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  • Review Article
  • Published:

Immune system modulation of kidney regeneration—mechanisms and implications

Nature Reviews Nephrology volume 10, pages 347–358 (2014)Cite this article

Subjects

Key Points

  • Inflammation and regeneration are tightly interlinked danger response programmes

  • The regenerative capacity of tissues is limited by cell necrosis, which triggers inflammation via release of damage-associated molecular patterns

  • The regenerative capacity of the kidney enables recovery from transient renal diseases; however, repetitive or persistent injuries and ongoing inflammation impair regeneration and promote tissue atrophy

  • As nephrons are independent structures, kidney disease outcomes depend on the balance between injury and inflammation as well as the intrinsic regenerative capacity of each individual nephron

  • Monocytic phagocyte and lymphocyte phenotypes are important determinants of humoral microenvironments, which determine the balance of proinflammatory and proregenerative mediators in the kidney

  • A three-step therapeutic approach involving removal of the injurious trigger, suppression of renal inflammation and enhancement of regenerative mechanisms could potentially improve outcomes of kidney disease

Abstract

The immune system is an important guardian of tissue homeostasis. In response to injury, resident and infiltrating immune cells orchestrate all phases of danger control, resolution of inflammation and tissue regeneration or scar formation. As mammalian postnatal kidneys are not capable of de novo nephrogenesis, recovery is limited to the regeneration or repair of existing nephrons. The regenerative capacity of the nephron varies between compartments; the epithelial cells of the tubule regenerate more efficiently than the structurally highly organized podocytes. Cells of the surrounding environment modulate nephron regeneration by secreting paracrine mediators. This Review discusses immune mediators and pathways that regulate the intrinsic regenerative capacity of the nephron. Eliminating injurious triggers, modulating renal inflammation and specifically enhancing the regenerative capacity of nephrons might be a promising strategy to improve long-term outcomes in patients with acute kidney injury and/or chronic kidney disease.

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Figure 1: Long-term outcomes in kidney disease depend on the transient or persistent nature of the injurious trigger.
Figure 2: Intrarenal immune cells modulate tubule regeneration.

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Acknowledgements

The author's work is supported by grants from the Deutsche Forschungsgemeinschaft (AN372/9-2, AN371/12-2 and AN372/15-1) and the Else Kröner-Fresenius Stiftung (2011_A95). The author thanks Jyaysi Desai and Simone Romoli for their help in preparing figures and tables.

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  1. Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München-Innenstadt, Ziemssenstrasse 1, Munich, 80336, Germany

    Hans-Joachim Anders

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Supplementary Table 1

Definitions of terms related to inflammation and regeneration. (DOC 46 kb)

Supplementary Table 2

Effect of inflammatory mediators on proliferation of progenitor cells. (DOC 89 kb)

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Anders, HJ. Immune system modulation of kidney regeneration—mechanisms and implications. Nat Rev Nephrol 10, 347–358 (2014). https://doi.org/10.1038/nrneph.2014.68

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