The etiology of glomerulonephritis: roles of infection and autoimmunity

Kidney Int. 2014 Nov;86(5):905-14. doi: 10.1038/ki.2014.49. Epub 2014 Mar 12.


Despite major advances in understanding genetic predispositions ('first hits'), pathogenic immune responses, and the mediators of tissue injury in glomerulonephritis (GN), there remains a dearth of knowledge about the etiologic events, or 'second hits', which trigger these diseases. This paper reviews evidence that infections initiate most forms of GN through numerous simultaneous and/or sequential pathways that begin with activation of the innate immune response and lead to autoimmunity. These pathways include immune dysregulation, adjuvant or bystander effects, epitope spreading, molecular mimicry, epitope conformational changes, and antigen complementarity that, in genetically susceptible individuals, result in the nephritogenic autoimmune responses that underlie GN. Infections may also have direct effects on glomerular cells. Rapid expansion in knowledge of the microbiome and its role in health and disease, as well as systems biology approaches to glomerular disease offer the potential to develop preventive approaches to GNs that can now be treated only with immunosuppression.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Bacterial / immunology
  • Antibodies, Viral / immunology
  • Autoantibodies / immunology
  • Autoimmunity*
  • Bacterial Infections / complications*
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology
  • Bacterial Infections / microbiology
  • Complement System Proteins / immunology
  • Genetic Predisposition to Disease
  • Glomerulonephritis / etiology*
  • Glomerulonephritis / genetics
  • Glomerulonephritis / immunology
  • Glomerulonephritis / microbiology
  • Glomerulonephritis / virology
  • Host-Pathogen Interactions
  • Humans
  • Kidney* / immunology
  • Kidney* / microbiology
  • Kidney* / virology
  • Microbiota*
  • Risk Factors
  • Virus Diseases / complications*
  • Virus Diseases / genetics
  • Virus Diseases / immunology
  • Virus Diseases / virology


  • Antibodies, Bacterial
  • Antibodies, Viral
  • Autoantibodies
  • Complement System Proteins