I just sat through a terrific lecture here at the South African Renal Meetings by Sanjeev Sethi on membranoproliferative GN (MPGN). Recall we've seen nearly a dozen outstanding papers and a fantastic review in the NEJM by Sanjeev and his collaborator Fernando Fervenza, both at the Mayo clinic.
The gist of what Sanjeev was saying was this: the time has come for us to re-consider how we classify acute glomerulonephritis. Sanjeev and Fernando are suggesting that we adopt an etiologic classification – GN caused by one of 3 broad set of causes: antibody mediated, complement mediated, and cell-mediated. The resulting pattern of injury could be variable and depends on when in the course of disease the biopsy is performed. For example, an immune complex mediated process could present on biopsy early in the course as an acute proliferative GN with crescents but later in it’s course as a more indolent membranoproliferative GN.
The pattern of injury, Sethi argues, should not determining. Rather the focus should be on the etiologic mechanism. Accepting this concept then allows a different and more targeted approach toward treatment. It might spare some patients toxic therapy while others might receive treatment early. For example, a genetically mediated disorder of complement dysregulation such as a mutation in the factor H gene might cause C3 glomerulopathy. The treatment could include steroids but strategies targeted toward suppressing antibody production such as rituximab are unlikely to work.
I think Sanjeev and Fernando Fervenza at the Mayo clinic are on the right path. Tailoring immunotherapy therapy is the next frontier.