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

Abstract

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.

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

“…The Pliocene lignite hypothesis posits that BEN is caused by long-term exposure to low concentrations of toxic organic compounds leaching into drinking water, that is used almost exclusively by the population, via groundwater from Pliocene lignites found in the vicinity of endemic settlements. 16,24,27,28 Many studies have been conducted to test the role of the Pliocene lignite hypothesis in the etiology of BEN, [27][28][29][30][31][32][33][34][35][36][37][38][39] and many characteristics of the disease have been shown to be consistent with the hypothesis. For example, of immigrants who settled into endemic areas, only after a minimum of y20 years were they likely to develop the disease, suggesting low dose exposure to, e.g., a fixed environmental factor.…”

“…However, many limitations of the hypothesis have been noted in the literature. 16,24,26,28,35,36,[40][41][42][43][44][45][46][47] In addition, criticisms of a number of previous studies that were conducted to test the hypothesis have been raised, casting doubt on its validity. For example, evaluations of the research that addressed the Pliocene lignite hypothesis concluded that the primary evidence in support of it is merely the spatial association between lignite deposits and BEN endemic villages, 41 but that the spatial correlation is nothing ''more than fortuitous.''…”

Escalating chronic kidney diseases of multi-factorial origin in Sri Lanka: causes, solutions, and recommendations

“…Worldwide, these CKDue epidemics are localised in the dry zones of agricultural societies, where the landscape is flat and the ground conditions are harsh, with little rain and prolonged dry periods and drought. Examples of somewhat similar CKDu conditions reported in other countries include Uddanam, in the agricultural belt of Andhra Pradesh [7]; unusual nephropathy, in China [8] and Nicaragua [9]; and Balkan endemic nephropathy, which affects rural villages in Serbia, Bulgaria, Romania, Croatia, and Bosnia [10,11].…”

“…In many of these regions, CKDue has been reported for more than four decades without identification of any specific causative factor(s). Although ground conditions and the histopathologic features of these CKDs are somewhat similar, the postulated causes are different amongst these countries [8,10,15,16]. While some have been attributed to natural (e.g.…”

“…Worldwide, CKD of unknown/uncertain aetiology has been reported after chronic exposure to certain heavy metals, including arsenic, cadmium, mercury, chromium, uranium, gold, platinum, silver, thallium, and antimony, as well as fluoride [4,19,20] and agrochemicals [7][8][9][10][11]. Despite the epidemiological studies carried out over the past 40 years, other than the reported associations and correlations (except arsenic in ground-water, Bihar, India), no causative factor has been identified for CKDu across the continent.…”