| [ Summary ] |
The association between abnormal phosphorus levels and cardiovascular conditions has been well established in populations with advanced chronic kidney disease (CKD). These findings have recently been extended to include phosphorus being levels within normal ranges. This is accomplished with a retrospective analysis of individuals who have had previous myocardial infarctions but are adults who have no cardiovascular disease. Potential mechanisms to link elevated phosphorus levels to vascular disease include an increase in fibroblast growth factor 23 (FGF23) levels, inhibition of 1,25-dihydroxyvitamin D synthesis and increased parathyroid hormone (PTH) production. FGF23 is a recently discovered phosphateregulating hormone largely produced by osteocytes in response to hyperphosphatemia which exerts its effects on receptors. This receptor is the Klotho-FGFR1c heterodimer. In the kidney it inhibits the expression of Na-Pi cotransporters resulting in hyperphosphaturia. Several observational studies have demonstrated the association between FGF23 levels and clinical outcomes in both dialysis patients and the general population. This association suggests that FGF23 may play a role in conferring cardiovascular risk on CKD patients, independent of its role in renal phosphate reabsorption. Serum FGF23 levels are associated with left ventricular hypertrophy, which has an important prognostic value for CKD patients. Experimental studies have shown that FGF23 directly induces cardiac hypertrophy in a Klotho-independent manner. However, further research is required to address the question of whether FGF23 plays a causative role in vascular calcification and atherosclerosis. |