Analgesic nephropathy historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Historical Perspective

Analgesics are a class of medications widely used in the treatment of pain. They include aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), as well as the antipyretics paracetamol (known as acetaminophen in the United States) and phenacetin. Introduced in the late 19th century, phenacetin was once a common component of mixed analgesics in parts of Europe, Australia, and the United States.[1] These combined analgesics contained aspirin or other NSAID with phenacetin, paracetamol, or salicylamide, and caffeine or codeine.[2]

In the 1950s, Spühler and Zollinger reported an association between kidney injury and the chronic use of phenacetin.[3] They noted that chronic users of phenacetin had an increased risk of developing specific kidney injuries, namely renal papillary necrosis and chronic interstitial nephritis. This condition was dubbed analgesic nephropathy and was attributed to phenacetin, although no absolute causative role was demonstrated. With further reports of the increased risk of kidney injury with prolonged and excessive phenacetin use, however, phenacetin was banned in several countries between the 1960s and 1980s.[1]

As the use of phenacetin declined, so too did the prevalence of analgesic nephropathy as a cause of end-stage renal disease. Data from Switzerland, for example, demonstrated a decline in the prevalence of analgesic nephropathy among patients with end-stage renal disease, from 28% in 1981 to 12% in 1990.[4] An autopsy study performed in Switzerland suggested that the prevalence of analgesic nephropathy in the general population has likewise decreased; the prevalence was 3% in 1980 and 0.2% in 2000. While these data demonstrate that analgesic nephropathy has been all but eliminated in some regions, in other regions the condition persists. Notably, in Belgium, the prevalence of analgesic nephropathy among dialysis patients was 17.9% in 1984 and 15.6% in 1990.[5][6] Michielsen and de Schepper have suggested that analgesic nephropathy persists among Belgian dialysis patients not due to non-phenacetin analgesics, but because Belgium accepts a higher proportion of elderly patients for dialysis. According to these authors, a greater proportion have analgesic nephropathy because a greater percentage of Belgian dialysis patients have been exposed to long-term use of phenacetin.[7]


  1. 1.0 1.1 McLaughlin JK, Lipworth L, Chow WH, Blot WJ (1998). "Analgesic use and chronic renal failure: a critical review of the epidemiologic literature". Kidney Int. 54 (3): 679–86. doi:10.1046/j.1523-1755.1998.00043.x. PMID 9734593. Unknown parameter |month= ignored (help)
  2. de Broe, Marc E (2008). "Analgesic nephropathy". In Curhan, Gary C (ed.). UpToDate. Waltham, MA. |access-date= requires |url= (help)
  3. Spühler O, Zollinger HU (1953). "Die chronisch-interstitielle Nephritis". Z Klin Med (in German). 151 (1): 1–50. PMID 13137299.
  4. Brunner FP, Selwood NH (1994). "End-stage renal failure due to analgesic nephropathy, its changing pattern and cardiovascular mortality. EDTA-ERA Registry Committee". Nephrol. Dial. Transplant. 9 (10): 1371–6. PMID 7816247.
  5. Elseviers MM, de Broe ME (1994). "Analgesic nephropathy in Belgium is related to the sales of particular analgesic mixtures". Nephrol. Dial. Transplant. 9 (1): 41–6. PMID 8177475.
  6. Noels LM, Elseviers MM, de Broe ME (1995). "Impact of legislative measures on the sales of analgesics and the subsequent prevalence of analgesic nephropathy: a comparative study in France, Sweden and Belgium". Nephrol. Dial. Transplant. 10 (2): 167–74. PMID 7753450.
  7. Michielsen P, de Schepper P (2001). "Trends of analgesic nephropathy in two high-endemic regions with different legislation". J. Am. Soc. Nephrol. 12 (3): 550–6. PMID 11181803. Unknown parameter |month= ignored (help)