key: cord-008995-p89e6620
authors: Krogh, Palle; Elling, Folmer
title: FUNGAL TOXINS AND ENDEMIC (BALKAN) NEPHROPATHY
date: 1976-07-03
journal: Lancet
DOI: 10.1016/s0140-6736(76)92990-1
sha: 
doc_id: 8995
cord_uid: p89e6620

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all infants born during a two-month period in the maternity ward of our hospital. The results show (figure A) that in 122 out of 125 samples rT3 levels were 4-9 times above the normal adult range. All children were euthyroid. In the other 3 cases (figure C) the rT3 was in the normal adult range. In these cases the slightly raised serum T3 levels and the normal serum T.S.H. levels suggested that the sera were from the mother since in cord-blood serum T3 levels are highly reduced and T.S.H. concentrations are normal or increased. The error could therefore be elucidated without further blood-sampling.

The rT3 levels screened in the 122 babies contrast greatly with 2 undetectable T3 levels (figure B) found in 2 cases of congenital hypothyroidism, diagnosed at one week and six weeks after delivery. Both cases cannot be strictly compared with the results obtained at birth in cord blood. For reasons given above, however, it seems unlikely that maternal T3 could influence the level observed in cord blood.

We conclude that screening for neonatal hypothyroidism with serum T3 could be of advantage and certainly deserves further investigation. This method is simple and hardly influenced by abnormal thyroxine-binding globulin, which greatly affects serum-T levels. It is likely that such a screening done at birth would permit early detection of congenital hypothyroidism and give the affected child the best chance of avoiding mental retardation. We want to draw attention to the hypothesis that E.N. is caused by ochratoxin A or other fungal toxins, proposed at the 2nd International Symposium on Endemic Nephropathy4 and referred to in your 1973 editorial.s This hypothesis was based primarily upon the striking similarities between E.N. and ochratoxin-A-induced porcine nephropathy. Ochratoxin A is a major disease determinant of naturally occurring nephropathy in pigs6 7 and poultry.' 9 Meat of pigs and poultry exposed to ochratoxin-A-contaminated feed contains residues of ochratoxin A,10 a heat-stable metabolite. Ochratoxin A has been encountered in 10-20% of homegrown cereals and pork meat in an endemic village in Yugoslavia." In the search for an environmental cause of E.N. ochratoxin A seems a likely candidate. The possible role of fungal metabolites in the aetiology of E.N. is further supported by the highly significant correlation between excess of rainfall over evaporation in harvest and initial storage periods and the number of people who die ofE.N. during the succeeding two years, observed in all three E.N. countries (Bulgaria, Romania, and Yugoslavia)." A high water content in foodstuffs favours fungal growth and mycotoxin formation.

The possible association of pig husbandry and E.N. mentioned by Apostolov et al. would be better explained by indicting ochratoxin A residues in pork meat, and hence a higher exposure for those people who eat pork meat compared with non-consumers of pork meat (the Muslims). Furthermore, if pig-borne coronavirus were the cause of E.N., would not one expect nephropathy among workers at pig slaughterhouses all over the world?

To test the ochratoxin hypothesis information is needed on total exposure of the village population in endemic areas, based upon total diet studies. Work of this type is now in progress at the Institute for Medical Research, Zagreb. Also important in this context is the possible detection and localisation of ochratoxin A in kidneys from E.N. patients. Work of this type, by use of immunofluorescence, is now in progress at our institutes. SiR,—The concentrated form necessary for presentation of data in your excellent letters section may occasionally lead some of your readers to suspect that authors have overlooked important, and even elementary, facts. Thus Fuller and McCartney'3 find it difficult to judge the significance of our data140n serum high-density lipoprotein (H.D.L.) levels in patients with coronary heart-disease (c.H.D.) because we did not give information on other variables. In fact we did not find any significant correlation between apo-AI-containing lipoprotein particles and other relevant indices (the fact that we did not measure H.D.L. cholesterol but apo-AI-containing particles is also relevant to the interesting letter by Lopes-Virella and Colwell" Clearly, we would not have stressed the potential usefulness of H.D.L. determination if the data had suggested that quantitative H.D.L. variation largely reflects variation in other lipoprotein indices.

Fuller and McCartney question our statement that "H.D.L. concentration is to a great extent independent of lipid and lipoprotein indices usually measured". Obviously, our statement does not preclude the existence of correlations between H.D.L. level and other lipoprotein parameters. Data in the papers cited by Fuller relationship, that it "has varied between positive, negative, or non-significant". We think that our statement covers this situation adequately.

Proceedings of the Second International Symposium on Endemic Nephropathy; p. 266. Sofia

Advances of Veterinary Science and Comparative Medicine