Summary Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of obstructive nephropathy in children. Neonatal and foetal animal models have been developed that mimic closely what is observed in human disease. The purpose of this review is to discuss how obstructive nephropathy alters kidney histology and function and describe the molecular mechanisms involved in the progression of the lesions, including inflammation, proliferation/apoptosis, renin–angiotensin system activation and fibrosis, based on both human and animal data. Also we propose that during obstructive nephropathy, hydrodynamic modifications are early inducers of the tubular lesions, which are potentially at the origin of the pathology. Finally, an important observation in animal models is that relief of obstruction during kidney development has important effects on renal function later in adult life. A major short‐coming is the absence of data on the impact of UPJ obstruction on long‐term adult renal function to elucidate whether these animal data are also valid in humans.

Renal fibrosis is the common histological feature of advanced glomerular and tubulointersti‐tial disease leading to end‐stage renal disease (ESRD). However' specific antifibrotic therapies to slow down the evolution to ESRD are still absent. Because persis‐tent inflammation is a key event in the development of fibrosis' we hypothesized that the proinflammatory kinin B1 receptor (B1R) could be such a new target. Here we show that' in the unilateral ureteral obstruction model of renal fibrosis' the B1R is overexpressed and that delayed treatment with an orally active non‐peptide B1R antagonist blocks macrophage infiltration' leading to a reversal of the level of renal fibrosis. In vivo bone marrow transplantation studies as well as in vitro studies on renal cells show that part of this antifibrotic mechanism of B1R blockade involves a direct effect on resident renal cells by inhibiting chemokine CCL2 and CCL7 expression. These findings suggest that blocking the B1R is a promising antifibrotic therapy.—Klein, J., Gonzalez, J., Duchene, J., Esposito, L., Pradere, J. P., Neau, E., Delage, C., Calise, D., Ahluwalia, A., Carayon, P., Pesquero, J. B., Bader, M., Schanstra, J. P., Bas‐cands, J. L. Delayed blockade of the kinin B1 receptor reduces renal inflammation and fibrosis in obstructive nephropathy. FASEBJ. 23′ 134‐142 (2009)

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