ANALGESIC NEPHROPATHY IN RODENTS

While it is clear that humans suffer from ''classic'' analgesic nephro pathy, the causative agents and mechanisms are still not known. A revi ew of the literature revealed that chronic acetaminophen exposure does not produce renal papillary necrosis in rodents or humans. In contras t, while chronic aspirin exposure to rodents results in renal papillar y necrosis with renal morphological and functional changes similar to that described in humans, epidemiological studies do not implicate asp irin alone in human analgesic nephropathy. The difference in the effec ts of aspirin in humans and rats may be due to the inability of epidem iological studies to detect aspirin-induced analgesic nephropathy or m ore likely to the fact that species differences exist, with the rat be ing more sensitive than humans. With respect to combinations of aspiri n and acetaminophen, with or without caffeine, there are minimal light ly controlled studies. In addition, there is little evidence of enhanc ed renal papillary necrosis in rodents treated with aspirin and acetam inophen combinations. In summary, it remains to be determined what che mical entities cause ''classic'' analgesic nephropathy in humans and t he 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.