ANALGESIC NEPHROPATHY

Many questions about analgesic nephropathy (AN) lack clear-cut answers . We present available evidence for and against proposed answers to ma ny of these questions. These include: (1) Is acetaminophen (AC) nephro toxic when taken as the sole analgesic? (2) Is the combination of acet ylsalicylic acid (ASA) and AC more nephrotoxic than AC taken alone, an d if so, why? (3) What are the minimum doses and durations of ingestio n required to produce analgesic nephrotoxicity? (4) Is the combination of ASA and AC (a major metabolite of phenacetin) less nephrotoxic tha n that of phenacetin and ASA combined? (5) Does caffeine in combinatio n with analgesics contribute to nephrotoxicity? (6) What is the incide nce of end-stage renal disease (ESRD) due to AN? (7) What uniform diag nostic criteria should be established for AN? (8) What are the earlies t anatomic and biochemical abnormalities? (9) What are the mechanisms of renal injury? (10) Does AC cause uroepithelial neoplasia? (11) What research might be most beneficial? Based mainly on associations, some strong, we suggest that AN still exists as a cause of ESRD in the Uni ted States, where AC/ASA combinations are available over the counter, and in Canada, where they are not, We also suggest that the evidence n eeded to recommend that the AC/ASA combination be excluded from over-t he-counter analgesic preparations still has limitations, A prospective multicenter study comparing incidence related to AC/ASA in the United States and to AC in Canada and the United States may be needed to ans wer this question, For such a study to be worthwhile, an adequate inci dence in both countries is required. (C) 1998 by the National Kidney F oundation, Inc.