Renal insufficiency induced by locally administered endotoxin in rabbits

Renal failure in sepsis often occurs without other organ failure such as cardiovascular or pulmonary dysfunction. An endotoxin-induced renal insufficiency model using rabbits, which does not complicate other organ failure, was developed. To selectively damage kidneys endotoxin (40 micrograms/kg/h, 3 h) was infused through a cannula placed into the abdominal aorta just distally to the take-off of the superior mesenteric artery after ligation of the aorta below the junction of renal arteries. The following manifestations of renal insufficiencies were observed with high reproducibility: oliguria, increase in plasma creatinine (from 1.1 to 1.6 mg/dl) and urine N-acetyl-beta-D-glucosaminidase (from 7.9 to 23.7 U/l), decrease in effective renal plasma flow (33%) and glomerular filtration rate (35%), and an apparent renal ischemic change in the histological examination. On the other hand, blood pressure, heart rate, respiration rate, body temperature and hematocrit were not significantly altered. The present model is useful for studying the effects of drugs on renal insufficiency in sepsis or endotoxemia and its pathogenesis. Most renal insufficiencies in clinical sepsis may be caused by endotoxin-induced renal ischemic change due to neither low blood pressure nor renal microthrombi.