Phosphorus and Kidney Disease: Mechanisms for Perturbed Phosphorus Homeostasis in Chronic Kidney Disease

Abnormalities in phosphorus metabolism occur early in chronic kidney disease (CKD). Compensatory changes in renal phosphate handling are sufficient to maintain serum phosphorus within the normal laboratory range in early stages of kidney disease, but in more advanced kidney disease, these mechanisms no longer suffice and hyperphosphatemia ensues. Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are the main phosphaturic hormones that increase renal phosphate excretion by decreasing the renal sodium-phosphate cotransporters in the proximal tubule. FGF23 increases renal phosphate excretion earlier than PTH in response to abnormal phosphate homeostasis, and together elevations in FGF23 and PTH mediate processes that help restore serum phosphorus levels to normal in moderate-to-severe CKD. FGF23 is modulated by dietary phosphorus intake, 1,25-dihydroxyvitamin D (1,25(OH)2D), and PTH. FGF23 synthesis and release are positively regulated by serum phosphorus and 1,25(OH)2D and negatively regulated by unknown mechanisms. The major focus of this chapter will be to understand the mechanism of abnormal phosphorus homeostasis in patients with kidney disease, with particular attention to the biochemical/hormonal factors including vitamin D, PTH, and FGF23, as well as a brief consideration of bone and the intestine.