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Mechanisms of Disease: the complement system in renal injury—new ways of looking at an old foe

Nature Clinical Practice Nephrology volume 3, pages 277–286 (2007)Cite this article

Abstract

The fact that the complement system is activated during immune-complex glomerular disease has been known for nearly 50 years. Detection of complement deposition in the glomerulus using immunochemistry has become an important element of the histological analysis of renal biopsies, and is key to the diagnosis of many types of glomerulonephritis. In recent years it has become evident that complement activation is involved in the pathogenesis of other types of renal disease; complement activation is implicated in transplant injury, atypical hemolytic uremic syndrome and progressive tubulointerstitial fibrosis. Emergence of this evidence has provided insight into how these diseases develop, and has yielded useful diagnostic tools and potential targets for therapeutic intervention. Clinicians have, by using plasma-based therapies, unknowingly treated abnormalities of the complement system in renal patients for many years. Advances in antibody and protein technologies have led to the development of complement inhibitors that have been used in phase III clinical studies. More-specific agents and applications are likely to be developed over the coming years and are discussed in this Review.

Key Points

  • The majority of circulating complement is produced by the liver; complement synthesized in the kidney is likely to have an important role in local injury

  • Different pathways of complement activation are involved in different forms of renal disease, such as the alternative pathway in atypical hemolytic uremic syndrome and the classical pathway in lupus nephritis

  • Mutations of, deficiencies in, or autoantibodies against, complement proteins and their regulators have been detected in patients with, for example, atypical hemolytic uremic syndrome, lupus nephritis or membranoproliferative glomerulonephritis

  • Advances in antibody and protein technologies have led to the development of complement inhibitors that have been used in phase III clinical studies

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Figure 1: The complement activation cascade
Figure 2: Inhibitors of complement activation

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  1. KM Brown is a PhD student, SH Sacks is a Renal Physician, and NS Sheerin is a Clinical Senior Lecturer, at King's College London, London, UK.,

    Katherine M Brown, Steven H Sacks & Neil S Sheerin

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Correspondence to Neil S Sheerin.

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Brown, K., Sacks, S. & Sheerin, N. Mechanisms of Disease: the complement system in renal injury—new ways of looking at an old foe. Nat Rev Nephrol 3, 277–286 (2007). https://doi.org/10.1038/ncpneph0465

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