Early nephrotoxicity at high plasma concentrations of lysozyme in the rat

In clearance experiments, egg white lysozyme was intravenously infused into male Wistar and Wistar/Furth rats over different periods of time to achieve plasma concentrations of lysozyme in the range of 30 to 8000 micrograms per ml. The glomerular filtration rate and the appearance of glomerular and tubular epithelia were comparable to those of control rats below 3000 micrograms per ml. of plasma concentration of lysozyme and up to 60 minutes' infusion time when investigated by scanning electron microscopy. A 50 per cent drop in blood pressure occurred at a plasma lysozyme concentration of 3000 micrograms per ml., which could be prevented by the intravenous injection of an antihistamine or by using Wistar/Furth rats; however, the decrease of the glomerular filtration rate and of the fractional lysozyme reabsorption as well as the increase in sodium and potassium excretion could not be avoided. After 30 minutes of lysozyme infusion, the epithelial foot processes exhibited slight regional effacement, and in more than 50 per cent of the tubules protein cast formation was noted. Occurrence of foot process effacement and tubular casts increased with further increase of plasma lysozyme concentration and lysozyme infusion time. These morphologic changes were common for Wistar rats, antihistamine-pretreated Wistar rats, Wistar/Furth rats, and in situ-perfused rat kidneys. These results indicate that the cationic low molecular weight protein lysozyme induced functional and structural alterations that were correlated with plasma lysozyme concentration and lysozyme infusion time and caused acute renal failure.