Acetaminophen, Apirin, and Chronic Renal Failure
Previous studies have suggested an association between the heavy consumption of non-narcotic analgesics and the occurrence of chronic renal failure. However, these studies have suffered from a variety of methodological flaws.
Methods: Fored et al (New Engl J Med 345:1801-8, 2001) conducted a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden. Face-to-face interviews were conducted in 926 patients with newly diagnosed renal failure and 998 control subjects to ascertain their life-time and current usage of analgesics. Complete data was obtained for 918 of the experimental subjects and 980 of the control subjects. Logistic-regression models were used to estimate the relative risks of disease-specific types of chronic renal failure with the use of aspirin and acetaminophen.
Results: Aspirin was used regularly by 37% of the patients with renal failure and by 19% of the controls. Acetaminophen was used regularly by 25% of the patients with renal failure and by 12% of the control subjects. Regular use of either drug alone increased the risk of chronic renal failure from any cause by a factor of 2.5. The relative risks rose with cumulative lifetime doses, with acetaminophen use having a more consistent dose-dependent curve. When the potential confounding influence of recent analgesic use was removed from the analysis, the associations were only slightly weakened.
Conclusions: These results strengthen the findings of prior studies suggesting that the use of acetaminophen and aspirin increase the risk of chronic renal failure. The major weakness of this study is that the quantification of analgesic use was completely dependent on patient recall. Other studies have shown that this method can be unreliable. Nonetheless, it would seem reasonable to assume that the rate of recall errors would be similar in the renal failure and control groups, since the renal failure was not so advanced as to affect mental status.
The findings in this study are concerning, particularly since many physicians and patients still consider acetaminophen to be relatively safe, and patients with osteoarthritis may take acetaminophen for many years to manage joint pain.
A surprising finding in this study is that chronic use of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen was not associated with worsening renal insufficiency. This suggests that aspirin and acetaminophen promote renal failure by a mechanism other than inhibition of cyclooxygenase.