Klotho and kidney disease

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

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Klotho is a single-pass transmembrane protein that exerts its biological functions through multiple modes. Membrane-bound Klotho acts as coreceptor for the major phosphatonin fibroblast growth factor-23 (FGF23), while soluble Klotho functions as an endocrine substance. In addition to in the distal nephron where it is abundantly expressed, Klotho is present in the proximal tubule lumen where it inhibits renal Pi excretion by modulating Na-coupled Pi transporters via enzymatic glycan modification of the transporter proteins - an effect completely independent of its role as the FGF23 coreceptor. Acute kidney injury (AKI) and chronic kidney disease (CKD) are states of systemic Klotho deficiency, making Klotho a very sensitive biomarker of impaired renal function. In addition to its role as a marker, Klotho also plays pathogenic roles in renal disease. Klotho deficiency exacerbates decreases in, while Klotho repletion or excess preserves, glomerular filtration rate in both AKI and CKD. Soft tissue calcification, and especially vascular calcification, is a dire complication in CKD, associated with high mortality. Klotho protects against soft tissue calcification via at least 3 mechanisms: phosphaturia, preservation of renal function and a direct effect on vascular smooth muscle cells by inhibiting phosphate uptake and dedifferentiation. In summary, Klotho is a critical molecule in a wide variety of renal diseases and bears great potential as a diagnostic and prognostic biomarker as well as for therapeutic replacement therapy.

Original languageEnglish (US)
JournalJournal of Nephrology
Volume23
Issue numberSUPPL.16
StatePublished - 2010

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Kidney Diseases
Chronic Renal Insufficiency
Kidney
Acute Kidney Injury
Biomarkers
Familial Hypophosphatemia
Vascular Calcification
Nephrons
Glomerular Filtration Rate
Vascular Smooth Muscle
Smooth Muscle Myocytes
Polysaccharides
Proteins
Phosphates
Membranes
Mortality
Therapeutics
fibroblast growth factor 23

Keywords

  • Acute kidney injury
  • Chronic kidney disease
  • Klotho
  • Phosphaturia
  • Vascular calcification

ASJC Scopus subject areas

  • Nephrology

Cite this

Klotho and kidney disease. / Hu, Ming C; Kuro-o, Makoto; Moe, Orson W.

In: Journal of Nephrology, Vol. 23, No. SUPPL.16, 2010.

Research output: Contribution to journalArticle

Hu, MC, Kuro-o, M & Moe, OW 2010, 'Klotho and kidney disease', Journal of Nephrology, vol. 23, no. SUPPL.16.
Hu, Ming C ; Kuro-o, Makoto ; Moe, Orson W. / Klotho and kidney disease. In: Journal of Nephrology. 2010 ; Vol. 23, No. SUPPL.16.
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