Chronic analgesic nephropathy is a slowly progressive renal disease resulting from daily use for many years of mixtures containing at least two analgesics (eg, aspirin, paracetamol, pyrozolones, phenacetin) and caffeine, codeine, and/or barbiturates, which may lead to psychological dependence and overuse. In the past, analgesic nephropathy was an important cause of chronic kidney disease, particularly in Australia and parts of Europe and the United States [1-3]. Previous estimates, obtained before phenacetin was removed from over-the-counter analgesics and before legislation was enacted making combined analgesics only available by prescription (in Sweden, Canada, Belgium, and Australia), suggested that analgesic nephropathy was responsible for 1 to 3 percent of cases of end-stage renal disease in the United States as a whole, up to 10 percent in areas of North Carolina, and 13 to 20 percent in Australia and some countries in Europe (such as Belgium and Switzerland).
The decrease in availability of phenacetin-containing analgesic mixtures and other combined analgesics once the risk of analgesic nephropathy was clearly established has led to a marked reduction in the number of new cases of analgesic nephropathy. In an autopsy study of 616 adults in Basle, Switzerland, the rate of analgesic nephropathy fell progressively from 3 percent in 1980 to 0.2 percent in 2000 .
The risk factors for and pathogenesis of analgesic nephropathy will be reviewed here. The clinical manifestations and diagnosis of this disorder are presented separately. (See "Clinical manifestations and diagnosis of analgesic nephropathy".)
IMPORTANCE OF PHENACETIN
Analgesic nephropathy is characterized by renal papillary necrosis and chronic interstitial nephritis that is caused by prolonged and excessive consumption of analgesic combination medications [1,5]. It is invariably due to popular proprietary mixtures containing aspirin or antipyrine in combination with phenacetin, paracetamol, or salicylamide, and caffeine or codeine. Two studies illustrate this relationship:
- A prospective, 10-year study of women found that the incidence of a rise in the plasma creatinine concentration was 12 percent in those with heavy use of analgesic mixtures versus only 1.4 percent in nonusers .
- A case control study compared 554 adults with newly diagnosed chronic renal insufficiency (plasma creatinine concentration greater than 1.5 mg/dL or 132 µmol/L) to 516 controls . The relative risk for the development of renal disease was 5.1 times control in those with daily ingestion of phenacetin-containing analgesic mixtures.