American Journal of Kidney Diseases
Volume 51, Issue 3 , Pages 471-477 , March 2008

Late Onset of Bladder Urothelial Carcinoma After Kidney Transplantation for End-Stage Aristolochic Acid Nephropathy: A Case Series With 15-Year Follow-up

  • Anne Lemy, MD

      Affiliations

    • Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
    • ,
  • Karl M. Wissing, MD, PhD

      Affiliations

    • Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
    • ,
  • Sandrine Rorive, MD

      Affiliations

    • Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
    • ,
  • Alexandre Zlotta, MD, PhD

      Affiliations

    • Department of Urology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
    • ,
  • Thierry Roumeguere, MD

      Affiliations

    • Department of Urology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
    • ,
  • Marie-Carmen Muniz Martinez, MD

      Affiliations

    • Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
    • ,
  • Christine Decaestecker, PhD

      Affiliations

    • Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
    • ,
  • Isabelle Salmon, MD, PhD

      Affiliations

    • Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
    • ,
  • Daniel Abramowicz, MD, PhD

      Affiliations

    • Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
    • ,
  • Jean-Louis Vanherweghem, MD, PhD

      Affiliations

    • Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
    • ,
  • Joëlle Nortier, MD, PhD

      Affiliations

    • Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
    • Corresponding Author InformationAddress correspondence to Joëlle Nortier, MD, PhD, Nephrology Department, Erasme Hospital, Université Libre de Bruxelles, 808, route de Lennik, B-1070 Brussels, Belgium.

Received 23 July 2007 ,Accepted 14 November 2007.

References 

  1. Vanherweghem JL, Depierreux M, Tielemans C, Abramowicz D. Rapidly progressive interstitial renal fibrosis in young women: Association with slimming regimen including Chinese herbs. Lancet. 1993;341:387–391
  2. Vanhaelen M, Vanhaelen-Fastre R, But P, et al. Identification of aristolochic acid in Chinese herbs. Lancet. 1994;343:174
  3. Depierreux M, Van Damme B, Vanden Houte K, et al. Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese herbs. Am J Kidney Dis. 1994;24:172–180
  4. Schmeiser HH, Bieler C, Wiessler M, et al. Detection of DNA adducts formed by aristolochic acid in renal tissue from patients with Chinese herbs nephropathy. Cancer Res. 1996;56:2025–2028
  5. Nortier JL, Muniz Martinez MC, Schmeiser HH, et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med. 2000;342:1686–1692
  6. Cosyns JP, Dehoux JP, Guiot Y, et al. Chronic aristolochic acid toxicity in rabbits: A model of Chinese herb nephropathy?. Kidney Int. 2001;59:2164–2173
  7. Debelle F, Nortier JL, De Prez E, et al. Aristolochic acids induce chronic renal failure with interstitial fibrosis in salt depleted rats. J Am Soc Nephrol. 2002;13:431–436
  8. Vanherweghem JL, Debelle F, Muniz Martinez MC, Nortier JL. Aristolochic acid nephropathy after Chinese herbal remedies. In:  De Broe ME,  Porter GA,  Bennett WM,  Verpooten GA editor. Clinical Nephrotoxins. (ed 2). London, UK: Karger; 2003;p. 579–586
  9. Gold LS, Slone TH. Aristolochic acid, an herbal carcinogen, sold on the Web after FDA alert. N Engl J Med. 2003;349:1576–1577
  10. In: International Agency for Research on Cancer (IARC): Some traditional herbal medicines, some mycotoxins, naphtalene and styrene, in IARC Monographs on the Evaluation of Carcinogenic Risks of Chemical to Humans. Lyon, France: IARC; 2002;p. 69–128
  11. Cosyns JP, Jadoul M, Squifflet JP, Wese F-X. Urothelial lesions in Chinese herb nephropathy. Am J Kidney Dis. 1999;33:1011–1017
  12. Vanherweghem JL, Tielemans C, Simon J, Depierreux M. Chinese herbs nephropathy and renal pelvic carcinoma. Nephrol Dial Transplant. 1995;10:270–273
  13. Lord GM, Cook T, Arlt VM, Schmeiser HH. Urothelial malignant disease and Chinese herbal nephropathy. Lancet. 2001;358:1515–1516
  14. Muniz Martinez M-C, Nortier J, Vereerstraeten P, Vanherweghem J-L. Progression rate of Chinese-herb nephropathy: Impact of Aristolochia fangchi ingested dose. Nephrol Dial Transplant. 2002;17:408–412
  15. Schmeiser HH, Bieler CA, Wiessler M, van Ypersele de Strihou C. Detection of DNA adducts formed by aristolochic acid in renal tissue from patients with Chinese herbs nephropathy. Cancer Res. 1996;56:2025–2028
  16. Eble J. World Health Organization Classification of Tumours (Pathology & Genetics: Tumours of the Urinary System and Male Genital Organs). Lyon, France: IARC; 2004;
  17. Sobin LH. International Union Against Cancer (TNM Classification of Malignant Tumours). Geneva, Switzerland: Wiley-Liss; 2002;
  18. Nortier JL. Upper urinary tract carcinoma after intake of Aristolochia fangchi: Value of urinary cytology in end-stage Chinese-herb nephropathy. In:  Jeffries LP editors. Trends in Cancer Research. New York, NY: Nova Science; 2006;p. 219–229
  19. Marple JT, Mac Dougall M. Development of malignancy in the end-stage renal disease patient. Semin Nephrol. 1993;13:306–314
  20. Iseki K, Osawwa A, Fukiyama K. Evidence for increased cancer deaths in chronic dialysis patients. Am J Kidney Dis. 1993;22:308–313
  21. Maisonneuve P, Agodoa L, Gellert R, et al. Cancer in patients on dialysis for end-stage renal disease: An international collaborative study. Lancet. 1999;354:93–99
  22. Buell JF, Thomas G, Gross E, Woodle S. Malignancy after transplantation. Transplantation. 2005;80:254–264
  23. Penn I. Post-transplant malignancy: The role of immunosuppression. Drug Saf. 2000;23:101–113
  24. Chapman JR, Webster AC. Cancer after renal transplantation: The next challenge. Am J Transplant. 2004;4:841–842
  25. Stewart JH, Buccianti G, Agodoa L, et al. Cancers of the kidney and urinary tract in patients on dialysis for end-stage renal disease: Analysis of data from the United States, Europe, Australia and New Zealand. J Am Soc Nephrol. 2003;14:197–207
  26. Chen KS, Lai MK, Huang CC, Chu SH. Urologic cancers in uremic patients. Am J Kidney Dis. 1995;25:694–700
  27. Grollman AP, Shibutani S, Moriya M, et al. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc Natl Acad Sci. 2007;104:12129–12134
  28. Arlt VM, Stiborova M, Schmeiser HH. Aristolochic acid as a probable human cancer hazard in herbal remedies: A review. Mutagenesis. 2002;17:265–277
  29. Mengs U, Lang W, Poch J-A. The carcinogenic action of aristolochic acid in rats. Arch Toxicol. 1982;51:107–119
  30. Schmeiser HH, Pool BL, Wiessler M. Identification and mutagenicity of metabolites of aristolochic acid formed by rat liver. Carcinogenesis. 1986;7:59–63
  31. Pezzuto JM, Swanson SM, Mar W, et al. Evaluation of the mutagenic and cytostatic potential of aristolochic acid (3,4-methylene-dioxy-8-methoxy-10-nitrophenanthrene-1-carboxylic acid) and several of its derivatives. Mutat Res. 1988;206:447–454
  32. Stiborova M, Frei E, Wiesler M, Schmeiser HH. Human enzymes involved in the metabolic activation of carcinogenic aristolochic acids: Evidence for reductive activation by cytochrome P450 1A1 and 1A2. Chem Res Toxicol. 2001;14:1128–1137
  33. Stiborova M, Frei E, Breuer A, Wiessler M. Evidence for reductive activation of carcinogenic aristolochic acids by prostaglandin H synthase–(32)P-labeling analysis of DNA adduct formation. Mutat Res. 2001;493:149–160
  34. Schmeiser HH, Scherf HR, Wiessler M. Activating mutations at codon 61 of the c-Ha-ras gene in thin-tissue sections of tumors induced by aristolochic acid in rats and mice. Cancer Lett. 1991;59:139–143
  35. Lord GM, Hollstein M, Arlt VM, et al. DNA adducts and p53 mutations in a patient with aristolochic acid associated nephropathy. Am J Kidney Dis. 2004;43:11–17
  36. Palou J, Angerri O, Segarra J, et al. Intravesical bacillus Calmette-Guerin for the treatment of superficial bladder cancer in renal transplant patients. Transplantation. 2003;76:1514–1516
  37. Dalbagni G, Russo P, Sheinfeld J, et al. Phase I trial of intravesical gemcitabine in bacillus Calmette-Guerin-refractory transitional-cell carcinoma of the bladder. J Clin Oncol. 2002;20:3193–3198

 Originally published online as doi:10.1053/j.ajkd.2007.11.015 on January 31, 2008.

PII: S0272-6386(07)01591-0

doi: 10.1053/j.ajkd.2007.11.015

American Journal of Kidney Diseases
Volume 51, Issue 3 , Pages 471-477 , March 2008

Article Tools

* Image Usage & Resolution