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  • Review Article
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Renal fibrosis: novel insights into mechanisms and therapeutic targets

Nature Reviews Nephrology volume 6, pages 643–656 (2010)Cite this article

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This article has been updated

Abstract

Renal fibrosis is the common end point of virtually all progressive kidney diseases. Renal fibrosis should not be viewed as a simple and uniform 'scar', but rather as a dynamic system that involves extracellular matrix components and many, if not all, renal and infiltrating cell types. The involved cells exhibit enormous plasticity or phenotypic variability—a fact that we are only beginning to appreciate. Only a detailed understanding of the underlying mechanisms of renal fibrosis can facilitate the development of effective treatments. In this Review, we discuss the most recent advances in renal, or more specifically, tubulointerstitial fibrosis. Novel mechanisms as well as potential treatment targets based on different cell types are described. Problems that continue to plague the field are also discussed, including specific therapeutic targeting of the kidney, the development of improved diagnostic methods to assess renal fibrosis and the shortcomings of available animal models.

Key Points

  • Renal fibrosis is the common end point for all progressive renal diseases

  • This entity involves virtually all intrinsic and infiltrating cells and is characterized by alterations in their phenotype

  • Whether these alterations are part of a regenerative program or are largely pathological is still not clear

  • Many potential treatment targets for renal fibrosis have been identified in animal models

  • The lack of noninvasive diagnostic tools for renal fibrosis hinders efficient translation of these targets into clinical practice

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Figure 1: Histological features of renal fibrosis.
Figure 2: Immunohistochemical features of renal fibrosis in rats and mice 5 days after UUO.
Figure 3: PDGF regulation and signaling.
Figure 4: TGF-β modulation and signaling.

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Change history

  • 23 September 2010

    In the version of this article initially published online, there was a mistake in Figure 4. The errors have been corrected in all electronic versions of the text.

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Acknowledgements

We apologize to all authors whose important work could not be cited owing to space limitations. We wish to thank Dr B. Hintz and members of J. Floege's laboratory for valuable discussions. Our work described in this Review was supported by grants from the Deutsche Forschungsgemeinschaft (SFB/TRR 57), projects P14, P17 and P19 (to T. Ostendorf, J. Floege).

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  1. Department of Nephrology, RWTH University of Aachen, Pauwelsstrasse 30, Aachen, 52074, Germany

    Peter Boor, Tammo Ostendorf & Jürgen Floege

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  1. Peter Boor
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P. Boor wrote the manuscript; P. Boor, T. Ostendorf and J. Floege contributed equally to discussing content, and reviewing/editing the manuscript before submission.

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Correspondence to Jürgen Floege.

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J. Floege has received speaker honoraria and grant support from Amgen. P. Boor and T. Ostendorf declare no competing interests.

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Boor, P., Ostendorf, T. & Floege, J. Renal fibrosis: novel insights into mechanisms and therapeutic targets. Nat Rev Nephrol 6, 643–656 (2010). https://doi.org/10.1038/nrneph.2010.120

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