Analgesic nephropathy in rodents.
While it is clear that humans suffer from "classic" analgesic nephropathy, the causative agents and mechanisms are still not known. A review of the literature revealed that chronic acetaminophen exposure does not produce renal papillary necrosis in rodents or humans. In contrast, while chronic aspirin exposure to rodents results in renal papillary necrosis with renal morphological and functional changes similar to that described in humans, epidemiological studies do not implicate aspirin alone in human analgesic nephropathy. The difference in the effects of aspirin in humans and rats may be due to the inability of epidemiological studies to detect aspirin-induced analgesic nephropathy or more likely to the fact that species differences exist, with the rat being more sensitive than humans. With respect to combinations of aspirin and acetaminophen, with or without caffeine, there are minimal tightly controlled studies. In addition, there is little evidence of enhanced renal papillary necrosis in rodents treated with aspirin and acetaminophen combinations. In summary, it remains to be determined what chemical entities cause "classic" analgesic nephropathy in humans and the mechanisms of this toxicity such that preventative measures can be instituted. Elucidation of the mechanisms of analgesic nephropathy has been hampered due to the lack of animal models that closely mimic the human disease. Rodents do not appear to be an appropriate model.
Schnellmann
R G
RG
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA. rschnell@biomed.uams.edu
D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D002110:Caffeine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007681:Kidney Papillary Necrosis / Q000139:chemically induced*; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced; D010615:Phenacetin / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D002110:Caffeine; D010615:Phenacetin; D001241:Aspirin