Etiology of Balkan endemic nephropathy

巴尔干地方性肾病的病因学

• 批准号: 7050797
• 负责人: Arthur Patrick Grollman
• 金额: $ 3.76万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7050797
• 关键词: DNA; adduct; clinical research; kidney; neoplasm /cancer; tissues

DESCRIPTION (provided by applicant): Endemic (Balkan) nephropathy (EN) is a devastating disease affecting men and women living in rural areas within the Danube river basin, encompassing regions of Croatia, Bulgaria, Romania, Serbia and Bosnia. The clinical course of EN is characterized by an insidious onset, invariable progression to chronic renal failure and a strong association with urothelial cancer. Significant epidemiologic features of EN include its occurrence within certain villages; among these villages, only members of certain households are affected. It is generally believed that EN is an environmental disease related to the farm life style in endemic regions. Hypotheses have been advanced over many years to explain the etiology of EN; we are pursuing an earlier, largely ignored and untested hypothesis that seeds of Aristolochia clemantitis contaminate grain used in baking bread, a dietary staple in the endemic region. This hypothesis is supported by striking similarities between the pathophysiology of EN and the recently recognized syndrome of aristolochic acid nephropathy. Scientists based at the Univ. of Zagreb School of Medicine and Rudjer Boskovic Inst. (Zagreb), together with physicians responsible for the clinical care of patients with EN (Slavonski Brod), propose to test the aristolochic acid etiology hypothesis by conducting a molecular epidemiologic, case-control study involving 750 adult residents of three endemic villages. Residents (150) of a nearby nonendemic village serve as controls. Croatian scientists will conduct analytical studies designed to quantify the hallmark biomarker predicted by the guiding hypothesis; namely, DNA-aristolactam adducts in renal tissues and exfololiated urothelial cells in urine of patients with EN. In addition, the spectra of P53 mutations in urothelial tumor tissues obtained from long-term residents of the endemic region will be established. If our hypothesis proves to be correct, public health measures could be instituted that would lead to the eradication of EN in Croatia and throughout the Balkan region, where 100,000 persons are currently at risk. To advance that goal, we propose to initiate, in parallel, pilot epidemiologic studies in the endemic regions of Bosnia and Bulgaria where current exposure will be monitored by measuring the aristolochic acid content of flour. This FIRCA will be conducted almost entirely in Croatia, in collaboration with Dr. Bojan Jelakovic, lead foreign investigator (University of Zagreb School of Medicine) with P01 ES04068 serving as the parent grant.

描述（由申请人提供）：流行（巴尔干）肾病（EN）是一种毁灭性的疾病，影响了居住在多瑙河盆地内农村地区的男性和妇女，包括克罗地亚，保加利亚，罗马尼亚，塞尔维亚和波斯尼亚的地区。 EN的临床过程的特征是阴险的发作，慢性肾衰竭的不变进展以及与尿路上皮癌的密切相关性。 EN的重要流行病学特征包括其在某些村庄内的发生；在这些村庄中，只有某些家庭的成员受到影响。人们普遍认为，EN是一种与地方性地区农场生活方式有关的环境疾病。多年来提出了假设，以解释EN的病因。我们正在追求一个早期的，很大程度上被忽略和未经测试的假设，即阿里斯托洛希氏菌的种子污染了用于烤面包的谷物，这是地方性地区的饮食主食。该假设得到了EN的病理生理学与最近公认的Aristolochicic肾病综合征之间的惊人相似之处。位于大学的科学家。 Zagreb医学院和Rudjer Boskovic Inst。 （Zagreb）与负责EN患者（Slavonski Brod）临床护理的医生一起，建议通过进行分子流行病学，病例对照研究来测试阿里斯洛什酸病因学假说，其中涉及750个三个地方性村庄的750名成人居民。附近一个非特有村庄的居民（150）用作控制。克罗地亚科学家将进行旨在量化指导假设预测的标志性生物标志物的分析研究；也就是说，EN患者的肾脏组织中的DNA-Aristolactam加合物和尿液中的去角质尿路上皮细胞。此外，将建立从流行区域的长期居民获得的尿路上皮肿瘤组织中p53突变的光谱。如果我们的假设被证明是正确的，则可以采取公共卫生措施，这将导致在克罗地亚和整个巴尔干地区消除EN，目前有100,000人处于危险之中。为了促进这一目标，我们建议在波斯尼亚和保加利亚的流行区域并行启动试验性流行病学研究，通过测量面粉的aristolochic酸含量，可以监测当前暴露。该FIRCA将与P01 ES04068担任父母赠款，几乎将与克罗地亚几乎完全在克罗地亚进行。