Complement-mediated kidney diseases

Mol Immunol. 2020 Dec:128:175-187. doi: 10.1016/j.molimm.2020.10.015. Epub 2020 Nov 1.

Abstract

It has long been known that the complement cascade is activated in various forms of glomerulonephritis. In many of these diseases, immune-complexes deposit in the glomeruli and activate the classical pathway. Researchers have also identified additional mechanisms by which complement is activated in the kidney, including diseases in which the alternative and lectin pathways are activated. The kidney appears to be particularly susceptible to activation of the alternative pathway, and this pathway has been implicated as a primary driver of atypical hemolytic uremic syndrome, C3 glomerulopathy, anti-neutrophil cytoplasmic antibody-associated vasculitis, as well as some forms of immune-complex glomerulonephritis. In this paper we review the shared and distinct mechanisms by which complement is activated in these different diseases. We also review the opportunities for using therapeutic complement inhibitors to treat kidney diseases.

Keywords: Complement; Glomerulonephritis; Kidney; Therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology
  • Antigen-Antibody Complex / immunology
  • Atypical Hemolytic Uremic Syndrome / immunology
  • Complement Activation / immunology
  • Complement Inactivating Agents / immunology
  • Complement System Proteins / immunology*
  • Glomerulonephritis / immunology
  • Humans
  • Kidney / immunology
  • Kidney Diseases / immunology*

Substances

  • Antigen-Antibody Complex
  • Complement Inactivating Agents
  • Complement System Proteins