Fibroblast Growth Factor 23

Cardiovascular disease (CVD) and the associated rhythm abnormalities manifesting as tachyarrhythmias, such as atrial fibrillation (AF), continue as leading causes of morbidity and mortality in the United States and developed countries.1 In spite of the exciting momentum of new discoveries that have greatly improved our understanding of several key molecular mechanisms underlying AF, identifying and managing AF during its early onset stage is extremely challenging.2 Traditionally, direct causes for CVD have been attributed primarily to genes, ischemic heart disease, poor dietary choices, and lack of exercise; studies later revealed that diseases such as high blood pressure, diabetes mellitus, obesity, and chronic kidney disease (CKD) are powerful risk factors that can equally impact the heart and cause pathologic structural remodeling, contractile dysfunction, hypertrophy, and heart failure, which are well-established substrates for AF.3Article see p 298Of these, CKD has emerged as one of the most potent risk factors for developing CVD and particularly AF. In fact, the high rates of mortality reported in patients with CKD are mainly attributed to cardiovascular complications, including uremic cardiomyopathy or vascular calcifications leading to cardiac complications.4 Although the reciprocal cross-talk between dysfunctions of kidney and heart is well known, very few common mechanisms have been conclusively identified that could be targeted to impact both CKD and CVD. In this context, fibroblast growth factor 23 (FGF23), a recently described phosphate-regulating hormone secreted by osteocytes and osteoblasts, draws attention. FGF23 works via fibroblast growth factor receptors or specialized Klotho receptors to reduce gastrointestinal phosphate absorption5 and stimulate renal phosphate elimination.6 Its expression is positively linked to CKD, wherein FGF23 levels increase during the early stages of CKD and are believed to play a role in increasing urinary phosphate excretion. Elevated FGF23 levels are also associated with the progression of kidney …