Role of endotoxin in glycerol-induced renal failure in the rat.

1. A relationship between bacterial endotoxin absorbed from the gut and acute renal failure has been postulated. Experiments employing either the endotoxin-tolerant state or the enhancement of endotoxin injury were undertaken to test this relationship in rats. 2. Endotoxin tolerance was induced by the administration of increasing doses of Escherichia coli 026 lipopolysaccharide. The severity of renal injury was assessed at various times after glycerol administration in endotoxin-tolerant and control animals. At 48 h, endotoxin-tolerant rats had higher urine volume and creatinine clearance than the non-tolerant control animals. In rats studied 72 h after glycerol, functional and anatomical assess­ ment showed the endotoxin-tolerant rats to have lower serum urea concentrations and also less renal histological injury than the non-tolerant, control animals. 3. Lead acetate, which potentiates endotoxin injury, or diluent alone was administered to rats after glycerol. At 2, 3 and 10 days later there was a twofold increase in mortality in the lead acetatetreated animals. 4. A small dose of endotoxin (0-1 mg) was shown to be innocuous in control rats. Also, all rats given glycerol alone were alive 24 h later. In contrast, administration of the same dose of endo­ toxin simultaneously with glycerol resulted in an 80% mortality at 24 h.