title: Balkan endemic nephropathy: an update on its aetiology.
abstract: Balkan endemic nephropathy (BEN) is a unique, chronic renal disease frequently associated with upper urothelial cancer (UUC). It only affects residents of specific 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 findings 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 insufficiencies. 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 fields 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 3-7 %. This suggests that individual genetic susceptibilities to AA exist in humans. 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 best way to eradicate this once mysterious disease to which the residents of BEN villages have been completely and utterly at mercy for so long.
authors.affiliation: Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40, Prague 2, Czech Republic. stiborov@natur.cuni.cz.
authors.forename: Marie
authors.initials: M
authors.lastname: Stiborová
authors.affiliation: Analytical and Environmental Sciences Division, MRC-PHE Centre for Environmental and Health, King's College London, 150 Stamford Street, London, SE1 9NH, UK.|NIHR Health Protection Research Unit in Health Impact of Environmental Hazards at King's College London in partnership with Public Health England, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Volker M
authors.initials: VM
authors.lastname: Arlt
authors.affiliation: Division of Radiopharmaceutical Chemistry (E030), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Schmeiser
mesh_terms: D000818:Animals; D030022:Aristolochia / Q000737:chemistry / Q000254:growth & development / Q000633:toxicity; D034341:Aristolochic Acids / Q000032:analysis / Q000633:toxicity*; D001449:Balkan Nephropathy / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D002274:Carcinogens, Environmental / Q000032:analysis / Q000633:toxicity*; D015986:Confounding Factors, Epidemiologic; D018556:Crops, Agricultural / Q000254:growth & development; D004032:Diet / Q000009:adverse effects; D004351:Drug Resistance; D019353:Endemic Diseases; D005061:Europe, Eastern / Q000453:epidemiology; D019317:Evidence-Based Medicine; D005433:Flour / Q000009:adverse effects / Q000032:analysis; D005506:Food Contamination / Q000517:prevention & control; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D057685:Plant Weeds / Q000737:chemistry / Q000254:growth & development / Q000633:toxicity; D015995:Prevalence; D012306:Risk; D012639:Seeds / Q000254:growth & development; D014908:Triticum / Q000254:growth & development; D014571:Urologic Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D034341:Aristolochic Acids; D002274:Carcinogens, Environmental; C000228:aristolochic acid I
keywords: Aristolochic acid; Aristolochic acid nephropathy; Balkan endemic nephropathy; Disease aetiology; Environmental and genetic factors; Upper urothelial cancer