Renal expression of FGF23 and peripheral resistance to elevated FGF23 in rodent models of polycystic kidney disease

Kidney Int. 2014 Jun;85(6):1340-50. doi: 10.1038/ki.2013.526. Epub 2014 Jan 8.


Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis and is linked to cardiovascular disease and all-cause mortality in chronic kidney disease. FGF23 rises in patients with CKD stages 2-3, but in patients with autosomal dominant polycystic kidney disease, the increase of FGF23 precedes the first measurable decline in renal function. The mechanisms governing FGF23 production and effects in kidney disease are largely unknown. Here we studied the relation between FGF23 and mineral homeostasis in two animal models of PKD. Plasma FGF23 levels were increased 10-fold in 4-week-old cy/+ Han:SPRD rats, whereas plasma urea and creatinine concentrations were similar to controls. Plasma calcium and phosphate levels as well as TmP/GFR were similar in PKD and control rats at all time points examined. Expression and activity of renal phosphate transporters, the vitamin D3-metabolizing enzymes, and the FGF23 co-ligand Klotho in the kidney were similar in PKD and control rats through 8 weeks of age, indicating resistance to FGF23, although phosphorylation of the FGF receptor substrate 2α protein was enhanced. In the kidneys of rats with PKD, FGF23 mRNA was highly expressed and FGF23 protein was detected in cells lining renal cysts. FGF23 expression in bone and spleen was similar in control rats and rats with PKD. Similarly, in an inducible Pkd1 knockout mouse model, plasma FGF23 levels were elevated, FGF23 was expressed in kidneys, but renal phosphate excretion was normal. Thus, the polycystic kidney produces FGF23 but is resistant to its action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Biomarkers / blood
  • Calcitriol / metabolism
  • Calcium / blood
  • Creatinine / blood
  • Disease Models, Animal
  • Female
  • Fibroblast Growth Factors / blood
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Glucuronidase / metabolism
  • Kidney / metabolism*
  • Kidney / pathology
  • Male
  • Mice, Knockout
  • Parathyroid Hormone / blood
  • Phosphates / blood
  • Phosphorylation
  • Polycystic Kidney Diseases / blood
  • Polycystic Kidney Diseases / genetics
  • Polycystic Kidney Diseases / metabolism*
  • Polycystic Kidney Diseases / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Signal Transduction
  • TRPP Cation Channels / deficiency
  • TRPP Cation Channels / genetics
  • Up-Regulation
  • Urea / blood


  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Fgf23 protein, rat
  • Parathyroid Hormone
  • Phosphates
  • RNA, Messenger
  • TRPP Cation Channels
  • fibroblast receptor substrate 2, rat
  • polycystic kidney disease 1 protein
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Urea
  • Creatinine
  • Glucuronidase
  • klotho protein
  • Calcitriol
  • Calcium