Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi).

Background: Chinese-herb nephropathy is a progressive form of renal fibrosi s that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fang chi, which is nephrotoxic and carcinogenic. Methods: The diagnosis of a neoplastic lesion in the native urinary tract o f a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal o f the native kidneys and ureters in all our patients with end-stage Chinese -herb nephropathy who were being treated with either transplantation or dia lysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions wri tten for weight-reducing compounds during the period of exposure (1990 to 1 992) in these patients were obtained, and the cumulative doses were calcula ted. Results: Among 39 patients who agreed to undergo prophylactic surgery, ther e were 18 cases of urothelial carcinoma (prevalence, 46 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the urete r, renal pelvis, or both and 1 papillary bladder tumor. Nineteen of the rem aining patients had mild-to-moderate urothelial dysplasia, and two had norm al urothelium. All tissue samples analyzed contained aristolochic acid-rela ted DNA adducts. The cumulative dose of aristolochia was a significant risk factor for urothelial carcinoma, with total doses of more than 200 g assoc iated with a higher risk of urothelial carcinoma. Conclusions: The prevalence of urothelial carcinoma among patients with end -stage Chinese-herb nephropathy (caused by aristolochia species) is high. ( N Engl J Med 2000;342:1686-92.) (C) 2000, Massachusetts Medical Society.