Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Oct 22;19(1):285.
doi: 10.1186/s12882-018-1094-z.

The role of klotho in chronic kidney disease

Di Zou  1 , Wen Wu  2 , Yan He  1 , Sichao Ma  1 , Ji Gao  3
Affiliations
Review

The role of klotho in chronic kidney disease

Di Zou et al. BMC Nephrol. .

Abstract

Chronic kidney disease (CKD) is an inherently systemic disease that refers to a long-term loss of kidney function. The progression of CKD has repercussions for other organs, leading to many kinds of extrarenal complications. Intensive studies are now being undertaken to reveal the risk factors and pathophysiological mechanism of this disease. During the past 20 years, increasing evidence from clinical and basic studies has indicated that klotho, which was initially known as an anti-aging gene and is mainly expressed in the kidney, is significantly correlated with the development and progression of CKD and its complications. Here, we discuss in detail the role and pathophysiological implications of klotho in ion disorders, the inflammation response, vascular calcification, mineral bone disorders, and renal fibrosis in CKD. Based on the pathogenic mechanism of klotho deficiency and klotho decline in urine early in CKD stage 2 and even earlier in CKD stage 1, it is not difficult to understand that soluble klotho can serve as an early and sensitive marker of CKD. Moreover, the prevention of klotho decline by several mechanisms can attenuate renal injuries, retard CKD progression, ameliorate extrarenal complications, and improve renal function. In this review, we focus on the functions and pathophysiological implications of klotho in CKD and its extrarenal complications as well as its potential applications as a diagnostic and/or prognostic biomarker for CKD and as a novel treatment strategy to improve and decrease the burden of comorbidity in CKD.

Keywords: Chronic kidney disease; Extrarenal complications; Klotho functions; Pathogenic mechanism; Potential applications.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The structure of the klotho gene and protein. a The structure of the klotho genes from humans and mice. b The structure of the klotho protein. Soluble klotho proteins are generated by full-length transcript splicing at the indicated α and β cut sites, comprising the entire extracellular domain, or at the single Kl1 or Kl2 domains
See this image and copyright information in PMC

References

    1. Hu MC, Shi M, Gillings N, Flores B, Takahashi M, Kuro OM, Moe OW. Recombinant alpha-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy. Kidney Int. 2017;91(5):1104–1114. doi: 10.1016/j.kint.2016.10.034. - DOI - PMC - PubMed
    1. Zoja C, Abbate M, Remuzzi G. Progression of chronic kidney disease: insights from animal models. Curr Opin Nephrol Hypertens. 2006;15(3):250–257. doi: 10.1097/01.mnh.0000222691.53970.83. - DOI - PubMed
    1. Cortinovis M, Ruggenenti P, Remuzzi G. Progression, Remission and Regression of Chronic Renal Diseases. Nephron. 2016;134(1):20–24. doi: 10.1159/000445844. - DOI - PubMed
    1. Hu MC, Kuro-o M, Moe OW. Klotho and chronic kidney disease. Contrib Nephrol. 2013;180:47–63. doi: 10.1159/000346778. - DOI - PMC - PubMed
    1. Giachelli CM. The emerging role of phosphate in vascular calcification. Kidney Int. 2009;75(9):890–897. doi: 10.1038/ki.2008.644. - DOI - PMC - PubMed

MeSH terms