Is the incidence of Balkan endemic nephropathy decreasing?

Dimitrov, Plamen; Simeonov, Valeri; Ganev, Varban; Karmaus, Wilfried

doi:10.1016/s0369-8114(01)00265-6

Cited by 27 publications

(24 citation statements)

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“…This is complicated by variability in diagnosis and population migration. For this study, villages were classified as being BEN-endemic villages, if there was ever a case of the disease within the village reported in the literature (Chernozemsky et al, 1977;Tanchev, 1977;Dimitrov et al, 2001Dimitrov et al, , 2002 or through field assessments from meetings with village doctors. Villages were considered BEN villages even in situations where no current cases existed.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the hypothesis that Balkan endemic nephropathy is caused by drinking water exposure to contaminants leaching from Pliocene coal deposits

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McElmurry

Long

et al. 2006

J Expo Sci Environ Epidemiol

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Balkan endemic nephropathy (BEN) is a kidney disease that has been reported in only certain rural villages in Serbia, Bulgaria, Romania, Croatia and Bosnia. The cause of BEN remains a mystery, but researchers seem to agree that exposure to one or more environmental agents is at least partially responsible. The Pliocene lignite hypothesis suggests the disease is due to long-term exposure to polycyclic aromatic hydrocarbons (PAHs) or other toxic organic compounds that have leached into drinking water supplies from low-rank coals. Although this hypothesis has been promoted by some researchers, efforts to substantiate it have been inconclusive due to limitations in sample size and methodology. The present study was designed to further examine this hypothesis by analyzing PAHs, which were implicated in the original hypothesis, in a larger number of water samples from endemic and nonendemic villages in Bulgaria and for other chemical differences between the villages. Results show that levels of all PAHs were low, with none exceeding the drinking water standard for benzo-[a]-pyrene, the most toxic PAH, and the only one for which a maximum contaminant level (MCL) has been set for drinking water. Comparison of additional unidentified chromatographic peaks from high-pressure liquid chromatography (HPLC) technique designed to detect dissolved organic compounds (DOCs) that leach from coal failed to show higher levels in BEN villages. This study finds no basis to connect PAHs or other unknown DOCs to the etiology of BEN, and suggests that the evidence in support of the Pliocene lignite hypothesis is limited to the spatial association originally proposed.

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Section: Methodsmentioning

confidence: 99%

Evaluation of the hypothesis that Balkan endemic nephropathy is caused by drinking water exposure to contaminants leaching from Pliocene coal deposits

Voice

McElmurry

Long

et al. 2006

J Expo Sci Environ Epidemiol

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“…Decreasing numbers of BEN cases are in favor of this explanation. [3,4] If the agent is present in the environment, its concentration is much lower or human contact with the environmental toxin is much less intense. For etiological studies it would be important to identify foci where the expose is currently going on or, at least, where the agent may still be present.…”

Section: Environmentally Induced Diseasementioning

confidence: 99%

“…[1] The incidence of terminal renal failure and BEN death rates has decreased between 1978 and 1997 in the South Morava region in Serbia as well as in Bulgaria. [3,4] Extension of this trend might lead to the disappearance of BEN. However, in two endemic municipalities of the outer Belgrade area (i.e., Barajevo and Lazarevac), the number of incident BEN cases did not change over the previous three decades.…”

Section: Introductionmentioning

confidence: 99%

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

et al. 2009

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Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease associated with urothelial cancer, which affects people living in the alluvial plains along the tributaries of the Danube River. Challenges of studying BEN using the epidemiological method are multiple. The natural history from exposure to occurrence of the disease may take many years. The early stages of BEN are not easily detectable clinically, as the disease is asymptomatic until a significant decline in function occurs, and even then symptoms are usually non-specific. The natural history of BEN is complex, possibly with multiple risk factors operating both at the stage of initiation of renal damage and in its progression. In BEN, genetic susceptibility is due to multiple genes of small effects, gene-gene interactions, and gene-environment interactions of complex nature that are difficult to assess with current study designs. BEN is now kidney disease of the old people, and many risk factors for disease such as smoking, alcohol consumption, obesity, and diabetes could contribute to the kidney damage. Evidence is presented that environmental rather than genetic factors play a decisive role in the etiopathogenesis of BEN. Aristolochic acid, described as a culprit of BEN in 1959, is confirmed in 2007 by the molecular biology methods. Mycotoxins and polycyclic aromatic hydrocarbons, leached from lignites and found in the vicinity of endemic settlements, deserve further investigation. Despite advances in understanding the epidemiology of BEN, more research is needed on the patterns of BEN over time and between places, and on identifying the contributions of modifiable risk factors in initiating and hastening progression of BEN in order to improve the scope for preventing BEN. Primary prevention is still at the beginning. Knowledge accumulated in the fifty years of BEN research and new data about prevention and treatment of chronic kidney disease reveal several effective methods in secondary and tertiary prevention of BEN. Genetic epidemiology could establish the relative size of the genetic effect in relation to other sources of variation in disease risk (i.e., environmental effects such as intrauterine environment, physical and chemical effects, as well as behavioral and social aspects). Public health authorities in the several countries having aristolochic acid nephropathy should take immediate measures for reducing dietary exposure of residents to Aristolochia.

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“…Due to its high incidence, the first studies on the disease stressed not only the medical but also the socioeconomic significance of BEN for endemic foci [1, 2]. Recently, a decreasing incidence of BEN has been described in Bulgaria and around the South Morava River (Serbia) [3, 4]. In contrast, the incidence of BEN is unchanged in the Kolubara River basin (Serbia) [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Detection of Renal Dysfunctions in Family Members of Patients with Balkan Endemic Nephropathy

et al. 2005

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Background/Aim: Recent studies have questioned whether new cases of Balkan endemic nephropathy (BEN) are occurring. The aim of the present study was to find out whether new members with renal dysfunctions can be identified among family members of BEN patients from the Kolubara region. Methods: The study included 47 family members of 5 BEN patients on hemodialysis (HD) and 17 members of 3 non-BEN patients on HD. Their medical and epidemiological histories were taken, an objective survey made, and all persons were examined for global and tubular kidney function. Results: Seven BEN family members (2 with previously known BEN) had creatinine clearance (Ccr) below the 75th percentile rank according to sex and age. All non-BEN family members had normal Ccr and no evidence of previous renal disorders. Hypertension was found in 20 (43%) BEN and 6 (35%) non-BEN family members. No significant differences in the frequency of renal function disorders (proteinuria, α₁-microglobulinuria, urine specific gravity, osmolality, functional excretion of sodium, tubular phosphate resorption) or anemia were found between the groups. Renal disorders were detected in 18 BEN family members without previously detected disease, 3 of whom fulfilled criteria for a diagnosis of BEN and another 2 for BEN-suspected persons. Conclusion: New cases of BEN are still arising among the affected families in the Kolubara region.

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Is the incidence of Balkan endemic nephropathy decreasing?

Cited by 27 publications

References 0 publications

Evaluation of the hypothesis that Balkan endemic nephropathy is caused by drinking water exposure to contaminants leaching from Pliocene coal deposits

Evaluation of the hypothesis that Balkan endemic nephropathy is caused by drinking water exposure to contaminants leaching from Pliocene coal deposits

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

Detection of Renal Dysfunctions in Family Members of Patients with Balkan Endemic Nephropathy

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