Models of Glycerol-Induced Acute Renal Failure in Rats

Abstract

Acute renal failure (ARF) following rhabdomyolysis is not uncommon in man. The popular model for ARF formation following rhabdomyolysis in experimental animals is glycerol injection into the leg muscle following a 24 hour period of water deprivation. A large percentage of patients developing ARF following rhabdomyolysis do not suffer from such long periods of water deprivation. On the contrary, fluid loss in patients developing ARF is relatively fast and is the result of excessive sweating or hemorrhage. Since it is known that the hydration state of the body during rhabdomyolysis considerably affects the development of ARF, it seems that the popular model of glycerol injection following a prolonged period of water deprivation in experimental animals is, to a certain extent, deficient. The aim of the present study was to examine two models of ARF formation in the rat following glycerol injection and acute diminution of the body's water content: 1) by sucrose injection (200 mg/100 g), 2) by hemorrhage (0.7 ml/100 g). A number of differences were found between the various models of ARF formation by glycerol. The differences are mainly expressed in the urine volume three hours after the glycerol injection. In the sucrose and hemorrhage groups a decrease of 29% and 66% (p < 0.001) in urine volume was found at the end of the experiment. In contradistinction, in the group that underwent water deprivation for a period of 24 hours prior to the glycerol injection, an increase of 46% (p < 0.001) in the urine volume was observed at the end of the experiment. Differences were also found in potassium uptake and in the extent of the decrease in renal cortex blood flow as measured by the laser Doppler flowmetry technique. From this study it may be concluded that glycerol injection to the rat leg muscle results in ARF in all three methods of decreasing the body's fluid content. It is possible that the models of sucrose injection or hemorrhage prior to glycerol injection are better suited for reflecting the hydration condition of humans suffering from rhabdomyolysis than 24 hours of water deprivation prior to this injection.