Acute renal failure and tubular damage due to sepsis in an animal model

Generalised sepsis was induced in sheep by caecal perforation. Serial measurement of haemodynamic parameters revealed that the subsequent generalised sepsis induced increased cardiac output and decreased systemic resistance comparable to that known to occur in man. Glomerular filtration rate in these animals fell significantly 48 hours after induction of sepsis and there was evidence of tubular damage in the finding of low molecular weight proteinuria and increased clearance of lysozyme. Pathological examination of the kidney revealed normal glomeruli, no consistent changes in tubular cells on light microscopy, negative immunofluorescence, but structural changes in proximal tubular cells on EM. In this model, non-hypotensive sepsis predictably produces damage to proximal tubular cells accompanied by reduction in GFR.