Nortier Joëlle, Pozdzik Agnieszka, Roumeguere Thierry, Vanherweghem Jean-Louis
Service de néphrologie, dialyse et transplantation rénale, hôpital Érasme, université Libre de Bruxelles, route de Lennik, 808, 1070 Bruxelles, Belgique; Laboratoire de néphrologie expérimentale, faculté de médecine, campus Érasme, CP-626, route de Lennik, 808, 1070 Bruxelles, Belgique.
Service de néphrologie, dialyse et transplantation rénale, hôpital Érasme, université Libre de Bruxelles, route de Lennik, 808, 1070 Bruxelles, Belgique; Laboratoire de néphrologie expérimentale, faculté de médecine, campus Érasme, CP-626, route de Lennik, 808, 1070 Bruxelles, Belgique.
Nephrol Ther. 2015 Dec;11(7):574-88. doi: 10.1016/j.nephro.2015.10.001. Epub 2015 Oct 26.
Aristolochic acid nephropathy is a renal disease of toxic origin characterized by a progressive interstitial fibrosis and frequently associated with urinary tract cancer. It was initially reported in Belgium after the intake of slimming pills containing root extracts of a Chinese herb, Aristolochia fangchi. In the following decades, numerous cases have been reported worldwide, particularly in Asian countries. Several experimental models of aristolochic acid nephropathy (AAN) have been designed. They confirm the causal link between AA exposure and the onset of acute and chronic renal toxicity, as well as urinary tract cancer. These experimental models offer the opportunity to study the mechanisms of renal interstitial fibrosis and carcinogenesis. In terms of public health, the history of this nephropathy demonstrates that it is mandatory to submit all "natural medicinal products" to the same controls of efficacy, toxicity and conformity applied to the classical drugs derived from the pharmaceutical producers. Any unusual observation of renal failure and/or cancer of the urinary tract should lead to a questioning about any prior exposure to AA. The confirmation of the ingestion of AA containing compounds by phytochemical analysis is not always feasible. However, the renal biopsy remains a crucial diagnostic point through the demonstration of a hypocellular interstitial fibrosis with a decreasing corticomedullary gradient, mostly in advanced cases of kidney disease. Moreover, the detection of AA-related DNA adducts within a renal or urothelial tissue sample could confirm the prior AA exposure. The persistence of these specific DNA adducts in renal tissue is very long (up to 20 years). Finally, considering the highly carcinogenic properties of AA, a systematic endo-urological screening is absolutely necessary.
马兜铃酸肾病是一种由毒素引起的肾脏疾病,其特征为进行性间质纤维化,且常与尿路癌相关。该疾病最初在比利时被报道,起因是服用了含有中药广防己根提取物的减肥药。在接下来的几十年里,全球范围内都有大量病例报道,尤其是在亚洲国家。目前已经设计了几种马兜铃酸肾病(AAN)的实验模型。这些模型证实了接触马兜铃酸与急慢性肾毒性以及尿路癌发病之间的因果关系。这些实验模型为研究肾间质纤维化和致癌作用机制提供了契机。从公共卫生角度来看,这种肾病的历史表明,必须对所有“天然药物产品”进行与制药生产商生产的传统药物相同的疗效、毒性和合规性控制。任何关于肾衰竭和/或尿路癌的异常观察都应引发对之前是否接触过马兜铃酸的质疑。通过植物化学分析来确认是否摄入了含马兜铃酸的化合物并不总是可行的。然而,肾活检仍然是一个关键的诊断要点,通过显示细胞减少的间质纤维化以及皮质髓质梯度降低来诊断,这在大多数晚期肾病病例中较为常见。此外,在肾组织或尿路上皮组织样本中检测与马兜铃酸相关的DNA加合物可以确认之前是否接触过马兜铃酸。这些特定的DNA加合物在肾组织中的持续时间很长(长达20年)。最后,考虑到马兜铃酸具有高度致癌性,系统的腔内泌尿外科筛查绝对必要。