Kidney and phosphate metabolism

Abstract

The serum phosphorus level is maintained through a complex interplay between intestinal absorption, exchange intracellular and bone storage pools, and renal tubular reabsorption. The kidney plays a major role in regulation of phosphorus homeostasis by renal tubular reabsorption. Type IIa and type IIc Na(+)/Pi transporters are important renal Na(+)-dependent inorganic phosphate (Pi) transporters, which are expressed in the brush border membrane of proximal tubular cells. Both are regulated by dietary Pi intake, vitamin D, fibroblast growth factor 23 (FGF23) and parathyroid hormone. The expression of type IIa Na(+)/Pi transporter result from hypophosphatemia quickly. However, type IIc appears to act more slowly. Physiological and pathophysiological alteration in renal Pi reabsorption are related to altered brush border membrane expression/content of the type II Na(+)/Pi cotransporter. Many studies of genetic and acquired renal phosphate wasting disorders have led to the identification of novel genes. Two novel Pi regulating genes, PHEX and FGF23, play a role in the pathophysiology of genetic and acquired renal phosphate wasting disorders and studies are underway to define their mechanism on renal Pi regulation. In recent studies, sodium-hydrogen exchanger regulatory factor 1 (NHERF1) is reported as another new regulator for Pi reabsorption mechanism.

Keywords: PHEX; fibroblast growth factor 23; phosphorus; sodium-hydrogen exchanger regulatory factor 1; sodium-phosphate cotransporter proteins.

Fig. 1

Fibroblast growth factor 23 (FGF23)/klotho action. FGFR; FGF receptor; Type IIa/IIb/IIc Na/Pi, Type IIa/IIb/IIc Na⁺/Pi cotransporter; 24-OHase, 25-hydroxyvitamin D-24-hydroxylase; 1α-OHase, 25-hydroxyvitamin D-1α-hydroxylase.

Fig. 2

Phosphate Transport inhibition by parathyroid hormone (PTH) through sodium-hydrogen exchanger regulatory factor 1 (NHERF1) phosphorylation. PKA, protein kinase A; PKC, protein kinase C; NPT2, type II Na⁺/P_i cotransporter; PDZK1, PDZ domain containing 1 protein; PTH1R, PTH type 1 receptor.

Fig. 3

Pathophysiologic basis for X-linked hypophosphatemia (XLH). PHEX, Phosphate regulating gene with homologies to Endopeptidase, on the X chromosome; PTN, phosphatonin, PTNa, active PTN; PTNi, inactive phosphatonin; NPT2, type II Na⁺/Pi cotransporter.

Fig. 4

Pathophysiologic basis for tumor-induced osteomalacia (TIO). PHEX, Phosphate regulating gene with homologies to Endopeptidase, on the X chromosome; PTN, phosphatonin, PTNa, active PTN; PTNi, inactive phosphatonin; NPT2, type II Na⁺/Pi cotransporter.