Romagnani, P.; Kitching, A. R.; Leung, N.; Anders, H.-J.
Glomerulonephritis (GN) is a diverse group of immune-mediated disorders. Currently, GN is classified largely by histological patterns that are difficult to understand and teach and most importantly, do not indicate treatment choices. Indeed, altered systemic immunity is the primary pathogenic process and the key therapeutic target in GN. Here, we apply a conceptual framework of immune-mediated disorders to GN guided by immunopathogenesis and hence immunophenotyping: 1) Infection-related GN require pathogen identification and control, 2) Autoimmunity-related GN, defined by presence of autoantibodies, and 3) Alloimmunity-related GN in transplant recipients both require the suppression of adaptive immunity in lymphoid organs and bone marrow, 4) Autoinflammation-related GN, e.g. inborn errors of immunity diagnosed by genetic testing, requires suppression of single cytokine or complement pathways, and 5) Monoclonal gammopathy-related GN requires B or plasma cell clone-directed therapy. A new GN classification should include a) disease category, b) immunological activity to tailor the use of the increasing number of immunomodulatory drugs, and c) chronicity to trigger standard CKD care including the evolving spectrum of cardio-renoprotective drugs. Certain biomarkers allow diagnosis and the assessment of immunological activity and disease chronicity without kidney biopsy. These five GN categories and a therapy-focused GN classification is likely to overcome some of the existing hurdles in GN research, management, and teaching by reflecting disease pathogenesis and guiding the therapeutic approach.