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Inflammatory processes in renal fibrosis

Nature Reviews Nephrology volume 10, pages 493–503 (2014)Cite this article

Subjects

Key Points

  • Renal inflammation is a protective response that is induced following kidney injury, which seeks to eliminate the cause of injury and establish tissue repair

  • In the absence of resolution, ongoing inflammation involving infiltrating leukocytes in conjunction with activation of intrinsic renal cells results in the production of profibrotic cytokines and growth factors

  • These profibrotic cytokines and growth factors, in turn, recruit and activate myofibroblasts, which cause progressive glomerular and interstitial fibrosis, leading to end-stage renal disease

  • Glomerular and interstitial fibrosis occur sequentially and share a number of common pathogenetic mechanisms, but the link between glomerular inflammation and interstitial fibrosis is poorly understood

  • Macrophages drive fibrosis during ongoing kidney, injury but have the capacity to promote renal repair when the underlying injury can be resolved

Abstract

Many types of kidney injury induce inflammation as a protective response. However, unresolved inflammation promotes progressive renal fibrosis, which can culminate in end-stage renal disease. Kidney inflammation involves cells of the immune system as well as activation of intrinsic renal cells, with the consequent production and release of profibrotic cytokines and growth factors that drive the fibrotic process. In glomerular diseases, the development of glomerular inflammation precedes interstitial fibrosis; although the mechanisms linking these events are poorly understood, an important role for tubular epithelial cells in mediating this link is gaining support. Data have implicated macrophages in promoting both glomerular and interstitial fibrosis, whereas limited evidence suggests that CD4+ T cells and mast cells are involved in interstitial fibrosis. However, macrophages can also promote renal repair when the cause of renal injury can be resolved, highlighting their plasticity. Understanding the mechanisms by which inflammation drives renal fibrosis is necessary to facilitate the development of therapeutics to halt the progression of chronic kidney disease.

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Figure 1: Evidence for local macrophage accumulation and renal fibrosis.
Figure 2: The role of macrophages in renal fibrosis.
Figure 3: Tubular cell activation in interstitial inflammation and fibrosis.

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Acknowledgements

We apologize to all colleagues whose important findings could not be cited owing to space limitations. This work was supported by the Major State Basic Research Program of China, 973 programme (2012CB517700), the Research Grant Council of Hong Kong grants (RGC GRF 469110, N_CUHK40410, 468711, CUHK5/CRF/09 and CUHK3/CRF/12R), the Focused Investment Scheme A and B from the Chinese University of Hong Kong and the National Natural Science Foundation of China (No. 81300580).

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Authors and Affiliations

  1. School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China

    Xiao-Ming Meng

  2. Monash University Department of Medicine, 246 Clayton Road, Clayton, Melbourne, 3168, Vic, Australia

    David J. Nikolic-Paterson

  3. Li Ka Shing Institute of Health Sciences and Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, Shatin

    Hui Yao Lan

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X.-M.M. researched data for the article. All authors discussed the article's content, after which X.-M.M. wrote the manuscript; D.J.N.-P. and H.Y.L. reviewed and edited the manuscript before submission.

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Correspondence to Hui Yao Lan.

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Competing interests

David J. Nikolic-Paterson has previously worked as a consultant and received research funding from Celgene, and has previously worked as a consultant for Johnson & Johnson Pharmaceuticals. The other authors declare no competing interests.

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Meng, XM., Nikolic-Paterson, D. & Lan, H. Inflammatory processes in renal fibrosis. Nat Rev Nephrol 10, 493–503 (2014). https://doi.org/10.1038/nrneph.2014.114

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