Hranjec Tjasa, Kovac Anamarija, Kos Jelena, Mao Wenyang, Chen John J, Grollman Arthur P, Jelaković Bojan
Department of Nephrology and Arterial Hypertension, University Hospital Center Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia.
Croat Med J. 2005 Feb;46(1):116-25.
To explore the hypothesis that chronic dietary poisoning by aristolochic acid could account for the unique geographical distribution, specific pattern of tubulointerstitial fibrosis, occurrence of chronic renal insufficiency, and an increased risk of developing upper urothelial cancer, all of which are associated with endemic nephropathy.
This case-controlled epidemiologic study consisted of three groups of subjects residing in an endemic region of Croatia: (a) patients meeting WHO criteria for endemic nephropathy (n=28), (b) individuals who have been treated for renal insufficiency secondary to other forms of renal disease (n=30), and (c) apparently healthy residents of the endemic village (n= 30). A detailed questionnaire, designed to collect information on demographics, exposure to potentially toxic substances, diet, agricultural practices, and other factors potentially impacting endemic nephropathy was administered to the three study groups. The seeds of Aristolochia clematitis, obtained from plants growing in the endemic region, were extracted with ethanol and analyzed by high-performance liquid chromatography for their aristolochic acid content.
The majority of subjects, including 90% of endemic nephropathy patients, recall that the plant Aristolochia clematitis (birthwort, vucja stopa in Croatian) was frequently found in local meadows and wheat fields between 20 and 30 years ago. At that time, endemic nephropathy patients encountered Aristolochia clematitis significantly more frequently than controls (P=0.035). Since then, all three study groups reported a significant increase in the use of herbicides (P<0.001) and reduction in the prevalence of Aristolochia clematitis (P<0.001). Chemical analysis established that the seeds of A. clematitis contain 0.65% aristolochic acid. It is likely that the harvesting process used by local farmers permitted the seeds of A. clematitis to mingle with the wheat grain.
Flour used to bake bread, a dietary staple in the endemic region of Croatia, is derived from wheat grain which, in the past, is likely to have been contaminated with seeds of A. clematitis during harvesting. This observation supports the hypothesis that aristolochic acid, a major constituent of the seeds, plays a central role in the development of endemic nephropathy.
探讨马兜铃酸慢性饮食中毒是否可解释地方性肾病所特有的地理分布、肾小管间质纤维化的特定模式、慢性肾功能不全的发生以及上尿路尿路上皮癌发生风险增加，所有这些均与地方性肾病相关。
这项病例对照流行病学研究由居住在克罗地亚一个地方性肾病流行地区的三组受试者组成：(a)符合世界卫生组织地方性肾病标准的患者（n = 28），(b)因其他形式的肾脏疾病继发肾功能不全而接受治疗的个体（n = 30），以及(c)该流行村庄的表面健康居民（n = 30）。向三个研究组发放了一份详细问卷，旨在收集有关人口统计学、接触潜在有毒物质、饮食、农业实践以及其他可能影响地方性肾病的因素的信息。从流行地区生长的植物中获取的威氏马兜铃种子，用乙醇提取，并通过高效液相色谱法分析其马兜铃酸含量。
大多数受试者，包括90%的地方性肾病患者，回忆起在20至30年前，威氏马兜铃（马兜铃科植物，克罗地亚语为vucja stopa）这种植物在当地草地和麦田中经常被发现。当时，地方性肾病患者遇到威氏马兜铃的频率明显高于对照组（P = 0.035）。从那时起，所有三个研究组报告除草剂的使用显著增加（P < 0.001），威氏马兜铃的患病率降低（P < 0.001）。化学分析确定威氏马兜铃种子含有0.65%的马兜铃酸。当地农民使用的收获过程可能使威氏马兜铃种子与小麦籽粒混在一起。
用于烘焙面包的面粉是克罗地亚流行地区的主食，它来自小麦籽粒，过去在收获期间很可能被威氏马兜铃种子污染。这一观察结果支持了种子的主要成分马兜铃酸在地方性肾病发展中起核心作用的假设。
