Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

The role of FGF23 in CKD-MBD (#5)

Seiji Fukumoto 1
  1. Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan

FGF23 is a phosphaturic hormone mainly produced by osteocytes. FGF23 suppresses proximal tubular phosphate reabsorption by reducing the expression of type 2a and 2c sodium phosphate cotransporters. FGF23 also decreases serum 1,25-dihydroxyvitamin D [1,25(OH)2D] by modulating the expression levels of vitamin D-metabolizing enzymes. While the affinity of FGF23 to FGF receptors is low, FGF23 can bind to Klotho-FGF receptor complex to transduce signals. Establishment of FGF23 assay indicated that excessive FGF23 actions cause several kinds of hypophosphatemic diseases such as X-linked hypophosphatemic rickets and tumor-induced osteomalacia. FGF23 is also high in patients with CKD. Especially, FGF23 can be extremely high in patients with end-stage renal disease. FGF23 starts to increase early during the progression of CKD. Several studies indicated that this increased FGF23 in early CKD enhances urinary phosphate excretion and works to prevent the development of hyperphosphatemia. At the same time, FGF23 reduces 1,25(OH)2D and seems to contribute to the development of secondary hyperparathyroidism. However, it is unknown what triggers the increase of FGF23 in early CKD. Many epidemiological studies indicated that high FGF23 levels are associated with various adverse events such as high mortality, cardiovascular events, left ventricular hypertrophy, and fractures especially in patients with CKD. It has also been shown that FGF23 can induce cardiac hypertrophy and neutrophil dysfunction in a Klotho-independent manner. However, it is not clear either how FGF23 can work in the absence of Klotho. In this symposium, I would like to discuss several unanswered questions about the role of FGF23 in CKD-MBD.