Scientists found no difference in the occurrence of kidney function problems between men who had or had not reported significant, long-term use of popular analgesic medications (painkillers). The study, led by Kathryn M. Rexrode, M.D, appears in the July 18 issue of the Journal of the American Medical Association (JAMA).
Previous research suggests that very high acute doses of some painkillers have been associated with impaired kidney function. Some small studies have suggested that chronic use of such medications might have negative effects on the kidneys. But the authors of the JAMA article note that some of these earlier studies had “significant methodologic limitations” that weakened the utility of their findings. Thus, Dr. Rexrode and colleagues used a very large, on-going study to evaluate possible negative effects of painkillers on kidney function.
The researchers investigated the use of analgesics by over 11,000 male physicians who were enrolled in the Physicians’ Health Study, which was conducted from 1982 through 1995. Participants completed annual questionnaires about personal characteristics such as weight, height, diet, tobacco and alcohol use, and medical history. At the end of the 14-year study period, the subjects also completed detailed questionnaires about their use of analgesic medications.
Study participants’ use of aspirin, aspirin-containing compounds, acetaminophen, acetaminophen-containing compounds, and other NSAIDs (non-steroidal anti-inflammatory drugs) were evaluated and compared with evidence of decreased kidney function. Subjects provided samples of blood at both the beginning and end of the study period, which were used to evaluate how well the kidneys were working initially and 14 years later.
Dr. Rexrode and her colleagues examined two indices of kidney function and their association with analgesic use. The first index was the amount of creatinine, a waste product produced by muscle, in the blood. Higher than normal blood levels of creatinine suggest that the kidneys are not working efficiently to remove wastes from the blood. The second indicator of kidney function is called creatinine clearance, and is a more direct indication of how quickly the kidneys remove waste products from the blood.
In general, both blood creatinine levels and creatinine clearance indicated that kidney function decreased significantly with age in these healthy men, and thus all data were adjusted to take age into account. At baseline, only 460 subjects had elevated creatinine levels; there were no significant differences in analgesic use between these men and those who had normal blood creatinine. There were 1258 men whose creatinine clearance rates were below normal at baseline. These men reported significantly lower use of acetaminophen, but similar use of other NSAIDS, as men with normal creatinine clearance levels.
At the end of the study, the investigators calculated the risk of either elevated creatinine levels or decreased creatinine clearance for men who reported using up to or more than 2500 analgesic pills over the course of the study period. For acetaminophen, the relative risk of elevated creatinine was reduced by 17 percent in men who took 2500 or more pills.
For the other NSAIDs studied, there was no significant difference in risk. Similarly, for creatinine clearance there was no significant change in risk of elevation for any of the NSAIDs.
In their discussion, the authors comment that “Because analgesic use is so common, even small increases in the RR [relative risk] of renal [kidney] dysfunction could have a significant impact on rates of renal disease in the United States.”