Toxic properties of the mushroom Cortinarius orellanus (Fries). II. Impairment of renal function in rats.

Oral administration of the toxic mushroom Cortinarius orellanus (Fr.) to male Sprague Dawley rats caused serious impairment of renal function. The signs observed were similar to those produced in humans who ingest this fungus. Administration of 2.0 g dried Cortinarius orellanus per kg body weight led to acute renal dysfunction within 48 h. The pattern of impairment included reduced glomerular filtration rate, decreased renal absorption of water, sodium and potassium, and proteinuria and glucosuria. The nephrotoxic effect was further characterized by decreased activities of the brush border enzymes alkaline phosphatase and gamma-glutamyltranspeptidase in urine, despite a remarkable increase in protein excretion of predominantly tubular origin. These findings were substantiated by morphologic changes, which could be detected as early as 12 h after dosing. Morphologically discernible signs of renal tubular damage start with deformation of the proximal tubular brush border region. Within 48 h after toxin ingestion, prenecrotic and necrotic cells could be found in all nephron segments contained in the renal cortex. The most prominent changes were a vesiculation of the apical cell pole and a swelling of the smooth surfaced endoplasmic reticulum and of mitochondria. The latter was accompanied by a loss in matrix material and a massive fragmentation of mitochondrial cristae membranes. Detectable quantities of the toxic principle of the mushroom, orellanine, were excreted only within the first 24 h after dosing. No impairment of liver function was detected.