Carcinoma aristolochic acid nephropathy

Association with urinary tract carcinomas Pathogenesis The role of aristolochic acids Experimental aristolochic acid nephropathy Conclusion... 

Lemy A, Wissing KM, Rorive S, Zlotta A, Roumeguere T, Muniz Martinez MC, Decaestecker C, Salmon I, Abramowicz D, Vanherweghem JL, Nortier J. Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy a case series with 15-year follow-up. Am J Kidney Dis 2008 51 471 -477... 

One patient who had a urothehal malignancy 6 years after the onset of Chinese herb nephropathy later developed a breast carcinoma that metastasised to the liver (31). The urothelial mahgnancy contained aristolochic acid-DNA adducts and mutations in the p53 gene, and the same mis-sense mutation in codon 245 of exon 7 of p53 was found in DNA from the breast and liver tumors. However, DNA extracted from the urothelial tumor also showed a mutation in codon 139 of exon 5, which was not present in the breast and liver. 

Although the precise mechanism of aristolochic acid-induced nephropathy and urothelial carcinoma is yet to be characterized, recent data indicate direct DNA damage may be the cause. The major components of aristolochic acid are metabolized to mutagenic compounds called aristolactam I and aristolactam II, respectively, which have been demonstrated to form DNA adducts in humans. Direct cellular toxicity is an unlikely mechanism of injury since the onset is delayed and progression of renal failure continues after aristolochic acid exposure. ... 

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