Analgesics and Kidney Disease

The National Institutes of Health (NIH) recently issued a report stating that 'combinations of antipyretic analgesics, taken in large doses over a prolonged period, cause a specific form of kidney disease and chronic renal failure.' This hypothesis has been widely held for many years. The NIH report may faithfully describe the consensus in medicine today, but it is not informative about what is known concerning analgesics and kidney disease. Our purpose here is to provide criticism of some popular ideas presented in the NIH report, and at the same time suggest ways to further our understanding of the possible role of analgesics in the development of kidney disease. The concerned analgesic-user, clinician or policymaker will note that the hypothesis in its present form is too imprecise to be useful. The primary questions of interest should be: what types and quantities of analgesics, if any, cause kidney disease? The current hypothesis indicts combination analgesics without specifying which types of analgesics are thought to be involved. All types of analgesics are implicitly alleged to be hazardous, but the evidence differs considerably for individual analgesics. An increased rate of papillary necrosis has been observed among female phenacetin users, most of whom ingested a cumulative dose of more than 2 kg. There is little evidence indicating that analgesics not containing phenacetin are associated with kidney disease in humans.Interactive effects of combinations of analgesics as compared to single ingredient preparations have not been studied. In claiming a causal relation for combination analgesics 'taken in large doses over prolonged periods' but not for single ingredient analgesics 'when taken in the smaller doses usually prescribed by physicians,' analgesic type is confounded with dose. The vague nature of the theory reflects severe limita-