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.

Novel urinary biomarkers and their association with urinary heavy metals in chronic kidney disease of unknown aetiology in Sri Lanka: a pilot study

“…The role of chronic exposure to cadmium (Cd) and arsenic (As) through environmental contamination of agrochemicals remains a highly debated topic among scientists [6,[11][12]. The evidence regarding exposure to heavy metals as measured by levels of urinary excretion in patients and in controls and environmental samples is inconsistent [6,[11][12][13].Novel urinary biomarkers and their association with urinary heavy metals in chronic kidney disease of unknown aetiology in Sri Lank: a pilot study …”

Chronic kidney disease of unknown etiology and the effect of multiple-ion interactions

“…At a more typical human intake of 3 l/day, the corresponding fluoride concentrations would be 0.45 mg/l instead of 1.5 mg/l, and 0.9 µg/l of cadmium instead of 3µg/l. The data of Levine et al (2016) for the composition of water in dug wells give a maximum of 0.168 µg/l of Cd, and 2.05 mg/l of fluoride (but no standard deviations are given), indicating the daily intakes one may expect. If we use a linear model and scale the observed toxicities (in terms of weight loss per mouse) to an intake of about 1/3 the amount of water, then the weight changes for rows 2-6 of table 1 become roughly -1, -2.6, -1.3, -1.6, and -1 g/mouse, still showing significant toxicities above the likely noise threshold of the experiment.…”

“…However, the concentrations of heavy-metal toxins or pesticides found in the water or soil in the affected area were negligible or inconclusive (Jayatilake , 2013, Nanayakkara et al, 2014 in comparison to the maximum allowed levels (MALs) stipulated by WHO and other regulatory bodies. In contrast, urine samples and biopsies (Jayatilake , 2013, Dahanayake et al, 2012, Levine et al, 2016 of patients showed levels of Cd, As, and Pb well above the expected amounts. Given that most patients were in a relatively advanced state of the disease when diagnosed, these high levels merely indicated the bio-accumulation of toxins which occurs when kidneys become impaired.…”

Fertilizer usage and cadmium in soils, crops and food

“…A 90-day irrigated rice crop in the rice-growing north-central province of Sri Lanka takes up about 500 mm water [52], i.e., 5 × 10 6 litres of water per hectare as an upper bound. Typical values of Cd concentrations are 0.24 µg/L in canal water [33], or 0.11 µ g of Cd per kg of soil as reported by [39]. Hence we may take a range of values from 0.5 g -1.2 g of Cd uptake by paddy per hectare per season.…”