Quest to identify geochemical risk factors associated with chronic kidney disease of unknown etiology (CKDu) in an endemic region of Sri Lanka—a multimedia laboratory analysis of biological, food, and environmental samples
The emergence of a new form of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka’s North Central Province (NCP) has become a catastrophic health crisis. CKDu is characterized as slowly progressing, irreversible, and asymptomatic until late stages and, importantly, not attributed to diabetes, hypertension, or other known risk factors. It is postulated that the etiology of CKDu is multifactorial, involving genetic predisposition, nutritional and dehydration status, exposure to one or more environmental nephrotoxins, and lifestyle factors. The objective of this limited geochemical laboratory analysis was to determine the concentration of a suite of heavy metals and trace element nutrients in biological samples (human whole blood and hair) and environmental samples (drinking water, rice, soil, and freshwater fish) collected from two towns within the endemic NCP region in 2012 and 2013. This broad panel, metallomics/mineralomics approach was used to shed light on potential geochemical risk factors associated with CKDu. Based on prior literature documentation of potential nephrotoxins that may play a role in the genesis and progression of CKDu, heavy metals and fluoride were selected for analysis. The geochemical concentrations in biological and environmental media areas were quantified. Basic statistical measurements were subsequently used to compare media against applicable benchmark values, such as US soil screening levels. Cadmium, lead, and mercury were detected at concentrations exceeding US reference values in many of the biological samples, suggesting that study participants are subjected to chronic, low-level exposure to these elements. Within the limited number of environmental media samples, arsenic was determined to exceed initial risk screening and background concentration values in soil, while data collected from drinking water samples reflected the unique hydrogeochemistry of the region, including the prevalence of hard or very hard water, and fluoride, iron, manganese, sodium, and lead exceeding applicable drinking water standards in some instances. Current literature suggests that the etiology of CKDu is likely multifactorial, with no single biological or hydrogeochemical parameter directly related to disease genesis and progression. This preliminary screening identified that specific constituents may be present above levels of concern, but does not compare results against specific kidney toxicity values or cumulative risk related to a multifactorial disease process. The data collected from this limited investigation are intended to be used in the subsequent study design of a comprehensive and multifactorial etiological study of CKDu risk factors that includes sample collection, individual surveys, and laboratory analyses to more fully evaluate the potential environmental, behavioral, genetic, and lifestyle risk factors associated with CKDu.
KeywordsCKDu Sri Lanka Non-communicable disease Chronic kidney disease CKD of unknown etiology North Central Province Risk factors Biological media Environmental media CKD of non-traditional causes CKDnT Geochemical Regional laboratory analysis Cadmium Arsenic Lead Mercury Fluoride Metals
The authors wish to thank RTI International for providing the internal Grand Challenge research funds focusing on non-communicable diseases to allow for the drafting of this manuscript in full. We would also like to thank the following RTI employees specifically: Ms. Laura Haines for acting as the primary laboratory analyst, Ms. Ellen Bishop for reference value support, and Ms. Kibri Everett for geographic information systems support. Sample collection was supported by the University of Alabama at Birmingham, International Training and Research in Environmental and Occupational Health program, Grant Number 5 D43 TW05750, from the National Institutes of Health-Fogarty International Center (NIH-FIC).
Compliance with ethical standards
The study participant recruitment process, informed consent, and study protocol were approved by the Ethics Review Committee of the Faculty of Medicine, University of Kelaniya. Advance laboratory analyses were completed between November 2013 and March 2014 in blinded fashion with approval from the RTI Institutional Review Board.
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