An epidemiologic study of abuse of analgesic drugs: effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987)

Article Abstract:

A relationship between analgesic drugs and kidney disease has been suspected since 1953. However, a cause-and-effect relationship cannot be satisfactorily demonstrated only on the basis of correlations. For this reason, a 20-year prospective study was begun in 1968 to determine whether the use of analgesics containing phenacetin actually contributes to the development of kidney disease. The use of phenacetin, a common component of many analgesics, was determined by urinalysis; 623 women were identified who used phenacetin-containing formulations regularly, and a control group of 621 similar women was identified who used little phenacetin or none at all. The women were aged 30 to 49 at the start of the study. Within each group, urinalysis also revealed women with high and low levels of salicylates, indicative of aspirin use. Over the next 20 years, it was possible to demonstrate that the women with high levels of phenacetin had a significantly greater rate of kidney disease. Deaths due to urologic or kidney disease were over 16 times more common among the women with higher levels of phenacetin use. Elevated relative risks were also observed for cancer and cardiovascular deaths among the high-phenacetin group, and this group had an odds ratio for hypertension that was 1.6 times that of the low-phenacetin group. A strong dose-response relationship was found between the measured levels of phenacetin metabolites and the occurrence of urologic or kidney disease, which provides even stronger evidence that phenacetin use is a causal factor in the development of kidney disease. In general, however, since it is both unethical and impractical to randomize subjects and insist they take phenacetin, there will always be some questions remaining. For example, are women with a predisposition to kidney disease more likely to use analgesics for some reason? Although this possibility cannot be ruled out, the data collected in this study show that there is no association between kidney disease and salicylates, or aspirin, which would generally be taken for the same reasons as a preparation containing phenacetin. Therefore, it seems most reasonable to conclude that phenacetin use contributes directly to the development of kidney disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Aspirin, Kidney diseases, Salicylates

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Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease

Article Abstract:

Pain relievers in the nonsteroidal anti-inflammatory drug (NSAID) category have been widely prescribed in recent years, and one, ibuprofen, is now available in an over-the-counter strength. These drugs have been associated with acute kidney (renal) failure, and evidence is mounting that they can be the cause of chronic renal failure. This damage may occur in several different fashions. NSAIDs inhibit the action of prostaglandins, naturally-occurring substances with a number of effects. Diminished prostaglandin activity can decrease the amount of blood circulating to the kidneys, and for those patients in whom kidney circulation is already impaired by other disease, the added insult of decreased blood flow from inhibited prostaglandin activity can lead to kidney disease. Alternatively, NSAIDs can lead to interstitial nephritis, a type of allergic reaction that can lead to papillary necrosis, in which some of the internal structures of the kidney are damaged, which can have long-term consequences. To assess the magnitude of risk for chronic renal failure among users of NSAIDs, the medical records of 554 patients with newly diagnosed renal failure were studied and reviewed for NSAID use. Daily use of Nsaids was found to double the risk for kidney disease. Breaking the groups down by sex revealed that the deleterious effects of NSAIDs seemed to be limited to men, with their risk for kidney failure 4.6 times that of non-NSAID users. Men over 65 were found to have a 10 times greater than normal risk for kidney disease. Those patients with histories of previous heart attacks or heart failure, heavy alcohol use, or diuretic use, all had higher risks of kidney failure. The use of NSAIDs in patients who are at risk for kidney disease must be monitored carefully to avoid chronic renal failure. (Consumer Summary produced by Reliance Medical Information, Inc.)

Demographic aspects

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Analgesic use and chronic renal disease

Article Abstract:

A causal association between long-term regular use of certain analgesics and chronic renal disease is statistically established. In this statistical study, 554 adults with newly diagnosed kidney disease and 516 with no kidney disease (controls) were examined for association of analgesics (aspirin, acetaminophen, phenacetin) and kidney problems. The study uncovered that daily users of specific analgesics had significantly more cases of renal disease than those patients who made only infrequent use of them. The highest risk from daily users was with phenacetin and then acetaminophen. The investigators found no increased risk in daily aspirin users.

Evaluation, Causes of, Nonprescription drugs

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