Evaluating Weight of Evidence in the Mystery of Balkan Endemic Nephropathy

• Published in: Risk analysis Vol. 34; no. 9; pp. 1688 - 1705
• Main Authors: Bui-Klimke, Travis, Wu, Felicia
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Blackwell Publishing Ltd 01.09.2014; Wiley; John Wiley and Sons Inc
• Subjects: Analysis; Aristolochia; Aristolochic acid; Bacteria; Balkan endemic nephropathy; Balkan Nephropathy - epidemiology; Beneficiation; Biological and medical sciences; Bradford Hill criteria; Causal analysis; Cereals; Chronic illnesses; Criteria; Croatia; Diet; Diseases; Epidemiology; Evidence-Based Medicine; Exposure; Grains; Human exposure; Humans; Interstitial nephritis; Medical sciences; Metals; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; ochratoxin A; Original; Original s; Plant poisons toxicology; Public health. Hygiene-occupational medicine; Risk analysis; Risk assessment; Risk theory; Romania; Serbia; Studies; Toxicology; Toxins; Triticum aestivum; Viruses; weight of evidence; Romania; Europe, Balkans; Serbia; Bulgaria; Croatia; Interstitial nephritis; Kidney disease; Human; Ochratoxin; ochratoxin A; Urinary system disease; Mycotoxin; Evidence-based practice; Aristolochic acid; Risk analysis; Balkan endemic nephropathy; Aristolochiaceae; Balkans endemic nephropathy; Toxic plant; Toxin; Bradford Hill criteria; weight of evidence; Etiology; Dicotyledones; Angiospermae; Spermatophyta; Causality; Public health
• ISSN: 0272-4332; 1539-6924; 1539-6924
• DOI: 10.1111/risa.12239

Balkan endemic nephropathy (BEN) is a chronic, progressive wasting disease of the kidneys, endemic in certain rural regions of the Balkan nations Croatia, Serbia, Bulgaria, and Romania. It is irreversible and ultimately fatal. Though this disease was first described in the 1950s, its causes have been a mystery and a source of much academic and clinical contention. Possible etiologic agents that have been explored include exposure to metals and metalloids, viruses and bacteria, and the dietary toxins aristolochic acid (AA) and ochratoxin A (OTA). AA is a toxin produced by weeds of the genus Aristolochia, common in Balkan wheat fields. Aristolochia seeds may intermingle with harvested grains and thus inadvertently enter human diets. OTA is a mycotoxin (fungal toxin) common in many foods, including cereal grains. In this study, we analyzed the weight of evidence for each of the suspected causes of BEN using the Bradford Hill criteria (BHC): nine conditions that determine weight of evidence for a causal relationship between an agent and a disease. Each agent postulated to cause BEN was evaluated using the nine criteria, and for each criterion was given a rating based on the strength of the association between exposure to the substance and BEN. From the overall available scientific evidence for each of these suspected risk factors, AA is the agent with the greatest weight of evidence in causing BEN. We describe other methods for testing causality from epidemiological studies, which support this conclusion of AA causing BEN.