Intersecting Pathways: Exploring the Link Between Balkan Endemic Nephropathy and Distribution of <scp> <i>Aristolochia clematitis</i> </scp> , Air Pollution and Pliocene Lignite Coal

Balkan Endemic Nephropathy (BEN) is a chronic kidney disease with high morbidity and mortality in certain rural areas of Southeast Europe. While the exposure to Aristolochic Acids (AAs), phytotoxins from Aristolochia clematitis plant, has been confirmed as the direct cause, the potential roles of carcinogenic compounds and Polycyclic Aromatic Hydrocarbons (PAHs) originating from air pollution and Pliocene lignite coal deposits remain insufficiently explored. We applied Monte Carlo simulations to examine the co-occurrence of BEN settlements with (1) the predicted presence of A. clematitis plant species, (2) shallow lignite coal deposits, and (3) key air quality parameters (PM 2.5, PM 10, NO₂, NO_x, O₃). Our results show that A. clematitis is strongly associated with neutral or slightly alkaline soils, mild temperatures, and areas of moderate vegetation, near floodplains, agricultural land, and urban zones. The probability of A. clematitis presence was significantly higher in BEN settlements (0.55) relative to control (0.35) and random locations (0.39). BEN villages were often found within lignite deposits (25% compared to 7% for control and random locations) and were exposed to significantly elevated levels of air pollutants. The distribution of BEN areas predicted from these variables correctly identified known BEN settlements and additional regions with elevated BEN risk. These findings suggest a complex, multifactorial origin of BEN, driven by AAs but also by co-exposures to PAHs. Addressing BEN risk requires an interdisciplinary approach encompassing improved agricultural practices, targeted air quality controls, and environmental remediation to mitigate both AAs and pollutant exposures.