Renal microcirculatory dysfunction in sepsis‐induced acute kidney injury (AKI) in mice

Abstract

Understanding the sequence of events leading to sepsis‐induced renal injury, especially at the early stages of sepsis, is critical for developing new therapy to reduce mortality that is currently greater than 50%. The cecal ligation and puncture (CLP) model of sepsis was used to study the development of AKI in male 40‐week C57BL/6 mice. Intravital video microscopy (IVVM) was used to monitor and quantitate changes in the peritubular microenvironment in sham surgery mice and at 2, 4, or 6 h following CLP. IVVM revealed a dramatic fall in peritubular capillary perfusion as early as 2 h post CLP. The percentages of cortical peritubular capillaries with continuous flow dropped from 85 ± 4% to 66 ± 6% (P < .05, n = 6) and continued to worsen through 6 h. We also observed that cellular levels of NAD(P)H, an indicator of cellular redox stress measured by IVVM, were elevated following CLP but lagged behind the fall in capillary perfusion. These data show that a compromised renal cortical microcirculation is a very early event in the development of sepsis. The data also indicate a critical relationship between peritubular capillary dysfunction and the development of tubular stress and renal injury during sepsis. This study suggests that therapeutic approaches targeting the peritubular capillary that improve the renal microcirculation could reduce sepsis‐induced AKI. Supported by AHA Grant In Aid #850227Z.