54

Necrotizing and crescentic rapidly progressive glomerulonephritis or crescentic glomerulonephritis is one of the severest forms of acquired glomerular diseases with significant mortality. Risk of end-stage renal failure at 5 years is near 30%, with a number of patients developing chronic kidney disease. Currently, autoimmune crescentic glomerulonephritides are treated with broad-spectrum immunosup- pression inducing remission of the injury in the majority of patients. However, treatment is associated with significant side effects and by the time remission is achieved the majority of patients have developed renal tissue damage and significant impairment of their kidney function with a steep slope of deterioration within the first weeks following initiation of immunosuppression. It is therefore important to develop complementary strategies that would be immediately active on the common process of destructive epithelial processes. We have worked to identify the major cellular pathways contributing to glomerular destruction in this context by a systematic comparison of patient tissues and experimental models. Our studies demonstrate the pivotal role of local intra- and intercellular communications in orchestrating the global glomerular tolerance to a severe rapidly progressive glomerulonephritis model with excellent anatomoclinical correlative expressions in kidney biopsies of individuals diagnosed with crescentic glomerulonephritis, irrespectively of the causal immune disorder. We hope that such approaches deciphering mechanisms of cellular adaptation that underlie kidney damage control in response to vasculitides, integrating both stress and damage responses, will delineate novel complementary therapies.© 2019 Socie´ te´ francophone de ne´ phrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.