Acetaminophen: Acute and chronic effects on renal function

Acetaminophen (APAP) is normally metabolized in the liver and kidney by P450 enzymes, No toxicity is observed with therapeutic doses of APAP, However, after ingestion of large quantities of APAP (>2,000 mg/kg), highly reactive quinones, metabolites of APAP, are generated; these react with glutathione and sulfhydryl groups on critical proteins, resulting in cellular dysfunction and hepatic and renal toxicity, The P450 metabolizing enzymes differ somewhat in character between the liver and kidney, Factors that enhance renal toxicity include chronic liver disease, possibly gender, concurrent renal insults, and conditions that alter the activity of P450-metabolizing enzyme systems, Acute renal toxicity is characterized by cellular injury primarily confined to the proximal tubule and significant reductions in glomerular filtration rate, However, there is little evidence that chronic administration of APAP contributes to chronic renal disease and analgesic nephropathy, The only report on this subject suggests that combination therapy with aspirin is required for medullary damage in rats, No evidence exists for the development of chronic analgesic nephropathy with APAP alone, Epidemiologic studies in healthy individuals have failed to demonstrate a significant correlation between APAP use and chronic renal disease and classic analgesic nephropathy. Therefore, large doses of APAP can produce both renal and hepatic failure, but little evidence exists for production of classic analgesic nephropathy with the use of APAP alone. (C) 1996 by the National Kidney Foundation, Inc.