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Modulation of the renal inflammatory process by the inhibition of B1 receptors of kinins in immunological cells

Grant number: 18/05880-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2018
Effective date (End): October 31, 2020
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Ronaldo de Carvalho Araújo
Grantee:Leonan Spagnolo Benites
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:15/20082-7 - Kallikrein kinin system in physical exercise and metabolism, AP.TEM

Abstract

Evidence indicates that the incidence of acute kidney injury (AKI) is increasing rapidly, particularly among patients hospitalized with other acute diseases and those undergoing major surgeries. The sequelae are severe and are characterized by an increased risk of short- and long-term mortality. Although mortality associated with AKI is declining, it remains unacceptably high. This decrease hides the fact that the absolute number of patients evolving to death is increasing, while there are still few effective preventive or therapeutic interventions proven. LRA survivors, particularly those who remain on renal replacement therapy, present a significant reduction in quality of life and consume substantially greater health care resources when compared to the general population as a result of longer hospitalizations and unplanned hospitalizations in ICUs. This renal injury occurs due to the exacerbated migration of neutrophils and macrophages to the kidney in an attempt to combat some non-physiological situation, causing the release of a series of substances that, in excess, lead to irreversible renal tissue damage. Some drug treatments have the side effect of compromising the renal cells, allowing the appearance of an acute inflammation. For example, cisplatin, which is used in an experimental model, allows the induction of a renal inflammatory process, leading to AKI. In this process, the kinin-kallikrein system acts as the signaling role for recruitment and mobilization of macrophages and neutrophils to the injured site, using B1 receptors expressed in these cells. If it's demonstrated that the inhibition of B1R receptors in immunological cells directly influences the reduction of the renal inflammatory process, space is created for studies, focused on the development of medications with inhibitory actions specifically in these receptors. That can be offered as a complement to patients who needs treatments with drugs that lead to renal lesions, attenuating this side effect and promoting a better response to the various treatments that may be necessary, including the cisplatin used in the study.