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Klotho in Clinical Nephrology

Diagnostic and Therapeutic Implications

Javier A. Neyra, Ming Chang Hu and Orson W. Moe
CJASN January 2021, 16 (1) 162-176; DOI: https://doi.org/10.2215/CJN.02840320
Javier A. Neyra
1Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, Dallas, Texas
2Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
3Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky
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Ming Chang Hu
1Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, Dallas, Texas
2Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
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Orson W. Moe
1Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, Dallas, Texas
2Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
4Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas
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Abstract

αKlotho (called Klotho here) is a membrane protein that serves as the coreceptor for the circulating hormone fibroblast growth factor 23 (FGF23). Klotho is also cleaved and released as a circulating substance originating primarily from the kidney and exerts a myriad of housekeeping functions in just about every organ. The vital role of Klotho is shown by the multiorgan failure with genetic deletion in rodents, with certain features reminiscent of human disease. The most common causes of systemic Klotho deficiency are AKI and CKD. Preclinical data on Klotho biology have advanced considerably and demonstrated its potential diagnostic and therapeutic value; however, multiple knowledge gaps exist in the regulation of Klotho expression, release, and metabolism; its target organs; and mechanisms of action. In the translational and clinical fronts, progress has been more modest. Nonetheless, Klotho has potential clinical applications in the diagnosis of AKI and CKD, in prognosis of progression and extrarenal complications, and finally, as replacement therapy for systemic Klotho deficiency. The overall effect of Klotho in clinical nephrology requires further technical advances and additional large prospective human studies.

  • Klotho;
  • nephrology;
  • kidney;
  • diagnosis;
  • therapy
  • Copyright © 2021 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 16 (1)
Clinical Journal of the American Society of Nephrology
Vol. 16, Issue 1
January 07, 2021
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Klotho in Clinical Nephrology
Javier A. Neyra, Ming Chang Hu, Orson W. Moe
CJASN Jan 2021, 16 (1) 162-176; DOI: 10.2215/CJN.02840320

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Klotho in Clinical Nephrology
Javier A. Neyra, Ming Chang Hu, Orson W. Moe
CJASN Jan 2021, 16 (1) 162-176; DOI: 10.2215/CJN.02840320
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  • Article
    • Abstract
    • Introduction
    • Physiology of Klotho
    • Klotho in Disease States
    • Potential Mechanisms of Klotho-Mediated Kidney and Cardiovascular Protection
    • Biomarker Candidacy in Human Kidney Disease
    • Measurement of Soluble Klotho in Humans
    • Klotho-Focused Therapies
    • Summary and Call for Action
    • Disclosures
    • Funding
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More in this TOC Section

  • Decision Algorithm for Prescribing SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney Disease
  • Cuffless Blood Pressure Monitoring
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Keywords

  • Klotho;
  • nephrology;
  • kidney;
  • diagnosis;
  • therapy

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