Glomerulonephritis: immunopathogenesis and immunotherapy

‘Glomerulonephritis’ (GN) is a term used to describe a group of heterogeneous immune-mediated disorders characterized by inflammation of the filtration units of the kidney (the glomeruli). These disorders are currently classified largely on the basis of histopathological lesion patterns, but these patterns do not align well with their diverse pathological mechanisms and hence do not inform optimal therapy. Instead, we propose grouping GN disorders into five categories according to their immunopathogenesis: infection-related GN, autoimmune GN, alloimmune GN, autoinflammatory GN and monoclonal gammopathy-related GN. This categorization can inform the appropriate treatment; for example, infection control for infection-related GN, suppression of adaptive immunity for autoimmune GN and alloimmune GN, inhibition of single cytokines or complement factors for autoinflammatory GN arising from inborn errors in innate immunity, and plasma cell clone-directed or B cell clone-directed therapy for monoclonal gammopathies. Here we present the immunopathogenesis of GN and immunotherapies in use and in development and discuss how an immunopathogenesis-based GN classification can focus research, and improve patient management and teaching. The authors propose a new grouping of glomerulonephritis disorders based on their underlying immunopathogenesis, with a view to improving diagnosis, mechanistic understanding and treatment of these immune-mediated kidney diseases.