Using Mass Spectrometry to Examine the Link Between Chemical Water Quality and Kidney Disease in Rural Sri Lanka

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Chronic kidney disease of unknown etiology (CKDu) has been prevalent in the North Central Province of Sri Lanka since 1994 and has steadily increased over the last 3 decades. Currently, many researchers believe that contaminated drinking water due to agrochemical pollution is driving CKDu incidence. Suspect chemicals have included organic contaminants, heavy metals, hard water, and fluoride. However, there is a lack of studies that have tried to characterize chemical pollutants in CKDu endemic wells in Sri Lanka and compare these profiles to non-endemic wells. The objective of this dissertation was to utilize various mass spectrometric techniques and water quality monitoring methods to characterize various chemical pollutants in CKDu endemic wells. Specifically, I (1) developed a novel analytical method for the detection of a prime suspect in CKDu onset; (2) measured major chemical contaminant suspects in CKDu endemic wells and statistically assessed the relevance to CKDu incidence by comparing to non-endemic wells; and (3) utilized recent developments in high – resolution mass spectrometry and non-targeted analysis to annotate novel chemical pollutants in Sri Lankan well water and determine sources of chemical pollution on drinking wells.In Chapter 2, I developed a direct injection LC-MS/MS method for the detection of glyphosate and AMPA, the main chemical suspect for CKDu incidence and its metabolite, in hard water systems, similar to those in endemic regions of Sri Lanka. Previous detection methods either required large sample volumes, time consuming derivatization techniques, or were just not sensitive enough to detect low concentrations of the pesticide. The method I developed required little sample preparation and had the lowest detection limits for the two analytes than any other previously published method. Additionally, I was able to show that the addition of a strong chelating agent, EDTA, was able to reduce the ionic interference in MS systems caused by hard water and improve the response of anionic analytes across a wide range of water hardness, demonstrating robustness of the method. This method has implications in allowing for the environmental detection and monitoring of glyphosate, which was previously challenging to accomplish. In Chapter 3, I measured various water quality parameters hypothesized to be linked to CKDu in endemic and non-endemic wells to better understand which parameters were significant for CKDu presence. The parameters measured were: glyphosate and AMPA, water hardness, fluoride, and a suite of heavy metals. My results found significantly higher levels of glyphosate, water hardness, and fluoride in CKDu endemic wells compared to non-endemic wells. I also found endemic and non-endemic wells with heavy metals exceeding drinking water quality guidelines. Through intensive statistical analysis and calculation of Odds Ratios, glyphosate and fluoride appear to be the most significant parameters for CKDu incidence in Sri Lanka. These two parameters had significantly higher odds ratios than any other parameter measured in the study. Results demonstrate that the water hardness and abundance of metal ions in endemic regions allows glyphosate to persist in the wells and potentially induce nephrotoxicity in conjunction with high concentrations of fluoride. This is the first time a study of this size was carried out in Sri Lanka and the first to statistically link specific water quality parameters to CKDu incidence. In Chapter 4, I utilized novel high-resolution mass spectrometric and non-targeted analysis techniques to characterize contaminant profiles in endemic wells in Sri Lanka. I was able to confirm the presence of multiple pharmaceuticals, agrochemicals, polymer additives, and personal care products. Additionally, I was able to annotate probable and tentative structures within the data set acquired from endemic and non-endemic wells. A majority of these compounds have never been identified are reported to be found in Sri Lankan waters. The results demonstrate, based on the use of compounds annotated, that most of the chemical pollution in these wells is due to agricultural runoff and wastewater intrusion due to the overwhelming presence of pharmaceuticals, agrochemicals, additives, and surfactants annotated. Additionally, based on differential analysis and abundance comparisons between endemic and non-endemic wells, CKDu wells have a higher contaminant load than non-endemic wells, potentially due to the lower economic status of the North Central Province having poor drinking water infrastructure. Additionally, annotated compounds were predicted for nephrotoxicity, and compounds predicted to be nephrotoxic were significantly more abundant in endemic wells compared to non-endemic wells. In this study, I was able to use mass spectrometry to postulate main sources of pollution in Sri Lankan wells and demonstrate that endemic wells have a higher abundance of chemical pollution and potentially nephrotoxic compounds that could be related to CKDu incidence. Mass spectrometry and other analytical techniques allowed me to fully investigate the chemical contamination relevant to CKDu incidence in Sri Lanka. I measured significantly higher concentrations of glyphosate and fluoride in CKDu endemic wells, which are both suspected nephrotoxins. Additionally, I was able to calculate significant Odds Ratios for glyphosate and fluoride that demonstrate that for increasing levels of these two contaminants, the potential odds for CKDu to be present at that well significantly increases by 3 to 17-fold, respectively. Lastly, I was able to use novel high-resolution mass spectrometry and non-targeted analysis to demonstrate that the major chemical pollutant pathways in Sri Lankan wells is most likely agricultural runoff and wastewater intrusion. Additionally, I demonstrated that endemic wells appear to have a significantly higher chemical pollutant burden than non-endemic wells, with some of these pollutants potentially being nephrotoxic. These studies are some of the most comprehensive in examining chemical water quality in Sri Lanka in relation to CKDu and will aide in future research in pinpointing the exact cause for this disease in this region while also helping to advocate for cleaner drinking water in these endemic regions.





Ulrich, Jake Charles (2022). Using Mass Spectrometry to Examine the Link Between Chemical Water Quality and Kidney Disease in Rural Sri Lanka. Dissertation, Duke University. Retrieved from


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