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

Abstract

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.

Investigation of Organic and Inorganic Contaminants in Water Sources around Elbistan Lignite Beds

“…In almost all the water samples, phthalates, the most widespread man-made contaminants, were found. This finding is in line with the earlier studies where they found abundant and numerous phthalates (Bunnell et al, 2006;Maharaj, 2014). Bunnell et al (2006) suggested that these phthalates are mainly originated from PVC well casings and plastic parts of the pump systems.…”

“…Earlier studies indicated that, in well water samples taken from BEN endemic areas, the concentration and the number of organic compounds are higher than those of the non-endemic regions (Feder et al, 1991;Maharaj, 2014;Orem et al, 2002;2007). On the other hand, the GC-MS results of the present study revealed that the organic compound composition of all the water samples is similar to each other.…”

“…naphthalene, phenanthrene, anthracene, fluoranthene), phenolic compounds, heterocyclic compounds (N-, S-, O-containing cyclic compounds) and aliphatic compounds (Chakraborty et al, 2017;Orem et al, 1999;. Leach experiments, indeed, indicated that water can leach many aromatic organic compounds from coal (Maharaj, 2014) therefore same compounds can be found both in the waters and in the coal samples (Maharaj et al, 2013;Maharaj, 2014;Orem et al, 2002). Concentrations of organic compounds in endemic area waters were found to be very low in concentration (usually <0,1 µg/L) however both concentrations and the number of compound types are higher compared to control group samples (Finkelman, 2007;Orem et al, 1999).…”

“…Although numerous studies were done in the Balkan countries and the lignite hypothesis is one of the accepted cause of BEN (Maharaj, 2014), new studies conducted on other lignite bearing areas from different parts of the world will surely help to understand (a) if untreated waters which are being in use show the similar contamination patterns and (b) if BEN-like diseases are common in these regions as well.…”

Balkan endemic nephropathy: an update on its aetiology

“…In contrast, a study by Voice et al ( 2006 ) found no detectable levels of any of the 16 priority pollutants designated by the US Environmental Protection Agency were found in water samples throughout the Balkans, and no difference in waterborne concentrations of these pollutants between BEN and non-endemic villages (Voice et al 2006 ). These findings suggest that the Pliocene lignite hypothesis is limited to the spatial association originally proposed in BEN (Maharaj 2014 ). Therefore, exposures of individuals living in endemic areas to the compounds from the lignite deposits are not relevant for the aetiology of BEN.…”