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  • Review Article
  • Published:

Novel targets of antifibrotic and anti-inflammatory treatment in CKD

Nature Reviews Nephrology volume 10, pages 257–267 (2014)Cite this article

Subjects

Key Points

  • The incidence of chronic kidney disease (CKD) has increased dramatically over the past 10 years, and new strategies for slowing its progression are urgently needed

  • Many novel approaches to control renal fibrosis in CKD are currently in clinical development

  • NADPH oxidase isoforms have emerged as important mediators of vascular dysfunction, inflammation, and fibrosis in CKD

  • New insights into the role of vascular calcification in the pathogenesis of CKD have led to novel therapeutic approaches, which are under preclinical and clinical development

  • Further animal studies and clinical trials are urgently needed to determine the potential beneficial effects of activating energy-sensing molecules in slowing the progression of CKD

  • Mitochondrial function and biogenesis are now considered as active players in the development of CKD

Abstract

Chronic kidney disease (CKD) is becoming a worldwide epidemic, driven largely by the dramatic rise in the prevalence of diabetes and obesity. Novel targets and treatments for CKD are, therefore, desperately needed—to both mitigate the burden of this disease in the general population and reduce the necessity for renal replacement therapy in individual patients. This Review highlights new insights into the mechanisms that contribute to CKD, and approaches that might facilitate the development of disease-arresting therapies for CKD. Particular focus is given to therapeutic approaches using antifibrotic agents that target the transforming growth factor β superfamily. In addition, we discuss new insights regarding the roles of vascular calcification, the NADPH oxidase family, and inflammation in the pathogenesis of CKD. We also highlight a new understanding regarding kidney energy sensing pathways (AMPK, sirtuins, and mTOR) in a variety of kidney diseases and how they are linked to inflammation and fibrosis. Finally, exciting new insights have been made into the role of mitochondrial function and mitochondrial biogenesis in relation to progressive kidney disease. Prospective therapeutics based on these findings will hopefully renew hope for clinicians and patients in the near future.

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Figure 1: Specific targets and potential therapeutic strategies to inhibit or slow the progression of CKD.

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Acknowledgements

K.S. is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK094352), the Veterans Administration Merit Grant (5101BX000277), and the Juvenile Diabetes Research Foundation.

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Authors and Affiliations

  1. Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles (ULB), CP603, 808 Route de Lennik, Brussels, 1070, Belgium

    Anne-Emilie Declèves

  2. Center for Renal Translational Medicine, University of California, San Diego and Veterans Affairs San Diego Healthcare System, Stein Clinical Research Building, 4th Floor, 9500 Gilman Drive, La Jolla, 92093-0711, CA, USA

    Kumar Sharma

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  1. Anne-Emilie Declèves
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A.-E.D. and K.S. contributed equally to researching the data for the article, discussions of its content, writing, reviewing and editing of the manuscript before submission.

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Correspondence to Kumar Sharma.

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Competing interests

K.S. has received research funding from AbbVie, has consulted for Boerhinger-Ingelheim, Genkyotex, and Sanofi, and holds equity in Clinical Metabolomics. A.-E.D. declares no competing interests.

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Declèves, AE., Sharma, K. Novel targets of antifibrotic and anti-inflammatory treatment in CKD. Nat Rev Nephrol 10, 257–267 (2014). https://doi.org/10.1038/nrneph.2014.31

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