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Arch Toxicol (2016) 90:25952615 DOI 10.1007/s00204-016-1819-3
REVIEW ARTICLE
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Web End = Balkan endemic nephropathy: an update on its aetiology
Marie Stiborov1 Volker M. Arlt2,3 Heinz H. Schmeiser4
Abstract Balkan endemic nephropathy (BEN) is a unique, chronic renal disease frequently associated with upper urothelial cancer (UUC). It only affects residents of specic farming villages located along tributaries of the Danube River in Bosnia-Herzegovina, Croatia, Macedonia, Serbia, Bulgaria, and Romania where it is estimated that ~100,000 individuals are at risk of BEN, while ~25,000 have the disease. This review summarises current ndings on the aetiology of BEN. Over the last 50 years, several hypotheses on the cause of BEN have been formulated, including mycotoxins, heavy metals, viruses, and trace-element insufciencies. However, recent molecular epidemiological studies provide a strong case that chronic dietary exposure to aristolochic acid (AA) a principal component of Aristolochia clematitis which grows as a weed in the wheat elds of the endemic regions is the cause of BEN and associated UUC. One of the still enigmatic features of BEN that need to be resolved is why the prevalence of BEN is only 37 %. This suggests that individual genetic susceptibilities to AA exist in humans.
* Marie Stiborov [email protected]
1 Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic
2 Analytical and Environmental Sciences Division, MRC-PHE Centre for Environmental and Health, Kings College London, 150 Stamford Street, London SE1 9NH, UK
3 NIHR Health Protection Research Unit in Health Impactof Environmental Hazards at Kings College Londonin partnership with Public Health England, FranklinWilkins Building, 150 Stamford Street, London SE1 9NH, UK
4 Division of Radiopharmaceutical Chemistry (E030), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Received: 17 June 2016 / Accepted: 4 August 2016 / Published online: 19 August 2016 The Author(s) 2016. This article is published with open access at Springerlink.com
In fact dietary ingestion of AA along with individual genetic susceptibility provides a scenario that plausibly can explain all the peculiarities of BEN such as geographical distribution and high risk of urothelial cancer. For the countries harbouring BEN implementing public health measures to avoid AA exposure is of the utmost importance because this seems to be the...