Acetaminophen and adverse chronic renal outcomes: an appraisal of the epidemiologic evidence

This article critically reviews existing epidemiologic studies of the association between habitual acetaminophen use and chronic renal disease exclusive of neoplasia. Relevant primary studies were identified by searching the Medline database from 1966 to March 1995. There are several case reports of analgesic nephropathy following exposure to acetaminophen alone, but the accuracy with which other causes of this lesion were excluded is unclear. Three case control studies have found an increased risk (odds ratio range, 2 to 4) with habitual acetaminophen exposure for papillary necrosis, chronic renal failure, or end-stage renal disease. These studies have been open to confounding by indication. It is also difficult to determine the risk with acetaminophen alone given the prevalent use of analgesic mixtures in the populations studied. Two prospective cohort studies have suggested an increased risk of renal impairment or papillary calcification following regular analgesic exposure. One of these studies was of subjects taking phenacetin-containing analgesic mixtures and the study population of the other was too small to reach statistically significant conclusions. Recent study results have raised the possibility that habitual acetaminophen use could increase the likelihood or rate of progression of chronic renal disease in general. This review suggests that there is currently insufficient evidence to conclude that habitual use of acetaminophen as a sole analgesic is associated with an increased risk of chronic renal disease. Further research is required to examine this question. Prudence suggests that habitual use of acetaminophen should be discouraged in the absence of strong medical indications.