Pathogenic mechanisms in membranoproliferative glomerulonephritis.
OBJECTIVE
This review considers new information on the pathogenesis of a long recognized and poorly understood form of glomerular injury, membranoproliferative glomerulonephritis. This disease has received growing attention as it is the principal renal manifestation of hepatitis C virus infection, which has become pandemic worldwide.


RESULTS
This review briefly describes three murine models of membranoproliferative glomerulonephritis suitable for pathogenesis studies. We consider recent evidence implicating innate immune mechanisms in immune and autoimmune-mediated glomerulonephritis, and recent data pointing to the alternative pathway of complement activation in the amplification of glomerulonephritic injury.


CONCLUSIONS
Understanding the contribution of complement activation and innate immunity to the evolution of membranoproliferative glomerulonephritis promises to provide new therapeutic targets for this disease. Inhibitors of the complement cascade are already being tested in clinical trials as therapeutic interventions for some human glomerular diseases. Successful tests of this approach in membranoproliferative glomerulonephritis are still awaited. Our understanding of how the innate immune system modulates glomerulonephritis is still in an early stage, and future studies should be directed at identifying targets and specific interventions that may also benefit patients with this disease.
Smith
Kelly D
KD
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Alpers
Charles E
CE
D000818:Animals; D003165:Complement System Proteins / Q000276:immunology; D004195:Disease Models, Animal; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology* / Q000276:immunology / Q000821:virology; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology
D003165:Complement System Proteins