Critical evaluation of environmental exposure agents suspected in the etiology of Balkan endemic nephropathy

Balkan endemic nephropathy (BEN), a kidney disease that occurs in rural villages in Bosnia, Bulgaria, Croatia, Romania, and Serbia, is thought to be linked to an environmental toxin. The authors review literature on proposed environmental exposure agents, report the results of field sampling and analysis studies to evaluate potentials for exposure to proposed agents, and propose criteria for future testing. They used these criteria to evaluate the evidence for suggested hypotheses, concluding that several proposed agents can be eliminated or considered unlikely based on apparent inconsistencies between clinical or epidemiologic evidence related to BEN and toxicologic or exposure evidence related to the agents. Mycotoxins and aristolochic acid are the primary targets of current toxicologic investigations, and while the evidence on exposures for both is potentially consistent, it is insufficient.