title: Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: a case series with 15-year follow-up.
abstract: BACKGROUND
  Aristolochic acids are nephrotoxins and predispose to upper-tract urothelial carcinoma. The risk of bladder urothelial carcinoma after kidney transplantation and its relationship to upper-tract urothelial carcinoma is not well defined.
  
  
  METHODS
  Case series.
  
  
  METHODS
  Single-center cohort of 38 women given kidney transplants for end-stage aristolochic acid nephropathy.
  
  
  METHODS
  The prevalence of upper urinary tract urothelial carcinoma was determined by collecting pathological results of specimens obtained by means of bilateral ureteronephrectomy. We also established the cumulative incidence of bladder urothelial carcinoma in biopsies performed during prospective screening cystoscopies during a 15-year follow-up.
  
  
  RESULTS
  Upper-tract urothelial carcinoma was found in 17 patients with aristolochic acid nephropathy (44.7%). During follow-up, bladder urothelial carcinoma was diagnosed in 15 patients 68 to 169 months after cessation of aristolochic acid exposure (39.5%): 8 urothelial carcinoma in situ, 4 noninvasive low-grade papillary urothelial carcinoma, and 3 infiltrating urothelial carcinoma. 12 of 17 patients (71%) with a history of upper-tract urothelial carcinoma developed bladder urothelial carcinoma during follow-up, whereas this occurred in only 3 of 21 patients (14%) without upper-tract urothelial carcinoma (P < 0.01). Despite local and/or systemic chemotherapy, 3 patients died and 2 radical cystectomies were performed.
  
  
  CONCLUSIONS
  Small sample size of this case series.
  
  
  CONCLUSIONS
  Upper-tract and bladder urothelial carcinoma are dramatic complications in kidney transplant recipients with aristolochic acid nephropathy, confirming the carcinogenic properties of aristolochic acids. We identified upper-tract urothelial carcinoma as a potent risk factor for the subsequent development of bladder urothelial carcinoma after kidney transplantation for aristolochic acid nephropathy. Because this complication may occur years after aristolochic acid discontinuation, we suggest regular cystoscopies in addition to the bilateral ureteronephrectomy in kidney transplant recipients with aristolochic acid nephropathy.
authors.affiliation: Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Lemy
authors.forename: Karl M
authors.initials: KM
authors.lastname: Wissing
authors.forename: Sandrine
authors.initials: S
authors.lastname: Rorive
authors.forename: Alexandre
authors.initials: A
authors.lastname: Zlotta
authors.forename: Thierry
authors.initials: T
authors.lastname: Roumeguere
authors.forename: Marie-Carmen
authors.initials: MC
authors.lastname: Muniz Martinez
authors.forename: Christine
authors.initials: C
authors.lastname: Decaestecker
authors.forename: Isabelle
authors.initials: I
authors.lastname: Salmon
authors.forename: Daniel
authors.initials: D
authors.lastname: Abramowicz
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vanherweghem
authors.forename: Joëlle
authors.initials: J
authors.lastname: Nortier
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D034341:Aristolochic Acids / Q000009:adverse effects; D002273:Carcinogens; D004365:Drugs, Chinese Herbal / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000601:surgery*; D016030:Kidney Transplantation; D016685:Mitomycin / Q000008:administration & dosage; D018570:Risk Assessment; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000188:drug therapy
chemical_list: D000903:Antibiotics, Antineoplastic; D034341:Aristolochic Acids; D002273:Carcinogens; D004365:Drugs, Chinese Herbal; D016685:Mitomycin; C000228:aristolochic acid I