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Acetaminophen Linked to Decline in Renal Function

Posted: Thursday, August 05, 2004

Lifetime use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) did not cause a decline in renal function, but acetaminophen slightly increased risk.

Analgesics are commonly used and may impair kidney function," write Gary C. Curhan, MD, ScD, from Harvard Medical School in Boston, Massachusetts, and colleagues. "However, limited prospective information is available on the long-term effects of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen on renal function."

A total of 1,697 women enrolled in the Nurses' Health Study completed a questionnaire in 1999 about lifetime use of acetaminophen, aspirin, and NSAIDs and provided blood samples in 1989 and 2000. Multivariate logistic regression was used to determine the odds of developing the main outcome of change in estimated glomerular filtration rate (GFR) for 11 years, based on lifetime analgesic intake.

Mean estimated GFR decreased from 88 + 17 mL/minute per 1.73 m2 in 1989 to 79 + 17 mL/minute per 1.73 m2 in 2000. At baseline or after 11 years, there were no substantial differences in the unadjusted or estimated GFR levels among the categories of lifetime intake for the three analgesic groups.

Aspirin and NSAID use were not associated with an increased risk of GFR decline. However, acetaminophen use was associated with an increased risk of GFR decline of at least 30 mL/minute per 1.73 m2 (P for trend = .01) and of a GFR decline of 30% or more (P for trend < .001). For women consuming more than 3,000 g of acetaminophen, multivariate-adjusted odds ratio for a decline in GFR of at least 30 mL/minute per 1.73 m2 was 2.04 (95% confidence interval, 1.28 to 3.24) compared with women consuming less than 100 g.

"Higher lifetime use of aspirin and NSAIDs is not associated with renal function decline, but high acetaminophen use may increase the risk of loss of renal function," the authors write. "The absolute risk of renal function decline due to even high lifetime analgesic intake seems to be modest."

Study limitations include inability to validate self-reported analgesic use, lack of information on the time of use for lifetime number of tablets before the first blood-sample collection, follow-up too short to assess the long-term impact of analgesic use, too few women with substantially reduced renal function to determine whether preexisting renal disease is required for an adverse impact of analgesics, lack of information on the indication for analgesic use in the past, and choice of formula for GFR affecting the interpretation of the results.

"Each of these analgesics has other potential adverse effects that should be considered when deciding whether an analgesic is needed and which one to use," the authors write. "Future studies should address whether these analgesics affect the rate of decline of renal function in individuals with established renal disease.