Balkan nephropathy etiology

Tatu C. A., Orem W. H., Feder G. L., Paunescu V., Dumitrascu V., Szilagyi D. N., Finkelman R. B., Margineanu F., and Schneider F. (2000b) Balkan endemic nephropathy etiology a link to the geological environment. Cent. Euro. J. Occupat. Environ. Med. 6(2-3), 138-150. 

The most elaborate and, seemingly consistent, hypotheses regarding etiology initially came from proponents of heredify as an explanation of fhe disease occurrence. These authors assumed that the risk of developing the disease was restricted only to specific, ethnically distinct, population groups, irrespectively of their place of birth and residence history. Wider acceptance of these hypotheses was hampered by the different perception of descriptive epidemiology of Balkan nephropathy by a majority of researchers on the topic. 

Bacteria received particular attention in initial stages of the Balkan nephropathy research but their possible etiological importance has been unanimously considered as ruled out [2]. Protozoa have never attracted any attention. 

Association of ochratoxin A with chronic interstitial nephropathy in Tunisia [41] and its relation to renal tumors [42] provides additional support for the idea of the etiological role of this mycotoxin. Other fungal toxins, as zerealenone, citrinin [43] and aflatoxin were also isolated in endemic foci. Experimental models suggested that a combination of mycotoxins, rather than a single one, might be involved in the etiology of Balkan nephropathy [44]. 

Aristolochic acid and its salts, originated from a weed, Aristolochia clematitis, have toxic and carcinogenic effects to the kidneys and urothelium [45], respectively. Ivic [46] postulated that this plant may be a cause of Balkan nephropathy, but failed to provide convincing evidence from field surveys. Evidence that A. clematitis played a central role in the etiology of Chinese herb nephropathy [47-49], a condition similar to Balkan nephropathy, initiated a second look at this previously abandoned hypothesis and it gained a lot of weight by recent data on the association between DNA adduct formation derived from AA, mutation pattern and tumour development in BEN [50] (see also chapter 33). 

Effects of non-occupational exposure to cadmium [51], itai-itai disease in particular [52, 53], were occasionally compared with kidney damage seen in Balkan nephropathy patients. In spite of some resembhng features, the idea of a common etiology between cadmium nephropathy (including itai-itai disease) and Balkan nephropathy was refuted [52, 54]. 

Apostolov K, Spasic P, Bojanic N. Evidence of a viral etiology in endemic (Balkan) nephropathy. Lancet 1975 ii 1271-3. 

Grollman AP, Shibutani S, Moriya M, Miller F, Wu L, Moll U, Suzuki N, Fernandes A, Rosenquist T, Medverec Z, Jakovina K, Brdar B, Slade N,Turesky RJ, Goodenough AK, Rieger R, Vukelic M, Jelakovic B. (2007) Aristolochic acid and the etiology of endemic (Balkan) nephropathy. PNAS 2007 104 12129-12134. 

There were about 30 scientific meetings on Balkan nephropathy. Over 500 papers on the disease were published by the year 1970 [1]. By late 1980 s, this number rose to 3000 [2]. Sociopolitical turmoil, including wars, and economical hardship prevented any serious research on the problem during the 1990 s. In spite of numerous proceedings and a large number of publications on the subject, many features of Balkan nephropathy, its etiology and natural history in particular, remained nearly as mysterious as when described in the mid-fifties. 

Balkan (or endemic) nephropathy is a chronic tubulointerstitial disease of unknown, presumably exotoxic etiology. It has been shown to exist only in some parts of the southeastern Europe. 

Toncheva D, DimitrovT, Stojanova S. Etiology of Balkan endemic nephropathy a multifactorlal disease Eur J Epidemiol. 1998 Jun 14(4) 389-94. 

The earlier literature on the association between human exposure to ochratoxin A and the occurrence of Balkan endemic nephropathy and associated urinary tract tumours was summarized in the previous evaluation (Annex 1, reference 153. Contrary to the clear causal evidence of ochratoxin A-induced nephrotoxicity and kidney carcinogenicity in rodents, the significance of ochratoxin A for human health remains unclear from the available epidemiological evidence. Moreover, ochratoxin A exposure is only one of several hypotheses concerning an environmental etiology for Balkan endemic nephropathy. 

Stefanovic, V., Toncheva, D. Atanasova, S. (2006) Etiology of Balkan endemic nephropathy and associated urothelial cancer. Am. J. Nephrol. 26, 1-11. 

Pfohl-Leszkowicz A, Petkova-Bocharova T, Chernozemsky IN, and Castegnaro M (2002) Balkan endemic nephropathy and the associated urinary tract tumours Review on etiological causes, potential role of mycotoxins. Food Additives and Contaminants 19(3) 282-302. 

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