The emerging role of Klotho in clinical nephrology

Ming C Hu, Makoto Kuro-o, Orson W Moe

Research output: Contribution to journalReview articlepeer-review

115 Scopus citations


Klotho is highly expressed in the kidney and a soluble form of Klotho functions as an endocrine substance that exerts multiple actions including the modulation of renal solute transport and the protection of the kidney from a variety of insults in experimental models. At present, the Klotho database is still largely preclinical, but the anticipated forthcoming impact on clinical nephrology can be immense. This manuscript puts these potentials into perspective for the clinician. There is renal and systemic Klotho deficiency in both acute kidney injury (AKI) and chronic kidney disease (CKD). Klotho plummets very early and severely in AKI and represents a pathogenic factor that exacerbates acute kidney damage. In CKD, Klotho deficiency exerts a significant impact on progression of renal disease and extra renal complications. In AKI, soluble Klotho levels in plasma and/or urine may serve as an early biomarker for kidney parenchymal injury. Restoration by exogenous supplementation or stimulation of endogenous Klotho may prevent and/or ameliorate kidney injury and mitigate CKD development. In CKD, Klotho levels may be an indicator of early disease and predict the rate of progression, and presence and severity of soft tissue calcification. The correction of Klotho deficiency may delay progression and forestall development of extra renal complications in CKD. Rarely does one find a molecule with such broad potential applications in nephrology. Klotho can possibly emerge on the horizon as a candidate for an unprecedented sole biomarker and intervention. Nephrologists should monitor the progress of the preclinical studies and the imminently emerging human database.

Original languageEnglish (US)
Pages (from-to)2650-2657
Number of pages8
JournalNephrology Dialysis Transplantation
Issue number7
StatePublished - Jul 2012


  • FGF23
  • Klotho
  • acute kidney injury
  • biomarker
  • cardiac hypertrophy
  • chronic kidney disease
  • prognosis
  • secondary hyperparathyroidism

ASJC Scopus subject areas

  • Nephrology
  • Transplantation


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