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Evidence supporting a role of mycotoxin, in particular ochratoxin A (OA) and citrinin, in the etiology of Balkan endemic nephropathy (BEN) and associated urinary tract tumours (UTT) is reviewed. Both diseases occur in subjects born and/or living in certain rural areas where home-produced and home-stored stable foods were found to be more frequently contaminated by the OA and citrinin. OA levels in blood and urine from patients with BEN or UTT were higher than in controls. OA and possibly other mycotoxins cause endemic porcine nephropathy, a disease with morphology and clinical course similar to those of BEN. OA was carcinogenic in two rodent species with kidney as a major target organ. Animals and strains phenotype as fast metabolizers of debrisoquine were more susceptible to OA-induced carcinogenicity. Among BEN/UTT patients, a greater proportion of fast metabolizers was reported. Although no epidemiological proof of a direct causal role of mycotoxins in BEN/UTT etiology has been presented, the data accumulated so far indicate a need for prospective studies in which mycotoxins as well as other risk factors should be considered.

The number of the recorded patients with Balkan endemic nephropathy gradually decreased during the period after 1970. The author explains that by the interrupted prophylactic examinations and screenings of the population from the endemic villages during that period. The results obtained with the repeated screening, after 16 years, of the population of one hyperendemic village in Vratza district support that view point. New 74 patients with Balkan endemic nephropathy were found, 8 of them with uroepithelial tumours of the upper urinary pathways. Together with the 45 patients known so far, their total number amounts to 119, suggesting that 13,7 per cent of the population from that village has been affected by the disease. Those data convincingly suggest that the morbidity rate from Balkan endemic nephropathy in our country has not decreased - only its recording has been neglected, due to the interruption of the active search of those patients via screening of the population from the endemic settlements. That emphasizes the great importance of those investigation methods in the establishment of the real Balkan endemic nephropathy morbidity.

Total proteinuria (SSA test) and beta-2-microglobulinuria (radial immunodiffusion and radioimmunoassay tests) were measured in 60 rural patients with histologically proven tumors of the renal pelvis and ureters and as many individually matched controls. The controls were the first neighbours of the same sex, age (+/- 2 yrs), profession and migratory history. Urinalysis was performed twice with an interval of nine years (in 1973/4 and 1982/3). As expected, both proteinuria and beta-2-microglobulinuria were more frequently elevated among the patients. However, these tests were very often positive among the controls as well. Thus, the prevalence rate of hyper-beta-2-microglobulinuria, as measured by the RIA method in 1982/3, was 26.3% in the control group. A high frequency of the tubular damage, as revealed by this test, among presumably healthy persons has been attributed to the fact that most upper urothelial tumor cases come from the Balkan endemic nephropathy foci where a significant proportion of inhabitants show signs of kidney affection.

The highest relative risk of developing tumours of the renal pelvis and ureters (TPU) in a general population is confined to areas where Balkan nephropathy (BN) is endemic. Whether there is a higher frequency of cancer of any site in families with TPU cases from this BN endemic part of the world was tested by a case-referent study. A group of 65 rural patients with histologically proven TPU was individually matched with the same number of their nearest neighbours, who served as controls. Comparison of age-standardized ratios revealed that over a period of 30 years family members of the cases experienced a significantly higher risk of (non-urinary) cancer deaths than family members of their pairmates.