Urothelial Carcinoma Associated with the Use of a Chinese Herb (Aristolochia fangchi)

作者：Joëlle Nortier, Marie-Carmen Muniz Martinez, Heinz H. Schmeiser, Volker Manfred Arlt, Christian A. Bieler, Michel Pétein, Michel F. Depierreux, Luc De Pauw, Daniel A. Abramowicz, Pierre Vereerstraeten, Jean-Louis Vanherweghem · 发表于：New England Journal of Medicine · 年份：2000 · DOI：10.1056/nejm200006083422301 · 被引用次数：983 · 研究领域：Nephrotoxicity and Medicinal Plants、Infectious Disease Case Reports and Treatments、Chemotherapy-induced organ toxicity mitigation

BACKGROUND: Chinese-herb nephropathy is a progressive form of renal fibrosis 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 fangchi, which is nephrotoxic and carcinogenic. METHODS: The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for Chinese-herb weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated. RESULTS: Among 39 patients who agreed to undergo prophylactic surgery, there were 18 cases of urothelial carcinoma (prevalence, 46 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the ureter, renal pelvis, or both and 1 papillary bladder tumor. Nineteen of the remaining patients had mild-to-moderate urothelial dysplasia, and two had normal urothelium. All tissue samples analyzed contained aristolochic acid-related DNA adduc...