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  • Review Article
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Potential approaches to reverse or repair renal fibrosis

Nature Reviews Nephrology volume 10, pages 226–237 (2014)Cite this article

Subjects

Key Points

  • On the basis of promising preclinical and clinical data, the fatalistic concept of the 'point of no return' in chronic kidney disease (CKD) must be revised; evidence supports that CKD can be reversed

  • As fibrosis is controlled by overlapping pathways across all organs, the vast pipeline of antifibrotic drugs in preclinical and clinical development might be of benefit to patients with CKD in the future

  • Ongoing clinical trials to ameliorate fibrosis in the kidney are assessing transforming growth factor-β1 inhibitors, connective tissue growth factor inhibitors, bone morphogenic protein-7 agonists and endothelin-1 antagonists

  • Other strategies are exploring blockade of CC chemokine receptor type 2 and phosphodiesterase type 5 inhibition

Abstract

The concept of reversing chronic kidney disease (CKD) has been intensively researched over the past decade. Indeed, as the prevalence of end-stage renal disease is constantly on the rise, the lack of established antifibrotic therapies is a considerable unmet need in clinical practice. Now, the possibility of effective antifibrotic treatment has been established in experimental models of CKD and multiple antifibrotic compounds—in kidney disease, as well as in fibrotic diseases of the skin, liver and lung—are being assessed in clinical trials. These strategies target various components of the fibrotic pathway, from signalling molecules that include transforming growth factor-β, phosphatidylinositide 3-kinase and chemokines to microRNAs. Here, we discuss therapeutic concepts to inhibit or even reverse chronic kidney injury and review the leading candidate antifibrotic drugs to be introduced to clinical use.

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Figure 1: Overview of different antifibrotic strategies.
Figure 2: Agents that target the TGF-β and BMP-7 signalling pathways.

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Acknowledgements

M.Z. is supported by German Research Foundation (DFG) grants ZE523/2-1 and ZE523/3-1.

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  1. Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert Koch Straße 40, Göttingen, 37075, Germany

    Desiree Tampe & Michael Zeisberg

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Tampe, D., Zeisberg, M. Potential approaches to reverse or repair renal fibrosis. Nat Rev Nephrol 10, 226–237 (2014). https://doi.org/10.1038/nrneph.2014.14

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