Renal microcirculatory perfusion in a pediatric model of sepsis‐induced acute kidney injury in the rat

Abstract

Sepsis is a leading cause of acute kidney injury (AKI) and mortality in children. Understanding the development of pediatric sepsis and its effects on the kidney are critical to finding new therapies. The goal of this study was to characterize the development of sepsis-induced AKI in a clinically relevant cecal ligation and puncture (CLP) model of peritonitis in 17–18 day old rat pups. CLP produced severe sepsis demonstrated by a time-dependent increase in serum cytokines, NO, markers of multi-organ injury including creatinine, and renal microcirculatory hypoperfusion. Although blood pressure and heart rate remained unchanged after CLP, renal blood flow (RBF) was decreased. Renal microcirculatory analysis showed the number of continuously flowing cortical capillaries decreased along with red blood cell velocity and volumetric flow. This was also accompanied by induction ICAM-1 and inducible nitric oxide synthase in the kidney with subsequent peroxynitrite generation. In contrast to sham pups, sham adults had higher blood pressure, RBF, and microcirculatory perfusion. With the exception of blood pressure, CLP produced a greater decrease in these hemodynamic parameters in pups compared to adults, suggesting that the pediatric kidney may be more susceptible to not only sepsis-induced AKI, but also to other forms of AKI due to its relatively low blood flow and microcirculatory perfusion. Supported by DK075991.