title: Relationship between nonphenacetin combined analgesics and nephropathy: a review. Ad Hoc Committee of the International Study Group on Analgesics and Nephropathy.
abstract: BACKGROUND
  The debate on the association between nonphenacetin-containing combined analgesics and renal disease has lasted for several years.
  
  
  METHODS
  A peer review committee of scientists, selected jointly by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry was asked to critically review data on the relationship between nonphenacetin combined analgesics and nephropathy.
  
  
  RESULTS
  The committee regarded epidemiologic evidence on nonphenacetin combined analgesics as inconclusive because of sparse information and substantial methodological problems. The committee also noted that a diagnosis of analgesic-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 not specific for AAN. For these reasons, the identification criteria for AAN should be reappraised with scientific methods to validate the diagnostic procedure. In the limited amount of experimental pharmacological data in humans and animals, the committee found no convincing evidence to confirm or refute the hypothesis that nonphenacetin combined analgesics are more nephrotoxic than single formulations. For caffeine taken with combined analgesics, the currently available information is not sufficient to postulate a harmful toxicological effect.
  
  
  CONCLUSIONS
  The committee's two main conclusions were that sufficient evidence is absent to associate nonphenacetin combined analgesics with nephropathy and that new studies should be done to provide appropriate data for resolving the question.
authors: Departments of Medicine and Epidemiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors: A R
authors: AR
authors: Feinstein
authors: L A
authors: LA
authors: Heinemann
authors: G C
authors: GC
authors: Curhan
authors: E
authors: E
authors: Delzell
authors: P J
authors: PJ
authors: Deschepper
authors: J M
authors: JM
authors: Fox
authors: H
authors: H
authors: Graf
authors: F C
authors: FC
authors: Luft
authors: P
authors: P
authors: Michielsen
authors: M J
authors: MJ
authors: Mihatsch
authors: S
authors: S
authors: Suissa
authors: F
authors: F
authors: Van Der Woude
authors: S
authors: S
authors: Willich
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001241:Aspirin / Q000633:toxicity*; D002110:Caffeine / Q000633:toxicity; D004338:Drug Combinations; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced*; D010615:Phenacetin; D010726:Phosphodiesterase Inhibitors / Q000633:toxicity
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D010726:Phosphodiesterase Inhibitors; D000082:Acetaminophen; D002110:Caffeine; D010615:Phenacetin; D001241:Aspirin