Ameliorative effects of bevacizumab against sepsis-induced acute kidney injury: investigation of inflammatory responses, pyroptosis-related signalling and angiogenesis in a murine model of polymicrobial sepsis

Background: Sepsis is a clinical issue with a major impact on in-hospital patients, resulting in multiple organ damage and increased risk of death. Acute kidney injury (AKI) is the most common organ that is vulnerable to sepsis and may progress to renal failure if not treated. Bevacizumab is a biopharmaceutical agent that disrupts the angiogenesis signalling pathway by binding to vascular endothelial growth factor (VEGF) and preventing it from coupling with cognate receptors. The present study aimed to assess the renoprotective potential of bevacizumab against sepsis-induced renal injury.

Methods and results: Four cohorts (6 mice per group) were randomly allocated and included a sham cohort, which was exposed to a midline incision only; the cecal ligation and puncture (CLP) cohort underwent CLP; the vehicle cohort was pretreated with normal saline 1 h prior to the CLP; and the bevacizumab cohort was treated with 0.1 mg/kg bevacizumab 1 h before the CLP. After 24 h, the mice were euthanised, and the blood and kidneys were collected. The results revealed that the levels of urea, creatinine, TNF-α, IL-6, Caspase 11, ICAM-1, VEGF and angiopoietin-2 were greater in septic mice than in sham mice. These levels were decreased in septic mice pretreated with bevacizumab. Histological assessment of renal tissues revealed that the kidneys of septic mice were injured, influencing 90% of the renal tubules. Pretreatment with bevacizumab mitigated renal tissue damage.

Conclusion: This study demonstrated that bevacizumab has promising renoprotective effects against sepsis-induced renal injury via modulation of inflammatory responses, angiogenesis and pyroptosis-associated signalling.