Nephropathy associated with use of a Chinese herbal product containing aristolochic acid

The Medical Journal of Australia ISSN: 0025729X 4 April 2011 194 7 367-368 ©The Medical Journal of Australia 2011 www.mja.com.au Lessons from Practice nephritis leading to renal failure and severe anaem worldwide problem, but its true incidence is unknow bly underestimated, and though many cases of AA reported, to our knowledge this is the first reported ca Many countries have prohibited the production and products containing AA, but despite bans, these prod to be available through the internet or supplied throu n A (C ev I ustralia, the use of complementary and alternative medicine AM), including Chinese herbal products, is increasing. Hower, scientific evidence on the safety, efficacy and quality of CAM, as well as regulatory controls, does not appear to support such popularity. Some herbal products contain aristolochic acid (AA), which is known to be nephrotoxic and carcinogenic. Aristolochic acid nephropathy (AAN), first reported in Belgium as “Chinese herbal nephropathy”, is characterised by progressive fibrosing interstitial ia. AAN is a n and probaN have been se in Australia. sale of herbal ucts continue gh mail order. In most of the reported cases, when the patient discontinued use of the drugs their renal disease still progressed rapidly to end stage. After exposure to AA, there is also a very high incidence of uroepithelial atypia and transitional cell carcinoma, and AA is now recognised as a potent urological carcinogen. Tissue samples from some patients with AAN and urothelial malignancy have revealed AA-related DNA adducts, which may be carcinogenic through a defect of DNA repair. The pathophysiological mechanisms of AAN are still unknown. In a rat AAN model, AA renal tubule toxicity has been associated with defective activation of antioxidative enzymes and mitochondrial damage. Activation of renal fibroblasts has also been proposed as the main source of collagen deposition leading to renal interstitial fibrosis. Therapeutic strategies have consisted mainly of supportive care in patients with AAN and renal failure. One study suggested that corticosteroids may slow the rate of renal deterioration. Renal transplantation may be an effective treatment strategy for those who progress to end-stage renal failure, with one report indicating no recurrence of AAN in five such patients after a follow-up period of 1 year. The clinical course of AAN has been related to the intensity and duration of AA exposure. A mean cumulative dose of 192 g of Aristolochia fangchi was ingested by one group of patients who developed end-stage renal failure related to AA. However, in most cases, the accumulated AA dose is difficult to ascertain because the dose is recalled retrospectively by patients; the patient may ingest herbal medicines irregularly and there is no strict recommendation of dosing on labels; the AA levels in the herbal mixtures vary due to different manufacturing processes; and the quantity of AA also varies in different herbs and even in the same herb grown in different areas. Also, patient factors such as Clinical record