Pathomorphology of Balkan endemic nephropathy

Vukelić, Mato; Šoštarić, Branko; Belicza, Mladen

doi:10.1016/0278-6915(92)90033-h

Cited by 50 publications

(25 citation statements)

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“…Creatinine clearance rates and urinary specific gravity are markedly reduced. The malignant tumors of the upper urinary tract that often accompany BEN are extremely aggressive in nature 43,44 and some studies have indicated a very slightly higher incidence of the disease in females. Although a direct link between BEN/UT and OTA remains to be established, epidemiological data correlates a moderate increase in serum OTA levels with a significantly higher incidence of nephropathy and urothelial tumors in humans.…”

Section: E O'brien and D R Dietrichmentioning

confidence: 99%

“…42 BEN is characterized by progressive tubulointerstitial nephropathy, leading to tubular atrophy, periglomerular fibrosis, and cortical cysts, inevitably progressing to degenerative and necrotic renal epithelia, hyperplastic arteriopathy, and end-stage renal failure. 41,43 The accompanying functional deficits in the early stages of the disease, which begins without an acute episode, include increased urinary concentrations of glucose, proteins, leucine aminopeptidase, and γ -glutamyl transferase, coupled with a decrease in serum cholesterol and protein concentration. Creatinine clearance rates and urinary specific gravity are markedly reduced.…”

Section: E O'brien and D R Dietrichmentioning

confidence: 99%

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Ochratoxin A: The Continuing Enigma

O'Brien

Dietrich

2005

Critical Reviews in Toxicology

357

212

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The mycotoxin ochratoxin A (OTA) has been linked to the genesis of several disease states in both animals and humans. It has been described as nephrotoxic, carcinogenic, teratogenic, immunotoxic, and hepatotoxic in laboratory and domestic animals, as well as being thought to be the probable causal agent in the development of nephropathies (Balkan Endemic Nephropathy, BEN and Chronic Interstitial Nephropathy, CIN) and urothelial tumors in humans. As a result, several international agencies are currently attempting to define safe legal limits for OTA concentration in foodstuffs (e.g., grain, meat, wine, and coffee), in processed foods, and in animal fodder. In order to achieve this goal, an accurate risk assessment of OTA toxicity including mechanistic and epidemiological studies must be carried out. Ochratoxin has been suggested by various researchers to mediate its toxic effects via induction of apoptosis, disruption of mitochondrial respiration and/or the cytoskeleton, or, indeed, via the generation of DNA adducts. Thus, it is still unclear if the predominant mechanism is of a genotoxic or an epigenetic nature. One aspect that is clear, however, is that the toxicity of OTA is subject to and characterized by large species-and sex-specific differences, as well as an apparently strict structure-activity relationship. These considerations could be crucial in the investigation of OTA-mediated toxicity. Furthermore, the use of appropriate in vivo and in vitro model systems appears to be vital in the generation of relevant experimental data. The intention of this review is to collate and discuss the currently available data on OTA-mediated toxicity with particular focus on their relevance for the in vivo situation, and also to suggest possible future strategies for unlocking the secrets of ochratoxin A.

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Section: E O'brien and D R Dietrichmentioning

confidence: 99%

Section: E O'brien and D R Dietrichmentioning

confidence: 99%

Ochratoxin A: The Continuing Enigma

O'Brien

Dietrich

2005

Critical Reviews in Toxicology

357

212

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“…Over 100 000 individuals may be at risk for developing Balkan endemic nephropathy (BEN), 1 a chronic, tubulointerstitial renal disease often accompanied by urothelial cancer, 2,3 that has a lethality of nearly 100%. 4 Prevalence in affected Balkan countries is 2-10%, 4 but incidence may be over 20%, e.g., in an area in northwestern Bosnia-Herzegovina, where .50% of patients receiving chronic dialysis have the disease.…”

Section: Introductionmentioning

confidence: 99%

Limitations and plausibility of the Pliocene lignite hypothesis in explaining the etiology of Balkan endemic nephropathy

Maharaj¹

2013

International Journal of Occupational and Environmental Health

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Background: Balkan endemic nephropathy (BEN) is a chronic, tubulointerstitial renal disease often accompanied by urothelial cancer that has a lethality of nearly 100%. Introduction: One of the many factors that have been proposed to play an etiological role in BEN is exposure to organic compounds from Pliocene lignite coal deposits via the drinking water in endemic areas. Objectives: The objective of this study was to systematically evaluate the role of the tenets of the Pliocene lignite hypothesis in the etiology of BEN in order to provide an improved understanding of the hypothesis for colleagues and patients alike. Methods: A comprehensive compilation of the possible limitations of the hypothesis, with each limitation addressed in turn is presented. Results: The Pliocene lignite hypothesis can best account for, is consistent with, or has the potential to explain the evidence associated with the myriad of factors related to BEN. Conclusions: Residents of endemic areas are exposed to complex mixtures containing hundreds of organic compounds at varying doses and their potentially more toxic (including nephrotoxic) and/or carcinogenic metabolites; however, a multifactorial etiology of BEN appears most likely.

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“…It is characterized by progressive tubulointerstitial nephropathy, leading to tubular atrophy, periglomerular fibrosis, and cortical cysts, inevitably leading to end-stage renal failure (Tatu et al, 1998). Urothelial tumors, i.e., the malignant tumors of the upper urinary tract, which often accompany BEN, are extremely aggressive in nature Vukelic et al, 1991) and some studies have suggested a slightly higher disease incidence in females.…”

Section: Ochratoxinsmentioning

confidence: 99%