Ochratoxin and Kidney Disease in the Human

Abstract

Ochratoxin A (OTA), produced by several species of Aspergillus and Penicillium, is known for its nephrotoxicity in pigs and rats. Human exposure to this toxin, essentially by consumption of contaminated food and drinks derived from cereals, could be potentially nephrotoxic. There is a paradox between the risk of OTA for human renal disease, due to the wide distribution of this mycotoxin throughout the world, and the rarity of reported cases demonstrating its role in chronic renal disease. Possible OTA-induced acute renal failure was recently reported in Italy after a farmer and his wife worked 8 hours in a granary closed for several months. Renal biopsy in the woman who developed nonoliguric acute renal failure revealed lesions of acute tubular necrosis. A strain of Aspergillus ochraceus producing OTA was isolated from the wheat. Chronic nephrotoxicity due to OTA is probably more usual and makes the diagnosis more difficult. Balkan Endemic Nephropathy, a chronic tubulo-interstitial renal disease, could be due to OTA. Epidemiologic studies showed that in areas where high OTA levels are reached in food and in the blood of the population, there is a high incidence of nephropathy and renal tumours. The demonstration of DNA adducts in kidneys of animals exposed to OTA and similar adducts in renal tissue and tumours from individuals in the endemic region of the Balkan countries highlights a new molecular epidemiological approach. Karyomegalic interstitial nephritis, characterized by karyomegaly in proximal and distal tubular epithelial cells, has been reported in nine patients. Karyomegaly could be due to an environmental toxin that interferes with DNA replication. Involvement of the oxidative pathway in genotoxicity of OTA is known and oxidant stress induces DNA damage. Therefore, karyomegaly could be a histological marker of interstitial nephritis due to OTA. In developing countries where the prevalence of end stage renal failure due to nephropathy of uncertain etiology is high. OTA and probably other mycotoxins could be major environmental factors in the occurrence of renal disease.