AbstractFocal and segmental glomerulosclerosis (FSGS) is one of the most important renal diseases related to end stage renal failure. Bradykinin has been implicated in the pathogenesis of renal inflammation whereas the role of its receptor 2 (B2RBK) in FSGS has not been studied. FSGS was induced in wild type and B2RBK KO mice by a single intravenous injection of Adriamycin (ADM). In order to further modulate the kinin receptors, animals were also treated with B2RBK antagonist HOE-140, and DALBK, B1RBK antagonist. Here, we show that the blockage of B2RBK with HOE-140 protects mice from FSGS development, including podocyte foot process effacement and reestablishment of slit diaphragm-related proteins. However, B2RBK KO mice were not protected from FSGS. These opposite results were due to B1RBK expression. B1RBK was up regulated after ADM injection and it was exacerbated in B2RBK KO animals. Further, HOE-140 treatment down regulated B1RBK receptor. The blockade of B1RBK in B2RBK KO animals promoted FSGS regression, with a less inflammatory phenotype. These results indicate a deleterious role of both kinin receptors in FSGS model and suggest a possible crosstalk of them in disease progression.