Phosphate and cardiovascular disease.

Hyperphosphatemia is a major risk factor for death, CVE, and vascular calcification among patients with and without kidney disease. Even serum phosphate levels within the "normal laboratory range" associate with a greater risk of death and CVE. Potential mechanisms by which increased phosphate results in adverse outcomes are not fully understood, but current evidence suggests a direct effect of phosphate on vascular calcification and modulation of key hormones fibroblast growth factor-23 and calcitriol. Despite convincing epidemiologic connections between phosphate excess and cardiovascular disease, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy.