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June 15, 1984

Analgesic-Associated Kidney Disease

JAMA. 1984;251(23):3123-3125. doi:10.1001/jama.1984.03340470049026

Ingestion of large amounts of some pain-relieving drugs over prolonged periods has been shown to be associated with the development of one type of kidney disease that can lead to kidney failure. Since this problem was first reported in the 1950s, analgesic-associated kidney disease has become recognized as a serious, costly, and potentially preventable and treatable health problem. While research has shown an association of analgesic ingestion with kidney disease, there continues to be debate about the specific drugs that cause it, the mechanisms by which renal damage occurs, and the extent to which this illness may contribute to the overall burden of chronic renal disease in our society. The distribution and prevalence of analgesic-associated kidney disease appear to vary widely in different countries of the world and within the countries where it has been shown to occur.

In an effort to resolve some of the questions about this type of kidney disease, the National Institutes of Health convened a Consensus Development Conference on Analgesic-Associated Kidney Disease from Feb 27 through 29, 1984. After 1 1/2 days of scientific presentations by experts of the available data about the problem, a Consensus Panel including representatives of the fields of nephrology, pathology, internal medicine, family medicine, pharmacology, biostatistics, epidemiology, and the general public considered the scientific evidence and agreed on answers to the following questions:

  1. Can analgesics, alone or in combination, cause kidney disease and chronic kidney failure? What evidence supports these conclusions?

  2. What are the scope and characteristics of the problem of kidney disease caused by excessive use of analgesics in the United States and in other countries?

  3. What causes analgesic-associated kidney disease?

  4. What factors increase the risk of occurrence of analgesic-associated kidney disease?

  5. Can analgesic-associated kidney disease be prevented?

  6. What treatment strategies are appropriate?

  7. What are the directions for future research?

Panel's Conclusions  Considerable evidence indicates that combinations of antipyretic analgesics, taken in large doses over a prolonged period, cause a specific form of kidney disease and chronic renal failure. Persons so exposed may be more susceptible to the subsequent development of uroepithelial tumors. In contrast, there is little evidence that preparations containing a single analgesic agent have been similarly abused and similarly harmful.The occurrence of analgesic-associated nephropathy shows striking geographical differences. Such differences may be related, at least in part, to regional variations in the habitual consumption of antipyretic-analgesic mixtures. The pathogenesis of the condition is uncertain but may involve a direct cytotoxic action of the analgesics on the renal papilla, perhaps enhanced by ischemia.The sustained use of mixtures of antipyretic analgesics in large doses is not advisable. Serious consideration should be given to limiting over-the-counter products to those containing a single antipyretic-analgesic agent.