Metabolic studies of glycerol-induced acute renal failure in the rat

Abstract

Glycerol was used to induce acute renal failure (ARF) in rats. It caused a decrease of kidney ATP levels to 48% of control at 6 hr which remained low up to 48 hr. ATP + ADP + AMP(AXP) was 55% of control at 6 and 24 hr and 64% at 48 hr. Lactate levels were fourfold control levels at 0.25, 1, and 6 hr, and twofold at 24 and 48 hr. Hemoglobinemia and hemoglobinuria occurred within 0.25 hr. By light microscopy, casts at 6 hr, necrosis of renal cortex at 24 hr, and necrosis with some regeneration at 48 hr were seen. Fructose at the same dose also lowered ATP and AXP levels to a similar degree as glycerol within the same time intervals, but hemoglobinemia, hemoglobinuria, necrosis, or ARF was not evident. Dihydroxycetone at the same dose maintained ATP and AXP at control values with no hemoglobinemia, hemoglobinuria, necrosis, or ARF. Both fructose and dihydroxyacetone resulted in high lactate levels (sevenfold) within 0.25 hr. Saline loading prior to glycerol infection ameliorated ARF but did not improve the AXP levels or the morphologic lesion. Results indicate that glycerol-induced ARF is not solely the result of a hyperosmolar effect, adenosine release, casts, or pigments. The changes in AXP (particularly ATP) levels reflect an early metabolic disturbance which is part of the process and may predispose toward ARF in the presence of additional factors.