Even delayed targeting of reactive oxygen species/oxidative stress protects the renal microcirculation during sepsis‐induced renal injury in mice

Sepsis‐induced acute kidney injury (SAKI) is a frequent complication in septic patients. Understanding the pathogenesis of SAKI is important because most therapy is begun only after patients become septic. We tested the hypothesis that renal injury is dependent on reactive oxygen species (ROS) generation and that targeting ROS may protect the kidney. The cecal ligation and puncture (CLP) model of sepsis was used in male 40 wk C57BL/6 mice. Intravital video microscopy was used to measure peritubular capillary perfusion, redox stress, and superoxide generation (MitoSox fluorescence) in the peritubular capillary microenvironment. As early as 4h post CLP there was decreased renal blood flow and capillary perfusion, tubular hypoxia, and increased tubular superoxide generation. To examine the role of ROS, animals were treated with the SOD mimetic MnTMPyP (10 mg/kg ip) at 6h post CLP. MnTMPyP significantly reduced ROS, restored peritubular capillary perfusion, decreased subsequent tubular redox stress and BUN levels at 18h post CLP (n=4–7; each parameter p<.05 vs Sham). These data support the hypothesis that ROS generation plays an important role in the development of SAKI. Importantly, even delayed treatment with MnTMPyP was protective and agents that are protective even after the onset of sepsis could have the greatest impact on patient outcomes. Supported by AHA 10PRE4140065 (ZW) and NIH DK075991 (PRM).