Abstract
Chronic kidney disease of unknown etiology (CKDu) is receiving considerable attention throughout the world due to its severe threat to human health. However, the linkage between dissolved organic matter (DOM) in groundwater to CKDu is still unclear, especially at molecular level. Herein, the molecular differences of DOM between groundwaters related to CKDu (CKDu groundwater) and to non-CKDu (non-CKDu groundwater) in CKDu-prevalence areas and control area from Sri Lanka were unraveled by Fourier transform ion cyclotron resonance mass spectrometry. Compared with DOM in non-CKDu groundwater, DOM in CKDu groundwater was more unsaturated, oxidized, biologically refractory, and high-molecular-weight, and contained more aromatics (AS, 15.4%) and less aliphatics (AL, 8.2%), which was probably related to the recharge of surface water. The enrichment of biologically refractory DOM in CKDu groundwater might encompass toxic substances. Furthermore, the ratios of AS to AL (AS/AL) in groundwater were positively correlated with Ca2+, F−, and Si (r ≥ 0.66) that were generally associated with CKDu. It is explained that aromatic substances might be toxic by forming a complex with cation (Ca2+) and aliphatic substances could facilitate release of toxic anions (F−) in CKDu groundwater. According to the above findings and the receiver operating characteristic (ROC) analysis, the groundwater with AS/AL value larger than 1.43 are unsafe and likely to cause CKDu. The linkage between CKDu and specific DOM molecules provides scientific support for constructing a quick early screening of potential CKDu groundwater and helps ensure the safety of drinking water.
Graphical Abstract

This is a preview of subscription content, access via your institution.






Data Availability
All authors confirm that all data and materials support the publication and comply with field standards. The data that support the findings of this study are available from the corresponding authors upon reasonable request.
Code Availability
Not applicable.
References
Babich R, Ulrich JC, Ekanayake E, Massarsky A, De Silva P, Manage PM, Jackson BP, Ferguson PL, Di Giulio RT, Drummond IA, Jayasundara N (2020) Kidney developmental effects of metal-herbicide mixtures: implications for chronic kidney disease of unknown etiology. Environ Int 144:106019
Balasooriya S, Munasinghe H, Herath AT, Diyabalanage S, Ileperuma OA, Manthrithilake H, Daniel C, Amann K, Zwiener C, Barth JAC, Chandrajith R (2020) Possible links between groundwater geochemistry and chronic kidney disease of unknown etiology (CKDu): an investigation from the Ginnoruwa region in Sri Lanka. Expos Health 12:823–834
Begum MS, Jang I, Lee JM, Oh HB, Jin H, Park JH (2019) Synergistic effects of urban tributary mixing on dissolved organic matter biodegradation in an impounded river system. Sci Total Environ 676:105–119
Bunnell JE, Tatu CA, Lerch HE, Orem WH, Pavlovic N (2007) Evaluating nephrotoxicity of high-molecular-weight organic compounds in drinking water from lignite aquifers. J Toxicol Environ Health 70:2089–2091
Chandrajith R, Dissanayake CB, Ariyarathna T, Herath HMJMK, Padmasiri JP (2011a) Dose-dependent Na and Ca in fluoride-rich drinking water—another major cause of chronic renal failure in tropical arid regions. Sci Total Environ 409:671–675
Chandrajith R, Nanayakkara S, Itai K, Aturaliya TN, Dissanayake CB, Abeysekera T, Harada K, Watanabe T, Koizumi A (2011b) Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: geographic distribution and environmental implications. Environ Geochem Health 33:267–278
Chandrajith R, Diyabalanage S, Dissanayake CB (2020) Geogenic fluoride and arsenic in groundwater of Sri Lanka and its implications to community health. Groundw Sustain Dev 10:100359
Coble PG (1996) Characterization of marine and terrestrial DOM in seawater using excitation emission matrix spectroscopy. Mar Chem 51:325–346
Cooray T, Wei Y, Zhong H, Zheng L, Weragoda SK, Weerasooriya AR (2019) Assessment of groundwater quality in CKDu affected areas of Sri Lanka: implications for drinking water treatment. Int J Environ Res Public Health 16:1698
Dissanayake CB, Chandrajith R (2018) The hydrogeological and geochemical characteristics of groundwater of Sri Lanka. In: Groundwater of South Asia, pp 405–428
Dittmar T (2008) The molecular level determination of black carbon in marine dissolved organic matter. Org Geochem 39:396–407
Diyabalanage S, Abekoon S, Watanabe I, Watai C, Ono Y, Wijesekara S, Guruge KS, Chandrajith R (2016) Has irrigated water from Mahaweli River contributed to the kidney disease of uncertain etiology in the dry zone of Sri Lanka? Environ Geochem Health 38:679–690
Gunadasa SG, Tighe MK, Wilson SC (2021) Arsenic and cadmium and associated risk in farm soils of the dry zone sri lanka where Chronic Kidney Disease of Unknown Etiology (CKDu) is Endemic. Exposure and Health
Hagemann N, Joseph S, Schmidt HP, Kammann CI, Harter J, Borch T, Young RB, Varga K, Taherymoosavi S, Elliott KW, McKenna A, Albu M, Mayrhofer C, Obst M, Conte P, Dieguez-Alonso A, Orsetti S, Subdiaga E, Behrens S, Kappler A (2017) Organic coating on biochar explains its nutrient retention and stimulation of soil fertility. Nat Commun 8:1089
He W, Chen M, Park JE, Hur J (2016a) Molecular diversity of riverine alkaline-extractable sediment organic matter and its linkages with spectral indicators and molecular size distributions. Water Res 100:222–231
He W, Chen M, Schlautman MA, Hur J (2016b) Dynamic exchanges between DOM and POM pools in coastal and inland aquatic ecosystems: a review. Sci Total Environ 551:415–428
He C, Pan Q, Li PH, Xie W, He D, Zhang CL, Shi Q (2020) Molecular composition and spatial distribution of dissolved organic matter (DOM) in the Pearl River Estuary, China. Environ Chem 17:240–251
Hertkorn N, Benner R, Frommberger M, Schmitt-Kopplin P, Witt M, Kaiser K, Kettrup A, Hedges JI (2006) Characterization of a major refractory component of marine dissolved organic matter. Geochim Cosmochim Acta 70:2990–3010
Hettithanthri O, Sandanayake S, Magana-Arachchi D, Wanigatunge R, Rajapaksha AU, Zeng XJ, Shi QT, Guo HM, Vithanage M (2021) Risk factors for endemic chronic kidney disease of unknown etiology in Sri Lanka: retrospect of water security in the dry zone. Sci Total Environ 795:148839
Horbulyk T, Kafle K, Balasubramanya S (2021) Community response to the provision of alternative water supplies: a focus on chronic kidney disease of unknown aetiology (CKDu) in rural Sri Lanka. Water Int 46:37–58
Imbulana S, Oguma K, Takizawa S (2021) Seasonal variations in groundwater quality and hydrogeochemistry in the endemic areas of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka. Water 13:3356
Jackson K, Jonasson I, Skippen G (1978) The nature of metals—sediment—water interactions in freshwater bodies, with emphasis on the role of organic matter. Earth Sci Rev 14:97–146
Kataria A, Trasande L, Trachtman H (2015) The effects of environmental chemicals on renal function. Nat Rev Nephrol 11:610–625
Kellerman AM, Dittmar T, Kothawala DN, Tranvik LJ (2014) Chemodiversity of dissolved organic matter in lakes driven by climate and hydrology. Nat Commun 5:3804
Kellerman AM, Guillemette F, Podgorski DC, Aiken GR, Butler KD, Spencer RGM (2018) Unifying concepts linking dissolved organic matter composition to persistence in aquatic ecosystems. Environ Sci Technol 52:2538–2548
Kellerman AM, Arellano A, Podgorski DC, Martin EE, Martin JB, Deuerling KM, Bianchi TS, Spencer RGM (2020) Fundamental drivers of dissolved organic matter composition across an Arctic effective precipitation gradient. Limnol Oceanogr 65:1217–1234
Kim S, Kaplan LA, Hatcher PG (2006) Biodegradable dissolved organic matter in a temperate and a tropical stream determined from ultra-high resolution mass spectrometry. Limnol Oceanogr 51:1054–1063
Kleber M, Sollins P, Sutton R (2007) A conceptual model of organo-mineral interactions in soils: self-assembly of organic molecular fragments into zonal structures on mineral surfaces. Biogeochemistry 85:9–24
Kleber M, Eusterhues K, Keiluweit M, Mikutta C, Mikutta R, Nico PS (2015) Mineral-organic associations: formation, properties, and relevance in soil environments. Adv Agron 130:1–140
Koch BP, Dittmar T (2006) From mass to structure: an aromaticity index for high-resolution mass data of natural organic matter. Rapid Commun Mass Spectrom 20:926–932
LaCroix RE, Walpen N, Sander M, Tfaily MM, Blanchard JL, Keiluweit M (2021) Long-term warming decreases redox capacity of soil organic matter. Environ Sci Technol Lett 8:92–97
Lal K, Sehgal M, Gupta V, Sharma A, John O, Gummidi B, Jha V, Kumari A (2020) Assessment of groundwater quality of CKDu affected Uddanam region in Srikakulam district and across Andhra Pradesh. India Groundw Sustain Dev 11:100432
LaRowe DE, Van CP (2011) Degradation of natural organic matter: a thermodynamic analysis. Geochim Cosmochim Acta 75:2030–2042
Lechtenfeld OJ, Hertkorn N, Shen Y, Witt M, Benner R (2015) Marine sequestration of carbon in bacterial metabolites. Nat Commun 6:6711
Liu Y, Ye Q, Huang WL, Feng L, Wang YH, Xie Z, Yong SS, Zhang S, Jiang B, Zheng Y, Wang JJ (2020) Spectroscopic and molecular-level characteristics of dissolved organic matter in the Pearl River Estuary. South China Sci Total Environ 710:136307
Lu Q, He D, Pang Y, Zhang Y, He C, Wang Y, Zhang H, Shi Q, Sun Y (2020) Processing of dissolved organic matter from surface waters to sediment pore waters in a temperate coastal wetland. Sci Total Environ 742:140491
Makehelwala M, Wei Y, Weragoda S, Weerasooriya R, Zheng L (2019) Characterization of dissolved organic carbon in shallow groundwater of chronic kidney disease affected regions in Sri Lanka. Sci Total Environ 660:865–875
Makehelwala M, Wei Y, Weragoda SK, Weerasooriya R (2020) Ca2+ and SO42- interactions with dissolved organic matter: implications of groundwater quality for CKDu incidence in Sri Lanka. J Environ Sci 88:326–337
McDonough LK, Meredith KT, Nikagolla C, Middleton RJ, Tan JK, Ranasinghe AV, Sierro F, Banati RB (2020) The water chemistry and microbiome of household wells in Medawachchiya, Sri Lanka, an area with high prevalence of chronic kidney disease of unknown origin (CKDu). Sci Rep 10:18295
McDonough LK, Meredith KT, Nikagolla C, Banati RB (2021) The influence of water–rock interactions on household well water in an area of high prevalence chronic kidney disease of unknown aetiology (CKDu). npj Clean Water 4:1–9
Mostovaya A, Hawkes JA, Dittmar T, Tranvik LJ (2017) Molecular determinants of dissolved organic matter reactivity in lake water. Front Earth Sci 5:106
Ogawa H, Amagai Y, Koike I, Kaiser K, Benner R (2001) Production of refractory dissolved organic matter by bacteria. Science 292:917–920
Ojeda AS, Widener J, Aston CE, Philp RP (2018) ESRD and ESRD-DM associated with lignite-containing aquifers in the U.S. Gulf Coast region of Arkansas, Louisiana, and Texas. Int J Hyg Environ Health 221:958–966
Powers LC, Lapham LL, Malkin SY, Heyes A, Schmitt KP, Gonsior M (2021) Molecular and optical characterization reveals the preservation and sulfurization of chemically diverse porewater dissolved organic matter in oligohaline and brackish Chesapeake Bay sediments. Org Geochem 161:104324
Pracht LE, Tfaily MM, Ardissono RJ, Neumann RB (2018) Molecular characterization of organic matter mobilized from Bangladeshi aquifer sediment: tracking carbon compositional change during microbial utilization. Biogeosciences 15:1733–1747
Qi Y, Xie Q, Wang JJ, He D, Bao HY, Fu QL, Su SH, Sheng M, Li SL, Volmer DA, Wu FC, Jiang GB, Liu CQ, Fu PQ (2022) Deciphering dissolved organic matter by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS): from bulk to fractions and individuals. Carbon Res 1:3
Qiao W, Guo H, He C, Shi Q, Xiu W, Zhao B (2020) Molecular evidence of arsenic mobility linked to biodegradable organic matter. Environ Sci Technol 54:7280–7290
Qiao W, Guo H, He C, Shi Q, Xing S, Gao Z (2021a) Identification of processes mobilizing organic molecules and arsenic in geothermal confined groundwater from Pliocene aquifers. Water Res 198:117140
Qiao W, Guo H, He C, Shi Q, Zhao B (2021b) Unraveling roles of dissolved organic matter in high arsenic groundwater based on molecular and optical signatures. J Hazard Mater 406:124702
Santl-Temkiv T, Finster K, Dittmar T, Hansen BM, Thyrhaug R, Nielsen NW, Karlson UG (2013) Hailstones: a window into the microbial and chemical inventory of a storm cloud. PLoS ONE 8:e53550
Schmidt F, Koch BP, Elvert M, Schmidt G, Witt M, Hinrichs KU (2011) Diagenetic transformation of dissolved organic nitrogen compounds under contrasting sedimentary redox conditions in the Black Sea. Environ Sci Technol 45:5223–5229
Schmidt F, Koch BP, Goldhammer T, Elvert M, Witt M, Lin YS, Wendt J, Zabel M, Heuer VB, Hinrichs KU (2017) Unraveling signatures of biogeochemical processes and the depositional setting in the molecular composition of pore water DOM across different marine environments. Geochim Cosmochim Acta 207:57–80
Sivonen K (2019) Cyanobacterial toxins and toxin production. Phycologia 35:12–24
Spencer RGM, Mann PJ, Dittmar T, Eglinton TI, McIntyre C, Holmes RM, Zimov N, Stubbins A (2015) Detecting the signature of permafrost thaw in Arctic rivers. Geophys Res Lett 42:2830–2835
Sulaiman MM, Shettima J, Ndahi K, Abdul H, Mohammed MB, Ummate I, Hussein K (2018) Chronic kidney disease of unknown origin in Northern Yobe, Nigeria: experience from a regional tertiary hospital in northeastern Nigeria. Borno Med J 16:1–8
Sung JM, Chang WH, Liu KH, Chen CY, Mahmudiono T, Wang WR, Hsu HC, Li ZY, Chen HL (2022) The effect of co-exposure to glyphosate, cadmium, and arsenic on Chronic Kidney Disease. Expos Health
Udeshani WAC, Dissanayake HMKP, Gunatilake SK, Chandrajith R (2020) Assessment of groundwater quality using water quality index (WQI): a case study of a hard rock terrain in Sri Lanka. Groundw Sustain Dev 11:100421
Wang K, Li P, He C, Shi Q, He D (2021) Hydrologic heterogeneity induced variability of dissolved organic matter chemistry among tributaries of the Three Gorges Reservoir. Water Res 201:117358
Wickramarathna S, Balasooriya S, Diyabalanage S, Chandrajith R (2017) Tracing environmental aetiological factors of chronic kidney diseases in the dry zone of Sri Lanka—a hydrogeochemical and isotope approach. J Trace Elem Med Biol 44:298–306
Wimalawansa SJ (2015) Escalating chronic kidney diseases of multi-factorial origin (CKD-mfo) in Sri Lanka: causes, solutions, and recommendations-update and responses. Environ Health Prev Med 20:152–157
Wu T, Liu H (2003) Estimating the area under a receiver operating characteristic curve for repeated measures design. J Stat Softw 8:1548–7660
Wu CT, Wang CC, Huang LC, Liu SH, Chiang CK (2018) Plasticizer Di-(2-Ethylhexyl)Phthalate induces epithelial-to-mesenchymal transition and renal fibrosis in vitro and in vivo. Toxicol Sci 164:363–374
Xu W, Gao A, He C, Shi Q, Hou Z, Zhao HZ (2020) Using ESI FT-ICR MS to characterize dissolved organic matter in salt lakes with different salinity. Environ Sci Technol 54:12929–12937
Zeng XJ, He W, Guo HM, Shi QT, Zheng YX, Meththika V, Jin H (2022) Recognizing the groundwater related to chronic kidney disease of unknown etiology by humic-like organic matter. npj Clean Water 5:8
Zheng L, Cooray T, Zhong H, Weragoda S, Wei Y (2020) Critical challenges and solutions on ground drinking water in chronic kidney disease of unknown etiology (CKDu) affected regions in Sri Lanka. Chin J Environ Eng 14:2100–2111
Funding
The study was financially supported by the National Natural Science Foundation of China (Grant Nos. 41861144027, 41825017, and 42177201), 111 Project (No. B20010), and the Fundamental Research Funds for the Central Universities (No. 265QZ2021004). Sampling in Sri Lanka was supported by National Science Foundation Grant No. ICRP/NSF-NSFC/2019/BS/01.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. XZ: Data Curation, Laboratory testing, Writing- Original Draft. WH: Writing- Design, Writing- Reviewing and Editing, Funding acquisition. HG: Funding acquisition, Writing- Reviewing and Editing, Project administration, Resources, Supervision. CH: Laboratory testing. QS: Laboratory testing. QS: Laboratory testing. MV: Samples collection, Funding acquisition.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Ethical Approval
Not applicable.
Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Zeng, X., He, W., Guo, H. et al. Molecular Linkage of Dissolved Organic Matter in Groundwater with Prevalence of Chronic Kidney Disease with Unknown Etiology. Expo Health 15, 489–503 (2023). https://doi.org/10.1007/s12403-022-00509-w
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12403-022-00509-w