[Nephropathy caused by Chinese plants and aristolochic acids: from clinical observation to experimental model]

In 1992, a new type of progressive renal fibrosis was reported in patients after the intake of weight-reducing pills containing a Chinese herb (Aristolochia fangchi) rich of nephrotoxic and carcinogenic aristolochic acids (AA). Up to now, Chinese herb nephropathy (CHN), also called aristolochic acid nephropathy (AAN), has been observed in more than 100 patients in Belgium, but also in numerous patients all around the world. The main histological characteristics of CHN are tubular atrophy and interstitial fibrosis leading to severe renal functional impairment and end-stage renal failure. Urothelial carcinomas were also found in about 50% CHN patients suffering from end-stage renal failure. Experimentally, the main features of CHN were successfully reproduced after 35 days of daily AA injections to rats. Starting from this model, we demonstrated that other potential nephrotoxic substances (dexfenfluramine, diuretics) also contained in the weight-reducing pills, did not enhance the renal toxicity of AA. Interestingly, the inhibition of renin angiotensin system did not prevent the development of renal lesions, suggesting that, in contrast with other animal models, physiopathological mechanisms leading to renal fibrosis might be largely independent of angiotensin II. From clinical observations to experimental studies, we currently increased our knowledge in the understanding of pathophysiological mechanisms of nephropathies of toxic origin. Botanicals which are known or suspected to contain AA are still sold on Web sites or over-the-counter markets. It is not surprising then to find new AAN cases reported in the medical literature. Therefore, further studies are needed to elucidate pathways of AA-related nephrotoxicity and carcinogenicity in order to develop therapeutic strategies.