Renal and Extrarenal Actions of Klotho

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

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Klotho is a single-pass transmembrane protein highly expressed in the kidney. Membrane Klotho protein acts as a co-receptor for fibroblast growth factor-23. Its extracellular domain is shed from the cell surface and functions as an endocrine substance that exerts multiple renal and extrarenal functions. An exhaustive review is beyond the scope and length of this article; thus, only effects with pertinence to mineral metabolism and renoprotection are highlighted here. Klotho participates in mineral homeostasis via interplay with other calciophosphoregulatory hormones (parathyroid hormone, fibroblast growth factor-23, and 1,25-[OH]2 vitamin D3) in kidney, bone, intestine, and parathyroid gland. Klotho also may be involved in acute and chronic kidney disease development and progression. Acute kidney injury is a temporary and reversible state of Klotho deficiency and chronic kidney disease is a sustained state of systemic Klotho deficiency. Klotho deficiency renders the kidney more susceptible to acute insults, delays kidney regeneration, and promotes renal fibrosis. In addition to direct renal effects, Klotho deficiency also triggers and aggravates deranged mineral metabolism, secondary hyperparathyroidism, vascular calcification, and cardiac hypertrophy and fibrosis. Although studies examining the therapeutic effect of Klotho replacement were performed in animal models, it is quite conceivable that supplementation of exogenous Klotho and/or up-regulation of endogenous Klotho production may be a viable therapeutic strategy for patients with acute or chronic kidney diseases.

Original languageEnglish (US)
Pages (from-to)118-129
Number of pages12
JournalSeminars in Nephrology
Volume33
Issue number2
DOIs
StatePublished - Mar 2013

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Kidney
Chronic Renal Insufficiency
Minerals
Fibrosis
Vascular Calcification
Fibroblast Growth Factor 1
Secondary Hyperparathyroidism
Parathyroid Glands
Cholecalciferol
Cardiomegaly
Therapeutic Uses
Parathyroid Hormone
Acute Kidney Injury
Intestines
Disease Progression
Regeneration
Membrane Proteins
Homeostasis
Up-Regulation
Animal Models

Keywords

  • Acute kidney injury
  • Cardiac hypertrophy
  • Chronic kidney disease
  • Hyperparathyroidism
  • Klotho

ASJC Scopus subject areas

  • Nephrology

Cite this

Renal and Extrarenal Actions of Klotho. / Hu, Ming C; Kuro-o, Makoto; Moe, Orson W.

In: Seminars in Nephrology, Vol. 33, No. 2, 03.2013, p. 118-129.

Research output: Contribution to journalArticle

Hu, Ming C ; Kuro-o, Makoto ; Moe, Orson W. / Renal and Extrarenal Actions of Klotho. In: Seminars in Nephrology. 2013 ; Vol. 33, No. 2. pp. 118-129.
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