FP230
VEGFR2 KINASE INHIBITION AGGRAVATES FOLIC ACID INDUCED ACUTE RENAL DAMAGE

INTRODUCTION AND AIMS: Acute kidney injury (AKI) is a multifactorial pathology without known effective treatment. Some strategies have been recently suggested in order to control inflammation or cell death and thought as a potentially therapeutic option. Our group has recently demonstrated that VEGFR2 blockade diminishes experimental renal damage in unilateral ureteral obstruction model and Gremlin-induced damage, because it inhibits the inflammatory response, but there is no data available in experimental AKI models.

METHODS: AKI was conducted in C57BL/6 mice strain by a daily intraperitoneal injection of folic acid [250mg/kg]. Starting 24h before of folic acid injection, some mice were injected every day with the VEGFR2 kinase inhibitor SU5416 [10mg/kg]. Mice were sacrificed two days after administration of folic acid in order to analyse the results.

RESULTS: Histological renal damage was evaluated by PAS tinction and it showed an increase in acute tubular damage and inflammatory infiltrate in AKI treated with SU5416 mice when compared with non-treated AKI mice and healthy controls (the latter did not present renal injury). Due to this, it was decided to analyse the renal damage markers KIM-1 and NGAL, which gene expression levels was highly increase in both genes in SU5416-treated AKI mice vs AKI and control mice. Gene expression levels of pro-inflammatory cytokines such as MCP-1 and Rantes were also studied. There were no significant differences between groups, but in MCP-1 a slightly increase was observed compared to not-treated ones. When analyzing myeloperoxidase, which is a marker of neutrophils, by immunohistochemistry it was observed a significant increase in SU5416 treated AKI mice when compared to non-treated mice. Nevertheless, no differences between these groups in CD3 lymphocytic marker were found.

CONCLUSIONS: The blockade of VEGFR2 pathway by SU5416 in AKI induces an increase renal damage. Therefore, the inhibition of this pathway is not a good therapeutic option for AKI, unlike what was observed in progressive renal damage models.