Cinical Investigation

Kidney International (1986) 30, 81–84; doi:10.1038/ki.1986.154

Phenacetin and papillary necrosis: Independent risk factors for renal pelvic cancer

Margaret McCredie, John H Stewart, Jeanette J Carter, Jennifer Turner and John F Mahony

Department of Medicine, and Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead; Department of Pathology, St. Vincent's Hospital, Darlinghurst; Renal Unit, Royal North Shore Hospital, St. Leonards, New South Wales, Australia

Correspondence: Dr J H Stewart, Department of Medicine, Westmead Hospital, Westmead, NSW 2145, Australia.

Received 17 May 1985; Revised 3 December 1985.

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Abstract

Phenacetin and papillary necrosis: Independent risk factors for renal pelvic cancer. A case–control study was undertaken to determine whether renal papillary necrosis (RPN) is an essential step in the genesis of analgesic–associated cancer of the renal pelvis (CaP). Kidneys of 66 patients (and 86 cases of renal parenchymal cancer (CaK), for comparison) were examined for evidence of RPN. Information concerning past consumption of phenacetin–containing analgesics (PhA) was obtained from all cases and 751 population controls by means of a questionnaire. Separately, RPN and regular consumption of PhA each conferred a relative risk for CaP of 3-1/2 to 7, while together they increased the risk some 20 times that for non-consumers without RPN. This suggests that each factor has independent, and when they coexist sequential, effects. The risk for CaK was doubled by regular PhA consumption but was not increased by RPN.

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References

  1. Bengtsson U, Johansson S, Angervall L: Malignancies of the urinary tract and their relation to analgesic abuse. Kidney Int 13:107–113, 1978
  2. Isaka H, Yoshi H, Otsuji A, Koike M, Nagai Y, Koura M, Sugiyasu K, Kanabayashi T: Tumors of Sprague–Dawley rats induced by long–term feeding of phenacetin. Gann 70:29–36, 1979
  3. Nanra RS, Kincaid–Smith P: Chronic effect of analgesics on the kidney. Progr Biochem Pharmacol 7:285–323, 1972
  4. Rathert P, Melchior H, Lutzeyer W: Phenacetin: a carcinogen for the urinary tract? J Urol 113:653–657, 1975
  5. Johansson S, Angervall L, Bengtsson U, Walqvist L: Uroepithelial tumours of the renal pelvis associated with the abuse of phenacetin–containing analgesics. Cancer 33:743–753, 1974
  6. Mahony JF, Storey BG, Ibanez RC, Stewart JH: Analgesic abuse, renal parenchymal disease and carcinoma of the kidney or ureter. Aust NZ J Med 7:463–469, 1977
  7. Orell SR, Nanra RS, Ferguson WW: Renal pelvic carcinoma in the Hunter Valley. Med J Aust 2:524, 555–557, 1979
  8. Burry A: Pathology of analgesic nephropathy: Australian experience. Kidney Int 13:34–40, 1978
  9. McCredie M, Ford JM, Taylor JS, Stewart JH: Analgesics and cancer of the renal pelvis in New South Wales. Cancer 49:2617–2625, 1982
  10. McCredie M, Stewart JH, Ford JM, Maclennan RA: Phenacetin-containing analgesics and cancer of the bladder or renal pelvis in women. Br J Urol 55:220–224, 1983
  11. McCredie M, Stewart JH, Ford JM: Analgesics and tobacco as risk factors for cancer of the ureter and renal pelvis in men. J Urol 130:28–30, 1983
  12. Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748, 1959 | PubMed | ChemPort |
  13. Miettinen OS: Estimability and estimation in case–referrent studies. Am J Epidemiol 103:226–235, 1976 | PubMed | ISI | ChemPort |
  14. Breslow NE, Day NE: Statistical methods in cancer research, in The Analysis of Case-Control Studies. Lyon, I ARC Scientific Publications No 32, 1980
  15. Rothman KJ, Boice JD: Epidemiologic Analysis with a Programmable Calculator. Washington, US Department of Health, Education and Welfare, 1979
  16. Burry AF, Axelsen RA, Trolove P: Analgesic nephropathy: its present contribution to the renal mortality and morbidity profile. Med J Aust 1:31–36, 1974
  17. Burry AF, Hopkins J: Phenacetin and analgesic nephropathy. Med J Aust 1:879–882, 1977
  18. McCredie M, Stewart JH, Mahony JF: Is phenacetin responsible for analgesic nephropathy in New South Wales? Clin Neph 17:134–140, 1982
  19. Arnold L, Collins C, Starmer GA: Renal papillary necrosis-the incidence at autopsy in a hospital population in Sydney. Bull Postgrad Comm Med Univ Syd 29:228–235, 1974
  20. Jacobs LA, Morris JG: Renal papillary necrosis and the abuse of phenacetin. Med J Aust 2:531–537, 1964
  21. Davies E, Kelley G: A Survey of Analgesic and Sedative Consumption in Sydney and Brisbane. Kensington, Unisearch, 1968
  22. Stewart JH: Analgesic abuse and renal failure in Australasia. Kidney Int 13:72–78, 1978
  23. Stewart JH, McCarthy SW, Storey BG, Roberts BA, Gallery E, Mahony JF: Diseases causing end–stage renal failure in New South Wales. Br Med J 1:440–443, 1975
  24. Mulder GJ, Hinson JA, Gillette JR: Generation of reactive metabolites of N-hydroxyphenacetin by glucuronidation and sulfation. Biochem Pharmacol 26:189–196, 1977
  25. Calder IC, Hart SJ, Healey K: N-Hydroxyacetaminophen: A postulated toxic metabolite of acetaminophen. J Med Chem 24:988–993, 1981
  26. McLaughlin JK, Mandel JS, Blot WJ, Schuman LM, Mehl ES, Fraumeni JF: A population–based case–control study of renal cell carcinoma. J Natl Cancer Inst 72:275–284, 1984 | PubMed | ChemPort |

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