Role of ochratoxin in disease causation

Under experimental conditions renal damage has been induced by alimentary exposure to ochratoxin A in all single-stomach animals tested so far, including rodents, dogs, pigs and birds, and even in young ruminants still functioning as single-stomach animals. Most information on ochratoxin-induced nephropathy has been obtained in pigs during experimental studies comprising structural as well as functional changes. The renal damage is characterized morphologically by atrophy of the proximal tubules, interstitial cortical fibrosis and sclerotized glomeruli, and functionally by impairment of tubular function indicated by a decrease in TmPAH/Cin and reduced ability to produce concentrated urine. The renal effect has been observed using exposure levels of ochratoxin A in the range 200 to 4000 micrograms/kg feed. Field cases of ochratoxin-induced nephropathy in pigs have been encountered in many countries, and the disease mycotoxic porcine nephropathy (MPN) is recognized as an endemic disease entity in several northern and central European countries. Epidemics of MPN have been reported, closely related to excessive climatic conditions in periods preceding harvest. Ochratoxin A is a recognized renal carcinogen in the mouse. In female pigs exposed to alimentary ochratoxin A for 2 years, no renal cancer was observed. Ochratoxin A is metabolized and excreted relatively fast in animals, with an RL50 (residue elimination) in the pig of a few days for various tissues. Past exposure data is a requirement in retrospective epidemiological studies, but because of the short RL50 values tissue analysis for ochratoxin A is unlikely to provide that kind of data, in animals or in humans. In order to meet this demand a procedure has been developed, using renal biopsy material for activity analysis of two renal tubular enzymes, phosphoenolpyruvate carboxykinase and gamma-glutamyl transpeptidase. In pigs exposed to ochratoxin A for 1 week a 40% reduction of the enzyme activity was observed. The dose-related activity decrease of the two enzymes was accompanied by a dose-related aggravation of renal impairment, as measured by a reduction of TmPAH/Cin, suggesting that these enzymes are sensitive indicators of ochratoxin A-induced nephropathy.