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Serum samples from three patients with Balkan endemic nephropathy (BEN) were inoculated intraperitoneally to guinea pigs. After a very long incubation period (58-273 days) the animals developed an experimental disease characterized by apathy, tremor, convulsions and a fatal outcome. The disease could be serially propagated, the same clinical symptoms being recorded at each of the three passages performed. The morphological features of the experimental disease included glomerular and tubular lesions and the presence of interstitial fibrous and lymphoplasmocytic reactions. Different hypotheses on the etiology of BEN are discussed.

The study was carried out in an attempt to explain the familial character of endemic Balkan nephropathy and of agglomeration of cases in certain households and in the ascendency of certain families. The hypotheses of a genetic disease or that of an infectious etiology have been taken into consideration in previous studies - by chromosomal analyses and statistical-mathematic tests of contagiousness - without being able to find arguments in support of one or the other hypotheses. This study brings important elements in favour of the possible role of ecologic factors and mainly of the hydrictoxic one, in the determination of the familial agglomerations in endemic nephropathy. Thus using radionuclear determination methods, we could demonstrate in a locality of the endemic area that around the water sources with high content of nephrotoxic oligoelements (cadmium, chromium, manganese, cobalt) there are more diseased families than around water sources poorer in these oligoelements.

The presence of antibodies to BK virus and SV40 was investigated in 63 patients with Balkan endemic nephropathy (BEN) and in 83 apparently healthy subjects from the endemic area. Serum antibodies to BK virus were detected in 95.2% of the former and in 74.7% of the latter, high antibody levels being prevalent in the age groups 41-60 years. Antibodies to SV40 were absent in the BEN patients and their frequency in the healthy subjects (27.7%) was much lower than that previously recorded in healthy persons from other zones of Romania (40%). The results obtained plead for a prevalence of BK virus infection in the endemic area with BEN.

Serum samples from patients with endemic Balkan nephropathy (EBN) were inoculated intraperitoneally to four species of laboratory animals. It was only in the guinea pig that a serially transmissible experimental disease occurred, after a long incubation period. The morphopathological features in the guinea pig were similar to those encountered in the terminal phase of human EBN. The hypothesis that EBN might be a slow virus disease is discussed.

Quantitative determinations of beta2-microglobulins were carried out in 335 urinary samples collected from 335 subjects living in villages with a high rate of morbidity and mortality from endemic Balkan nephropathy. Three months after the first determination of beta2-microglobulin excretion, blood and urine samples were obtained from 19 patients with high values and from 19 with normal values of beta2-microglobulins. The results of the biochemical and immunological investigations performed on these samples suggest that the tubular alteration is the first lesion. The autoimmune phenomena elicited by the tubular alteration may contribute, by an antigen-antibody complex disease mechanism, to the appearance of glomerular secondary lesions.