Experimental paracetamol nephropathy and pyelonephritis in rats

The nephrotoxicity of paracetamol (acetaminophen) administered to rats in doses of 300 mg/kg/day for periods up to 32 weeks was increased in the presence of experimentally induced pyelonephritis. The same dose of paracetamol failed to cause renal lesions in rats without pyelonephritis. Generally the pyelonephritic reactions were more severe in animals receiving paracetamol as compared to those in whom the drug was witheld. Thickened basement membranes of microvessels and tubules associated with papillary necrosis, and attempted healing of a necrotic papillary stump were unusual experimental findings which resemble pathology considered characteristic of clinical analgesic nephropathy.