title: 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.
abstract: 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.
authors: RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA. levine@rti.org.
authors: Keith E
authors: KE
authors: Levine
authors: RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA. jredmon@rti.org.
authors: Jennifer Hoponick
authors: JH
authors: Redmon
authors: RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors: Myles F
authors: MF
authors: Elledge
authors: Department of Medicine, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
authors: Kamani P
authors: KP
authors: Wanigasuriya
authors: RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors: Kristin
authors: K
authors: Smith
authors: RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors: Breda
authors: B
authors: Munoz
authors: Atomic Energy Authority, Wellampitiya, Sri Lanka.
authors: Vajira A
authors: VA
authors: Waduge
authors: Section of Epidemiology and Biostatistics, School of Population Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors: Roshini J
authors: RJ
authors: Periris-John
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Nalini
authors: N
authors: Sathiakumar
authors: RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors: James M
authors: JM
authors: Harrington
authors: RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors: Donna S
authors: DS
authors: Womack
authors: Department of Public Health, University of Kelaniya, Kelaniya, Sri Lanka.
authors: Rajitha
authors: R
authors: Wickremasinghe
mesh_terms: D000328:Adult; D000818:Animals; D060766:Drinking Water / Q000032:analysis; D004781:Environmental Exposure; D004784:Environmental Monitoring; D005399:Fishes; D005506:Food Contamination / Q000032:analysis; D006197:Hair / Q000737:chemistry; D006801:Humans; D008297:Male; D019216:Metals, Heavy / Q000032:analysis / Q000097:blood; D008875:Middle Aged; D012275:Oryza / Q000737:chemistry; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000453:epidemiology*; D012307:Risk Factors; D012989:Soil Pollutants / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D013188:Sri Lanka / Q000453:epidemiology; D014131:Trace Elements / Q000032:analysis / Q000097:blood; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000097:blood / Q000378:metabolism
chemical_list: D060766:Drinking Water; D019216:Metals, Heavy; D012989:Soil Pollutants; D014131:Trace Elements; D014874:Water Pollutants, Chemical
keywords: Arsenic; Biological media; CKD of non-traditional causes; CKD of unknown etiology; CKDnT; CKDu; Cadmium; Chronic kidney disease; Environmental media; Fluoride; Geochemical; Lead; Mercury; Metals; Non-communicable disease; North Central Province; Regional laboratory analysis; Risk factors; Sri Lanka