Fibroblast Growth Factor 23 and Klotho in AKI

Semin Nephrol. 2019 Jan;39(1):57-75. doi: 10.1016/j.semnephrol.2018.10.005.

Abstract

Acute kidney injury (AKI) is associated with many of the same mineral metabolite abnormalities that are observed in chronic kidney disease. These include increased circulating levels of the osteocyte-derived, vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23), and decreased renal expression of klotho, the co-receptor for FGF23. Recent data have indicated that increased FGF23 and decreased klotho levels in the blood and urine could serve as novel predictive biomarkers of incident AKI, or as novel prognostic biomarkers of adverse outcomes in patients with established AKI. In addition, because FGF23 and klotho exert numerous classic as well as off-target effects on a variety of organ systems, targeting their dysregulation in AKI may represent a unique opportunity for therapeutic intervention. We review the pathophysiology, kinetics, and regulation of FGF23 and klotho in animal and human studies of AKI, and we discuss the challenges and opportunities involved in targeting FGF23 and klotho therapeutically.

Keywords: AKI; FGF23; klotho; mineral metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / therapy
  • Animals
  • Biomarkers / blood
  • Cardiac Surgical Procedures / adverse effects
  • Critical Illness
  • Fibroblast Growth Factors / antagonists & inhibitors
  • Fibroblast Growth Factors / blood
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / physiology
  • Fibrosis
  • Glucuronidase / genetics
  • Glucuronidase / metabolism*
  • Glucuronidase / physiology
  • Glucuronidase / therapeutic use
  • Humans
  • Kidney / pathology*
  • Prognosis
  • Renal Insufficiency, Chronic / blood
  • Severity of Illness Index
  • Signal Transduction

Substances

  • Biomarkers
  • Fgf23 protein, rat
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Glucuronidase
  • klotho protein