The importance of klotho in phosphate metabolism and kidney disease

The discovery of fibroblast growth factor-23 (FGF23) and its co-receptor α-klotho has broadened our understanding of mineral metabolism and led to a renewed research focus on phosphate homeostatic pathways in kidney disease. Expanding knowledge of these mechanisms, both in normal physiology and in pathology, identifies targets for potential interventions designed to reduce the complications of renal disease, particularly the cardiovascular sequelae. FGF23 has emerged as a major α-klotho-dependent endocrine regulator of mineral metabolism, functioning to activate vitamin D and as a phosphatonin. However, increasingly there is an appreciation that klotho may act independently as a phosphate regulator, as well as having significant activity in other key biological processes. This review outlines our current understanding of klotho, and its potential contribution to kidney disease and cardiovascular health.