ORIGINAL ARTICLE Kinin B1 receptor deficiency attenuates cisplatin-induced acute kidney injury by modulating immune cell migration Gabriel R. Estrela & Frederick Wasinski & Danilo C. Almeida & Mariane T. Amano & Angela Castoldi & Carolina C. Dias & Denise M. A. C. Malheiros & Sandro S. Almeida & Edgar J. Paredes-Gamero & João B. Pesquero & Carlos C. Barros & Niels O. S. Câmara & Ronaldo C. Araújo Received: 10 June 2013 /Revised: 29 November 2013 /Accepted: 2 December 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract Cisplatin is a chemotherapeutic agent that causes severe renal dysfunction. The kinin B1 receptor has been associated with the migration of immune cells to injured tissue as well as with renal inflammation. To examine the role of the kinin B1 receptor in cisplatin-induced acute kidney injury, we used kinin B1 recep- tor knockout mice and treatment with a receptor antagonist before and after cisplatin administration. Cisplatin injection caused exacerbation of renal macrophage and neutrophil mi- gration, higher levels of serum creatinine and blood urea, upregulation of B1 receptor mRNA and an increase in pro- inflammatory cytokines expression. B1 receptor knockout mice exhibited a reduction in serum creatinine and blood urea levels, diminished apoptosis, and decreased cisplatin-induced upregu- lation of inflammatory components. Moreover, treatment with the B1 receptor antagonist prior to cisplatin administration normalized serum creatinine, blood urea levels, protected from acute tubular necrosis, apoptosis-related genes, and prevented upregulation of pro-inflammatory cytokines. Thus, we propose that kinins have an important role in cisplatin-induced acute kidney injury by impairing immune cells migration to renal tissue during cisplatin nephrotoxicity. Key message & Kinin B1 receptor is upregulated after cisplatin exposure. & Kinin B1 receptor deficiency diminishes the nephrotoxi- city caused by cisplatin. & Kinin B1 receptor deficiency ameliorates the inflammato- ry response. & Kinin B1 receptor deficiency diminishes apoptosis caused by cisplatin. & Kinin B1 receptor antagonism ameliorates renal function after cisplatin injection. Keywords Kinins . Nephrotoxicity . Cisplatin . Acute kidney injury . Inflammation Introduction Cisplatin is an antitumor agent frequently used in chemother- apy; however, nephrotoxicity is recurrently associated with cisplatin treatment and is a limiting factor for its use. Renal injury is the result of the apoptosis and/or necrosis of renal Electronic supplementary material The online version of this article (doi:10.1007/s00109-013-1116-z) contains supplementary material, which is available to authorized users. G. R. Estrela : F. Wasinski : C. C. Dias : S. S. Almeida : E. J. Paredes-Gamero : J. B. Pesquero : R. C. Araújo Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, Brazil G. R. Estrela : F. Wasinski : D. C. Almeida Departamento de Medicina, Disciplina de Nefrologia, Universidade Federal de São Paulo, São Paulo, Brazil M. T. Amano : A. Castoldi : N. O. S. Câmara Instituto de Ciências Biomédicas, Departamento de Imunologia, Universidade de São Paulo, São Paulo, Brazil D. M. A. C. Malheiros Departamento de Clinica Médica, Universidade de São Paulo, São Paulo, Brazil C. C. Barros Departamento de Nutrição, Escola de Nutrição, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil R. C. Araújo (*) Department of Biophysics, Federal University of São Paulo, Rua Botucatu, 862, 7° andar, 04023-062 São Paulo, São Paulo, Brazil e-mail: araujo.ronaldo@unifesp.br J Mol Med DOI 10.1007/s00109-013-1116-z