Influence of fluid resuscitation on renal function in bacteremic and endotoxemic rats

Abstract

Purpose: Fluid resuscitation, which is the most important primary therapy in sepsis, is not always able to prevent acute renal failure. In this study, we investigated in two different rat models of distributive shock whether fluid resuscitation would increase renal plasma flow (RPF) and subsequently glomerular filtration rate (GFR). Materials and Methods: In pentobarbital anesthetized Wistar rats Haemaccel (Behring Pharma, Hoechst, the Netherlands) infusion (1.2 mL/100 g/h for 3 hours) was started immediately during either bacteremia (bolus of living Escherichia coli bacteria, 109 or endotoxemia (1 hour infusion of E. coli endotoxin, 8 mg/kg), as well as in time-matched healthy controls. Results: After 3 hours, this treatment had increased RPF (clearance of 1311-hippurate) above normal in control (+67%) and bacteremic rats (+75%), whereas in endotoxemic animals, the significantly decreased RPF was normalized. On the other hand, in bacteremic animals, the lowered GFR (clearance of creatinine; ×44%) was normalized, whereas in endotoxemic animals GFR remained depressed (×30%). The lack of improvement in GFR during endotoxemia was also indicated by a profound fall in urine flow, which by contrast steadily increased in control and bacteremic rats owing to volume loading. In both shocked groups, the decreased renal oxygen delivery was normalized, but the higher renal oxygen consumption than expected on the basis of the work needed for sodium reabsorption was not influenced by Haemaccel treatment, despite the fact that it caused this work load to rise in bacteremic but not in endotoxemic rats. In both shock models, renal cortical adenosine triphosphate content did not differ from healthy controls and was not influenced by volume loading. Conclusions: In conclusion, our study suggests that a decrease in GFR caused by live bacteria in the circulation may benefit from fluid resuscitation, while during endotoxemia this therapy could not prevent acute renal failure.