Anti-complement therapy for glomerular diseases

A major shift in our understanding of glomerular diseases is the focus on which components of the complement pathway are involved in mediating kidney injury. For example, the membranoproliferative glomerulonephritis lesion is no longer classified solely by ultrastructural findings on biopsy and is now divided into immune-complex-mediated lesions vs complement-mediated lesions. In turn, this emphasis on complement leads to interest in therapies that target complement as potential disease-modifying agents. Eculizumab, the first available anti-complement therapy, blocks at the level of C5 and has revolutionized the treatment of atypical hemolytic uremic syndrome. Whether this agent will work equally well for the far more heterogeneous entities of C3 glomerulonephritis and dense deposit disease remains unclear. Instead, newer agents that target C3 may turn out to be the most effective and specific therapy for these C3 glomerulopathies.