Urinary tract malignancy and atherosclerotic disease in patients with chronic analgesic abuse
- Marc E De Broe, MD, PhD
Marc E De Broe, MD, PhD
- Emeritus Professor of Medicine
- University of Antwerp, Belgium
In addition to renal impairment, prolonged heavy analgesic use can lead to two other major complications: urinary tract malignancy and atherosclerotic disease. The development of these conditions in patients with chronic analgesic abuse and analgesic nephropathy is discussed here. The effects of nonsteroidal antiinflammatory drugs (NSAIDs) on cardiovascular risk and the association between analgesics and the risk for hypertension are presented separately. (See "Nonselective NSAIDs: Adverse cardiovascular effects" and "COX-2 selective inhibitors: Adverse cardiovascular effects" and "NSAIDs and acetaminophen: Effects on blood pressure and hypertension".)
URINARY TRACT MALIGNANCY
Transitional cell carcinomas of the renal pelvis, ureter, and bladder (which may be multiple and bilateral) all occur with increased frequency in this setting [1-3]. The incidence of renal cell carcinoma also may be enhanced, but this remains controversial . A large meta-analysis of 20 observational studies (14 with acetaminophen, 13 with aspirin, and 5 with other nonsteroidal antiinflammatory drugs [NSAIDs]) found that acetaminophen and nonaspirin NSAIDs were associated with a significantly increased risk of developing kidney cancer (relative risk [RR] 1.28 and 1.25, respectively) .
It is estimated that a urinary tract malignancy will develop in as many as 8 to 10 percent of patients with analgesic nephropathy [1-3] but in well under 1 percent of phenacetin-containing analgesic users without kidney disease . In women under the age of 50 years, for example, analgesic abuse is the most common cause of bladder cancer, an otherwise unusual disorder in young women . The potential magnitude of this problem has also been illustrated by histologic examination of nephrectomy specimens obtained prior to renal transplantation; the incidence of urothelial atypia in this setting approaches 50 percent .
The tumors generally become apparent after 15 to 25 years of analgesic abuse , usually, but not always, in patients with clinically evident analgesic nephropathy . There is no relationship between the degree of renal failure in patients with analgesic nephropathy and the appearance of transitional cell carcinoma. Most patients are still taking the drug at the time of diagnosis, but clinically evident disease can first become apparent several years after cessation of analgesic intake and even after renal transplantation has been performed . In Australia, for example, the incidence of analgesic nephropathy declined progressively in the first 10 years after phenacetin-containing compounds were removed from over-the-counter analgesic combinations and five years after over-the-counter sales of analgesic mixtures were banned . In comparison, the incidence of urinary tract malignancy continued to rise (at a greater rate than other malignancies), a possible reflection of late phenacetin-induced injury .
It is presumed that the induction of malignancy results from the intrarenal accumulation of N-hydroxylated phenacetin metabolites that have potent alkylating action . Because of urinary concentration, the highest concentration of these metabolites will be in the renal medulla, ureters, and bladder, possibly explaining the predisposition to carcinogenesis at these sites.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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