It has been suggested for several decades that excessive exposure to OA plays a substantive role in the development of BEN. BEN is a bilateral, noninflammatory, chronic nephropathy in which the kidneys are extremely reduced in size and weight and show diffuse cortical fibrosis. Functional impairments are characterized by progressive hypercreatininemia, hyperuremia, and hypochromic anemia. In an endemic area of Croatia, an extremely high incidence of urinary tract tumors in the endemic areas for BEN, particularly urothelial tumors of the pelvis and ureter, has been reported. In Bulgaria, 16 cases of urinary tract tumors were reported among 33 autop-sied patients with BEN. A causal relationship between exposure to OA and these human diseases is suggested by (i) similarities in the morphological and functional renal impairments induced by OA in animals and those observed in BEN and (ii) the finding that foods from the endemic areas are more heavily contaminated with OA than foods from disease-free areas. Analyses of serum samples in European countries from nearly a dozen studies revealed that blood from healthy humans was contaminated with OA at concentrations of 0.1-40 ng/ ml. The frequency of contamination of human sera, which ranged from 4 to 57%, seems to indicate continuous, widespread exposure of humans to OA.
An association between BEN and/or urinary tract tumors and OA content in blood samples has been reported. Among 61 patients with BEN and/or urinary tract tumors, 14.8% had levels of 1 or 2ng/ml and 11.5% had more than 2ng/ml OA in their blood. This proportion was significantly higher than that in a control group of 63 individuals from unaffected families in the endemic villages (7.9 and 3.2%, respectively). A case-control study provided molecular evidence for the possible role of ochratoxin in the development of urinary tract tumors in Bulgaria.
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