This paper presents a brief review of the initial investigative efforts in three countries--"Yugoslavia", Bulgaria and Romania--on Balkan endemic nephropathy. There is now expert agreement that the ...disease represents an unusual type of chronic interstitial nephropathy of unknown aetiology. The epidemiological and histopathological data are summarized very briefly. The clinical symptoms and signs and the diagnostic approach to the disease are presented in greater detail. The possibilities of an early diagnosis in the latent, subclinical and early phases of the disease are discussed, together with the importance of the detection of a tubular type of proteinuria and enzymuria as a diagnostic aid.
Mycotoxins are secondary metabolites of a variety of moulds having toxic properties in human, animal and plant organisms. Some of them have proven or suspected carcinogenic potential. Thus aflatoxin ...B sub(1) and M sub(1), ochratoxin A, and fumonisin B sub(1) are proven carcinogens in some experimental animals. Aflatoxins are produced by moulds which are common for the tropical climate, whereas fungi-producing ochratoxins and fumonisins are present everywhere. Among numerous aflatoxins, aflatoxin B sub(1) is the most toxic and so is ochratoxin A among ochratoxins and fumonisin B sub(1) among fumonisins. Aflatoxins form DNA adducts, which may serve as good biological markers for the exposure to aflatoxins. Aflatoxins primarily affect liver and kidney, causing cirrhosis which ends with liver cancer. Ochratoxin A is a potent nephrotoxic agent, affecting primary tubules and leading to functional impairment and development of fibrosis. Results of many experiments have shown strong resemblance to human kidney disease, known as endemic nephropathy. It is rather common that endemic nephropathy is associated with otherwise rare urothelial tumours. Ochratoxin A is found in many samples of human food and animal feed, but also in human blood. While it is frequent in urban population, but in low concentrations, in rural areas with endemic nephropathy both the frequency and the level are significantly higher. Fumonisins disturb some essential physiological processes by inhibiting the sphingomyelin metabolism, which leads to detectable changes in the sfinganine-sfingosine ratio. This finding may be useful in assessing exposure to fumonisins. Taking into account the potential long-term effect of fumonisins, there are valid indications that fumonisin B sub(1) may be associated with an excessive incidence of oesophageal cancer in several regions in the world.
Balkan endemic nephropathy is a noninflammatory bilateral kidney lesion that affects rural populations in several circumscribed areas of the Balkans. Its etiology is still not understood, but ...recently it has been associated with exposure to nephrotoxic mycotoxins. It has been known to be present since the mid-1950s in 14 villages in an endemic area of Croatia, where approximately 10,000 people are at risk. Its prevalence fluctuates between 0.4 and 8.3%, showing a slight decline in recent years, but it has not disappeared from any of the endemic villages. The occurrence of the disease in several ethnic groups contradicts the hypothesis of a primary hereditary basis for Balkan endemic nephropathy. Recently, evidence has been found of an extremely high incidence of urinary tract tumours in the endemic area, and particularly of urothelial tumours of the pelvis and ureter. There may therefore be a common causative agent for these two rare diseases.
Ochratoxin A is a mycotoxin with pronounced nephrotoxic potency in all species of single-stomach animals studied; it is a major disease determinant of porcine nephropathy and a disease occurring ...endemically in several countries. This disease is comparable with Balkan (endemic) nephropathy, suggesting a common causal relationship. Ochratoxin A has been found in foodstuffs in many countries, but the highest frequency of ochratoxin A contamination in foods (10.3% of 1,553 samples of foodstuffs) was encountered in an area of Yugoslavia, where Balkan (endemic) nephropathy is prevalent. Detection of ochratoxin A in human blood samples confirmed the prevalent exposure to this food contaminant. Relative risk calculations indicated a tendency to an association between this mycotoxin and Balkan (endemic) nephropathy, supporting the hypothesis of a causal role of ochratoxin A in this disease.
Ochratoxin A is a nephrotoxic fungal metabolite (mycotoxin) occurring in foodstuffs. The compound is causally associated with mycotoxic porcine nephropathy, a disease comparable with a human kidney ...disease, Balkan (endemic) nephropathy. A survey of 768 samples of foodstuffs (cereals and bread), locally produced in an area of Yugoslavia where Balkan (endemic) nephropathy is prevalent, has revealed that ochratoxin A is constantly present in parts of foodstuffs. The mean frequency of ochratoxin A contamination of cereals in the study period was 8.7 per cent, but a pronounced annual variation was encountered, with frequencies of contamination up to 43 per cent. These contamination frequencies are higher than those reported elsewhere for foodstuffs for human consumption. Thus further evidence is provided to support the hypothesis that ochratoxin A might by a disease determinant of Balkan (endemic) nephropathy.
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