Relationship between nonphenacetin combined analgesics and nephropathy: A review

Background. The debate on the association between nonphenacetin-containing combined analgesics and renal disease has lasted for several years. Method. A peer review committee of scientists, selected jointly by the regu latory authorities of Germany, Switzerland, and Austria and the pharmaceuti cal industry was asked to critically review data on the relationship betwee n nonphenacetin combined analgesics and nephropathy. Results. The committee regarded epidemiologic evidence on nonphenacetin com bined analgesics as inconclusive because of sparse information and substant ial methodological problems. The committee also noted that a diagnosis of a nalgesic-associated nephropathy (AAN) in clinical practice usually depends on information about exposure before or in the early stages of the disease and is seldom accompanied by specific histologic evidence. The morphologic finding of papillary calcification can arise from other conditions and is n ot specific for AAN. For these reasons, the identification criteria for AAN should be reappraised with scientific methods to validate the diagnostic p rocedure. In the limited amount of experimental pharmacological data in hum ans and animals, the committee found no convincing evidence to confirm or r efute the hypothesis that nonphenacetin combined analgesics are more nephro toxic than single formulations. For caffeine taken with combined analgesics , the currently available information is not sufficient to postulate a harm ful toxicological effect. Conclusion. The committee's two main conclusions were that sufficient evide nce is absent to associate nonphenacetin combined analgesics with nephropat hy and that new studies should be done to provide appropriate data for reso lving the question.