Renal hemodynamic, microcirculatory and metabolic responses to peritonitis-induced acute kidney injury in pigs

Introduction

The widely held paradigm that renal vasoconstriction may not be a prerequisite for septic acute kidney injury (AKI) has recently been challenged [1]. Further research is needed to establish whether this concept is valid in other clinically relevant models of sepsis-induced AKI [2]. The aim of our study was therefore to dynamically assess the pattern of renal hemodynamics, microcirculation and energy balance during a hyperdynamic porcine model of progressive septic shock.

Methods

In eight anesthetized, mechanically ventilated and instrumented pigs, fecal peritonitis was induced by inoculating autologous feces. Six sham-operated animals served as time-matched controls. Hyperdynamic circulation was achieved using hydroxyethylstarch, and norepinephrine was administered to maintain mean arterial pressure ≥ 70 mmHg. Before and at 12, 18 and 24 hours of peritonitis, we measured, in addition to systemic hemodynamics, renal blood flow, renal cortex microvascular perfusion, renal venous pressure, renal oxygen kinetics and regional acid–base balance and lactate/pyruvate (L/P) ratios.

Results

All pigs developed hyperdynamic septic shock associated with the development of AKI as evidenced by increased plasma creatinine levels to 30% of baseline. Although the renal blood flow slightly decreased by the end of the experiment, renal vascular resistance remained unchanged. Despite maintained regional hemodynamics, there was significant and early decline in renal cortex microvascular perfusion. Although renal oxygen consumption did not change, renal venous acidosis and an increased L/P ratio developed.

Conclusion

Septic AKI was not associated with renal vasoconstriction. While early alterations in renal cortex microcirculation preceded a minor decline in renal blood flow, unchanged renal oxygen consumption together with signs of significant metabolic stress suggests that the basis for septic AKI may be attributable not only to changes in microcirculatory perfusion, but also to disturbed cellular energy machinery independent of tissue oxygen availability.