Effective renal blood flow and renal energy charge in murine peritonitis

The temporal sequence of physiological derangements preceding acute renal failure (ARF) observed in overwhelming bacterial septicemia remains controversial. In order to examine the relationship of renal circulatory alterations and cellular dysfunction in murine sepsis, effective renal plasma flow (ERPF), renal tissue metabolites, and energy charge ratios were determined in Sprague-Dawley rats at 10 and 20 hours following induction of peritonitis by cecal ligation and perforation (CLP) or cecal manipulation alone (sham). Tissue levels of adenine nucleotides, lactate, and pyruvate were assayed after freeze-clamping kidneys unilaterally followed by enzymatic determinations. Cardiac outputs were determined by thermodilution and ERPF by p-aminohippuric acid (PAH) clearance. Results indicate in this model, despite an increase in cardiac output (P less than 0.05), ERPF was significantly decreased at both 10 hours (P less than; 0.05) and 20 hours (P less than 0.01) following induction of peritonitis. Further, although tissue pyruvate/lactate ratios showed significant decreases by 10 hours (P less than 0.05), diminished energy charge ratios were not observed until 20 hours following septic insult. These findings support the hypothesis of diminished renal perfusion as contributory and antecedent to cellular dysfunction in septicemic ARF.