Phosphorus, abundant in most diets, is a key structural component of DNA, RNA, phosphoproteins, and phospholipids, all essential biomolecules to ensure cell viability and function. Consequently, normal phosphorus maintains the functional integrity of all tissues. However, high dietary phosphorus induces proinflammatory, pro-aging features that markedly reduce survival in the general population and in chronic kidney disease (CKD) patients. High phosphorus downregulation of the renal content of the longevity molecule α-klotho is a main determinant of the severe mineral, renal, and cardiovascular disturbances increasing mortality rates. High phosphorus inhibition of renal calcitriol production, an inducer of α-Klotho gene expression, further aggravates the high mortality rates associated with hyperphosphatemia. Indeed, dietary phosphorus restriction, an inducer of renal calcitriol production, effectively counteracts hyperphosphatemia adverse effects on survival. Calcitriol efficacy to induce both renal α-Klotho and bone synthesis of the phosphaturic hormone fibroblast growth factor-23 (FGF23), while tightly suppressing its own renal production to reduce intestinal calcium and phosphorus absorption and, consequently, the risk of hypercalcemia and hyperphosphatemia, is essential to improve survival. This chapter updates the molecular mechanisms mediating (1) the opposing regulation of renal calcitriol production by high and low dietary phosphorus; (2) the antagonistic interactions between high phosphorus and the vitamin D system that maintain the phosphorus/calcitriol/FGF23- α-Klotho axis essential for survival; (3) the abnormalities in this critical axis induced by CKD; and (4) the synergistic interactions between 25-hydroxyvitamin D [25(OH)D] and calcitriol to enhance renal α-Klotho and bone FGF23 expression, which could explain the survival benefits associated with a normal vitamin D status.
|Title of host publication||Dietary Phosphorus|
|Subtitle of host publication||Health, Nutrition, and Regulatory Aspects|
|Number of pages||11|
|State||Published - Jan 1 2017|