For many years, the existence of "phosphatonins"--substances secreted by certain tumors which result in profound renal phosphorus wasting and resultant osteomalacia--has been postulated.
Evidence has recently been accumulating that fibroblast growth factor 23 (FGF-23) is the phosphatonin we have been searching for:
High circulating levels of FGF23 are associated with hypophosphatemia, decreased 1,25 (OH) vitamin D levels, and rickets/bone disease.
The disease autosomal dominant hypophosphatemic rickets is caused by gain-of-function mutations in FGF23caused by splice site mutations. Conversely, the genetic disease inherited tumoral calcinosis, characterized by hyperphosphatemia, increased 1,25 (OH) vitamin D levels, and metastatic calcifications.
In ESRD, FGF23 levels are appropriately elevated in response to hyperphosphatemia, but due to a reduced GFR is unable to induce adequate phosphaturia.
How it works at a molecular level: FGF23 interacts with FGF receptors at the proximal tubule, resulting in decreased Na-PO4 exchange, as well as decreasing 1,25-alpha hydroxylase activity.