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No Significant Associations Found Among Healthy Men, Even Those With Moderate Analgesic Use
July 17, 2001 — The moderate use of aspirin, acetaminophen and other pain relievers is not associated with an increased risk of kidney dysfunction among healthy men, according to an article in the July 18 issue of The Journal of the American Medical Association.
Kathryn M. Rexrode, M.D., of Brigham and Women's Hospital in Boston, and colleagues analyzed data on commonly used analgesics — acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs (NSAIDs) — among 11,032 men with no prior history of renal failure (impaired kidney function with inability of the kidneys to adequately remove wastes from the bloodstream) or renal insufficiency. The men were participants in the Physicians' Health Study, which lasted 14 years, from September 1982 to December 1995, with annual follow-up.
According to background information cited in the article, high acute doses of analgesics, particularly NSAIDs, have been implicated as causes of acute renal failure, which is most commonly seen among patients with impaired kidney function. It also has been suggested that prolonged use of various analgesics may cause progressive renal damage, ultimately leading to chronic kidney failure. Some studies have shown no association between regular use of analgesics such as acetaminophen, aspirin and other NSAIDs, and chronic renal dysfunction — while other studies have shown increased risk. According to the authors, the present study is the largest cohort analysis to date of the association between analgesic use and the risk of renal dysfunction.
The authors looked at the self-reported use of analgesics among men in the study, and measured creatinine levels and creatinine clearance from blood samples provided by the men. Creatinine is a waste product of protein metabolism. An abnormally elevated blood creatinine level is seen in individuals with kidney insufficiency and kidney failure. Creatinine clearance is the amount of blood cleared of creatinine during a time period, usually expressed in milliliters per minute (mL/min).The authors defined elevated creatinine level as 1.5 milligrams per deciliter (mg/dL) or higher, and a reduced creatinine clearance as 55 mL/min or less. Self-reported use of analgesics was classified as never (less than 12 pills), 12-1,499 pills, 1,500-2,499 pills, and more than 2,500 pills."In this large cohort study of initially healthy male physicians followed up for an average of 14 years, we found no significant associations between the use of acetaminophen, aspirin, or other NSAIDs and either elevated creatinine levels or reduced creatinine clearance, even among men who used 2,500 or more pills (an average of three to four pills per week) over the study period," the authors report.A total of 460 men (4.2 percent) had elevated creatinine levels, and 1,258 men (11.4 percent) had reduced creatinine clearance. Mean (average) creatinine levels and creatinine clearances were similar among men who did not use analgesics and those who did, even at total intakes of 2,500 or more pills, according to the authors.
"Because analgesic use is so common, even small increases in the relative risk of renal dysfunction could have a significant impact on rates of renal disease in the United States. This study, however, provides reassuring evidence that there does not appear to be a strong association between chronic analgesic use and chronic renal dysfunction among a large cohort of men," the authors write.