heart to discuss whether hyperphosphatemia can have direct pathologic actions beyond inducing vascular calcification. Furthermore, we discuss myocardial calcification as a pathologic event that has not been described and studied in greater detail, but that seems to occur in the context of hyperphosphatemia-induced pathologic cardiac remodeling, as observed in dialysis patients.