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. Author manuscript; available in PMC: 2016 Oct 25.
Published in final edited form as: Semin Nephrol. 2013 Mar;33(2):130–142. doi: 10.1016/j.semnephrol.2012.12.014

Figure 1.

Figure 1

Endocrine networks involved in the pathogenesis of CKD mineral and bone disease. (A) PTH–vitamin D axis. PTH secreted by the parathyroid glands under control of the CaSR directly targets PTHR1 in bone and kidney to stimulate, respectively, calcium efflux from bone, renal conservation of calcium and production of 1,25(OH)2D, the latter targets VDR in intestines to increase calcium absorption as well as in other tissues to regulate multiple cellular functions. PTH also has phosphaturic actions on the kidney and in certain settings also stimulates FGF23 and Ocn secretion from bone. (B) FGF23–bone-kidney axis. FGF23 is secreted by osteoblasts/osteocytes in bone under control of multiple factors, including 1,25(OH)2D, leptin, glucocorticoids, PTH, and bone mineralization/turnover. Circulating FGF23 targets FGFR/α-Klotho complexes located in the kidney, pituitary, thymus, and parathyroid glands. The principal biological actions of FGF23 are to suppress circulating 1,25(OH)2D levels, owing to combined actions to decrease Cyp27b1-mediated synthesis and possibly stimulation of Cyp24-mediated degradation of this active vitamin D sterol, and to inhibit the renal reabsorption of phosphate leading to phosphaturia. FGF23 also may suppress PTH secretion. In addition, direct effects of FGF23 on FGFR pathways in the absence of the co-receptor α-Klotho have been proposed.