{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:10:00Z","timestamp":1792811400567,"version":"4.5.0"},"reference-count":212,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Chronic Kidney Disease of Unknown Etiology (CKDu) is a worldwide hidden health threat that is associated with progressive loss of kidney functions without showing any initial symptoms until reaching end-stage renal failure, eventually leading to death. It is a growing health problem in Asia, Central America, Africa, and the Middle East, with identified hotspots. CKDu disease mainly affects young men in rural farming communities, while its etiology is not related to hypertension, kidney stones, diabetes, or other known causes. The main suspected causal factors are heat-stress, dehydration, exposure to agrochemicals, heavy metals and use of hard water, infections, mycotoxins, nephrotoxic agents, altitude, and genetic factors. This review gives an overview of CKDu and sheds light on its medical history, geographic distribution, and worldwide prevalence. It also summarizes the suspected causal factors, their proposed mechanisms of action, as well as the main methods used in the CKDu prior detection and surveillance. In addition, mitigation measures to reduce the burden of CKDu are also discussed. Further investigation utilizing more robust study designs would provide a better understanding of the risk factors linked to CKDu and their comparison between affected regions.<\/jats:p>","DOI":"10.3390\/pathophysiology31040052","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T11:16:48Z","timestamp":1733743008000},"page":"761-786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Chronic Kidney Disease of Unknown Etiology: A Global Health Threat in Rural Agricultural Communities\u2014Prevalence, Suspected Causes, Mechanisms, and Prevention Strategies"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9516-3717","authenticated-orcid":false,"given":"Zineb","family":"Ben Khadda","sequence":"first","affiliation":[{"name":"Laboratory of Epidemiology and Research in Health Sciences, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, PO 1893, Km 2200, Route Sidi Harazem, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitam","family":"Lahmamsi","sequence":"additional","affiliation":[{"name":"Laboratory of Microbial Biotechnology and Bioactive Molecules, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, Route Immouzer BP 2202, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahya","family":"El Karmoudi","sequence":"additional","affiliation":[{"name":"Laboratory of Ecology, Systematics, Conservation of Biodiversity, LESCB URL-CNRST N\u00b0 18, Faculty of Sciences, Abdelmalek Essaadi University, PO 2121 M\u2019Hannech II, Tetouan 93002, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3227-0948","authenticated-orcid":false,"given":"Said","family":"Ezrari","sequence":"additional","affiliation":[{"name":"Microbiology Unit, Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Medicine and Pharmacy Oujda, Mohammed First University, PO 4867 Oujda University, Oujda 60049, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"El Hanafi","sequence":"additional","affiliation":[{"name":"Department of Biology, Laboratory of Functional Ecology and Engineering Environment, Sidi Mohamed Ben Abdellah University, Route Immouzer BP 2202, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-288X","authenticated-orcid":false,"given":"Tarik","family":"Sqalli Houssaini","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Research in Health Sciences, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, PO 1893, Km 2200, Route Sidi Harazem, Fez 30000, Morocco"},{"name":"Department of Nephrology, Hassan II University Hospital, BP 1835, Atlas, Road of Sidi Harazem, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0140-6736(13)60687-X","article-title":"Chronic kidney disease: Global dimension and perspectives","volume":"382","author":"Jha","year":"2013","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e307","DOI":"10.1016\/S2214-109X(16)00071-1","article-title":"Chronic kidney disease and cardiovascular risk in six regions of the world (ISN-KDDC): A cross-sectional study","volume":"4","author":"Perico","year":"2016","journal-title":"Lancet Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Redmon, J.H., Elledge, M.F., Womack, D.S., Wickremashinghe, R., Wanigasuriya, K.P., Peiris-John, R.J., Lunyera, J., Smith, K., Raymer, J.H., and Levine, K.E. (2014). Additional perspectives on chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka\u2014Lessons learned from the WHO CKDu population prevalence study. BMC Nephrol., 15.","DOI":"10.1186\/1471-2369-15-125"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1136\/postgradmedj-2012-201141rep","article-title":"An epidemic of chronic kidney disease in Central America: An overview","volume":"89","author":"McClean","year":"2013","journal-title":"Postgrad. Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1007\/s10653-019-00264-z","article-title":"Chronic kidney disease of unknown aetiology in Sri Lanka and the exposure to environmental chemicals: A review of literature","volume":"41","author":"Kulathunga","year":"2019","journal-title":"Environ. Geochem. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.semnephrol.2019.02.008","article-title":"Other Potential CKD Hotspots in the World: The Cases of Mexico and the United States","volume":"39","author":"Aguilar","year":"2019","journal-title":"Semin. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ekir.2016.11.003","article-title":"Endemic Nephropathy Around the World","volume":"2","author":"Gifford","year":"2016","journal-title":"Kidney Int. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.nephro.2018.07.303","article-title":"La n\u00e9phropathie m\u00e9so-am\u00e9ricaine: Une pathologie intertropicale mondiale? \u00c9tude pr\u00e9liminaire","volume":"14","author":"Dueymes","year":"2018","journal-title":"Nephrol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"848","DOI":"10.2471\/BLT.17.196758","article-title":"Uddanam nephropathy in India: A challenge for epidemiologists","volume":"95","author":"Gadde","year":"2017","journal-title":"Bull. World Health Organ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1016\/j.ekir.2021.08.011","article-title":"Seasonal Changes in Kidney Function in CKD of Uncertain Etiology","volume":"6","author":"Arora","year":"2021","journal-title":"Kidney Int. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1159\/000513014","article-title":"Chronic Kidney Disease of Undetermined Etiology around the World","volume":"46","author":"Floris","year":"2021","journal-title":"Kidney Blood Press. Res."},{"key":"ref_12","first-page":"38","article-title":"A comprehensive review of Chronic Kidney Disease of Unknown Etiology","volume":"3","author":"Fernando","year":"2018","journal-title":"Int. J. Sci. Tech. Res. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39","DOI":"10.37757\/MR2014.V16.N2.7","article-title":"Clinical characteristics of chronic kidney disease of nontraditional causes in Salvadoran farming communities","volume":"16","author":"Herrera","year":"2014","journal-title":"MEDICC Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2161-0525.1000542","article-title":"Is Glyphosate a Key Factor in Mesoamerican Nephropathy?","volume":"8","author":"Seneff","year":"2018","journal-title":"J. Environ. Anal. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.etp.2010.11.006","article-title":"Ochratoxin A levels in human serum and foods from nephropathy patients in Tunisia: Where are you now?","volume":"64","author":"Khlifa","year":"2012","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.nephro.2021.11.005","article-title":"Prevalence and risk factors associated with chronic kidney disease in Moroccan rural communes: Fez-Meknes region","volume":"18","author":"Berni","year":"2022","journal-title":"Nephrol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1080\/0886022X.2020.1824924","article-title":"Occupational risk factors for chronic kidney disease in Andhra Pradesh: \u2018Uddanam Nephropathy\u2019","volume":"42","author":"Farag","year":"2020","journal-title":"Ren. Fail."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.2215\/CJN.13841215","article-title":"Climate Change and the Emergent Epidemic of CKD from Heat Stress in Rural Communities: The Case for Heat Stress Nephropathy","volume":"11","author":"Glaser","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106019","DOI":"10.1016\/j.envint.2020.106019","article-title":"Kidney developmental effects of metal-herbicide mixtures: Implications for chronic kidney disease of unknown etiology","volume":"144","author":"Babich","year":"2020","journal-title":"Environ. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12940-017-0254-0","article-title":"Pesticide exposures and chronic kidney disease of unknown etiology: An epidemiologic review","volume":"16","author":"Valcke","year":"2017","journal-title":"Environ. Health"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Weaver, V.M., Fadrowski, J.J., and Jaar, B.G. (2015). Global dimensions of chronic kidney disease of unknown etiology (CKDu): A modern era environmental and\/or occupational nephropathy?. BMC Nephrol., 16.","DOI":"10.1186\/s12882-015-0105-6"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"591","DOI":"10.34067\/KID.0003172020","article-title":"Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? PRO","volume":"1","author":"Vervaet","year":"2020","journal-title":"Kidney360"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.37757\/MR2014.V16.N2.3","article-title":"Chronic kidney disease of unknown etiology in agricultural communities","volume":"16","author":"Almaguer","year":"2014","journal-title":"MEDICC Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1681\/ASN.20213210S1595b","article-title":"Dysmorphic Lysosomes, Pathognomonic of Chronic Interstitial Nephritis in Agricultural Communities (CINAC)","volume":"32","author":"Olano","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1056\/NEJMra1813869","article-title":"Chronic Kidney Disease of Unknown Cause in Agricultural Communities","volume":"380","author":"Johnson","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_26","first-page":"234","article-title":"Chronic interstitial nephritis in agricultural communities: A worldwide epidemic with social, occupational and environmental determinants","volume":"32","author":"Jayasumana","year":"2017","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.ekir.2022.02.019","article-title":"Chronic Interstitial Nephritis in Agricultural Communities: A Patient in Paraguay","volume":"7","author":"Vervaet","year":"2022","journal-title":"Kidney Int. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"110414","DOI":"10.1016\/j.mehy.2020.110414","article-title":"Chronic interstitial nephritis in agricultural communities (CINAC) and lysosomal tubulopathy: Is there a place for anti-oxidants?","volume":"146","author":"Rodrigo","year":"2021","journal-title":"Med. Hypotheses"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.kint.2019.10.005","article-title":"Uncovering the etiology of CINAC, a complex and mysterious renal syndrome: The invaluable role of histopathology and electron microscopy","volume":"97","author":"Haas","year":"2020","journal-title":"Kidney Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.kint.2019.11.009","article-title":"Chronic interstitial nephritis in agricultural communities is a toxin-induced proximal tubular nephropathy","volume":"97","author":"Vervaet","year":"2020","journal-title":"Kidney Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1053\/j.ajkd.2013.10.062","article-title":"CKD of Unknown Origin in Central America: The Case for a Mesoamerican Nephropathy","volume":"63","author":"Wesseling","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.nefro.2021.03.005","article-title":"Mesoamerican nephropathy: A not so unknown chronic kidney disease. Nefropat\u00eda end\u00e9mica mesoamericana: Una enfermedad renal cr\u00f3nica de origen no tan desconocido","volume":"41","author":"Serrano","year":"2021","journal-title":"Nefrologia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.semnephrol.2019.02.004","article-title":"Mesoamerican Nephropathy","volume":"39","year":"2019","journal-title":"Semin. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Courville, K., Bustamante, N., Hurtado, B., Pecchio, M., Rodr\u00edguez, C., N\u00fa\u00f1ez-Samudio, V., and Landires, I. (2022). Chronic kidney disease of nontraditional causes in central Panama. BMC Nephrol., 23.","DOI":"10.1186\/s12882-022-02907-3"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1111\/j.1523-1755.2005.09705.x","article-title":"Chronic kidney disease in Costa Rica","volume":"68","author":"Cerdas","year":"2005","journal-title":"Kidney Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.envres.2015.07.007","article-title":"Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador\u2014A cross-shift study of workers at risk of Mesoamerican nephropathy","volume":"142","author":"Wesseling","year":"2015","journal-title":"Environ. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s12403-019-00340-w","article-title":"Possible links between groundwater geochemistry and chronic kidney disease of unknown etiology (CKDu): An investigation from the Ginnoruwa region in Sri Lanka","volume":"12","author":"Balasooriya","year":"2019","journal-title":"Expo. Health"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.semnephrol.2019.02.005","article-title":"Chronic Kidney Disease of Unknown Etiology: Hotspots in India and Other Asian Countries","volume":"39","author":"Abraham","year":"2019","journal-title":"Semin. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.ekir.2018.10.006","article-title":"High Prevalence of CKD of Unknown Etiology in Uddanam, India","volume":"4","author":"Tatapudi","year":"2018","journal-title":"Kidney Int. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gunasekara, T., De Silva, P.M.C., Herath, C., Siribaddana, S., Siribaddana, N., Jayasumana, C., Jayasinghe, S., Cardenas-Gonzalez, M., and Jayasundara, N. (2020). The Utility of Novel Renal Biomarkers in Assessment of Chronic Kidney Disease of Unknown Etiology (CKDu): A Review. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17249522"},{"key":"ref_41","first-page":"e17132","article-title":"Chronic Kidney Disease of Unknown Origin: A Mysterious Epidemic","volume":"13","author":"Paidi","year":"2021","journal-title":"Cureus"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1016\/j.ekir.2020.08.032","article-title":"A Newly Recognized Endemic Region of CKD of Undetermined Etiology (CKDu) in South India\u2014\u201cTondaimandalam Nephropathy\u201d","volume":"5","author":"Parameswaran","year":"2020","journal-title":"Kidney Int. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1191\/0960327103ht328oa","article-title":"Ochratoxin A and human chronic nephropathy in Tunisia: Is the situation endemic?","volume":"22","author":"Abid","year":"2003","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.21608\/ejhm.2019.40003","article-title":"Epidemiology of End Stage Renal Disease Patients on Regular Hemodialysis in El-Beheira Governorate, Egypt","volume":"76","author":"Emam","year":"2019","journal-title":"Egypt. J. Hosp. Med."},{"key":"ref_45","first-page":"507","article-title":"Diabetics on hemodialysis in El-Minia Governorate, Upper Egypt: Five-year study","volume":"43","author":"Kamel","year":"2010","journal-title":"Int. Urol. Nephrol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4103\/jesnt.jesnt_10_17","article-title":"Maintenance hemodialysis in Menoufia governorate, Egypt: Is there any progress?","volume":"17","year":"2017","journal-title":"J. Egypt. Soc. Nephrol. Transplant."},{"key":"ref_47","first-page":"431","article-title":"Environmental Factors Incriminated in the Development of End Stage Renal Disease in El-Minia Governorate, Upper Egypt","volume":"2","author":"Kamel","year":"2010","journal-title":"Nephro-Urol Mon."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s12026-017-8901-7","article-title":"NLRP3 inflammasome activation regulated by NF-\u03baB and DAPK contributed to paraquat-induced acute kidney injury","volume":"65","author":"Liu","year":"2017","journal-title":"Immunol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1136\/oemed-2019-105772","article-title":"Environmental exposures in young adults with declining kidney function in a population at risk of Mesoamerican nephropathy","volume":"76","author":"Smpokou","year":"2019","journal-title":"Occup. Environ. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1080\/10807039.2021.1944050","article-title":"Pesticide-induced changes in cholinesterase activity and chronic kidney disease of unknown etiology among farmers in Nakhon Ratchasima, Thailand","volume":"27","author":"Sombatsawat","year":"2021","journal-title":"Hum. Ecol. Risk Assessment Int. J."},{"key":"ref_51","first-page":"e35","article-title":"Risk factors for chronic kidney disease of non-traditional causes: A systematic review","volume":"43","author":"Chapman","year":"2019","journal-title":"Rev. Panam. De Salud Publica-Pan Am. J. Public Health"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31","DOI":"10.37757\/MR2014.V16.N2.6","article-title":"Spatial Distribution of Unspecified Chronic Kidney Disease in El Salvador by Crop Area Cultivated and Ambient Temperature","volume":"16","author":"VanDervort","year":"2014","journal-title":"MEDICC Rev."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Rajapaksha, H., Pandithavidana, D.R., and Dahanayake, J.N. (2021). Demystifying Chronic Kidney Disease of Unknown Etiology (CKDu): Computational Interaction Analysis of Pesticides and Metabolites with Vital Renal Enzymes. Biomolecules, 11.","DOI":"10.3390\/biom11020261"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.3892\/mmr.2017.6389","article-title":"Kidney and heavy metals\u2014The role of environmental exposure","volume":"15","author":"Lentini","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Orr, S.E., and Bridges, C.C. (2017). Chronic Kidney Disease and Exposure to Nephrotoxic Metals. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18051039"},{"key":"ref_56","first-page":"64","article-title":"Possible link of Chronic arsenic toxicity with Chronic Kidney Disease of unknown etiology in Sri Lanka","volume":"3","author":"Channa","year":"2013","journal-title":"J. Nat. Sci. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Jayalal, T.B.A., Bandara, T.W.M.A.J., Mahawithanage, S.T.C., Wansapala, M.A.J., and Galappaththi, S.P.L. (2019). A quantitative analysis of chronic exposure of selected heavy metals in a model diet in a CKD hotspot in Sri Lanka. BMC Nephrol., 20.","DOI":"10.1186\/s12882-019-1371-5"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1476-069X-14-6","article-title":"Drinking well water and occupational exposure to Herbicides is associated with chronic kidney disease, in Padavi-Sripura, Sri Lanka","volume":"14","author":"Jayasumana","year":"2015","journal-title":"Environ. Health"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1007\/s10661-016-5524-8","article-title":"Quest to identify geochemical risk factors associated with chronic kidney disease of unknown etiology (CKDu) in an endemic region of Sri Lanka\u2014A multimedia laboratory analysis of biological, food, and environmental samples","volume":"188","author":"Levine","year":"2016","journal-title":"Environ. Monit. Assess."},{"key":"ref_60","first-page":"40","article-title":"Heavy metal contamination in surface sediments of major tanks in Anuradhapura district: A CKDu endemic district in Sri Lanka","volume":"41","author":"Perera","year":"2021","journal-title":"EQA\u2014Int. J. Environ. Qual."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1159\/000381239","article-title":"Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease","volume":"66","author":"Lanaspa","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e011034","DOI":"10.1136\/bmjopen-2016-011034","article-title":"Heat stress, hydration and uric acid: A cross-sectional study in workers of three occupations in a hotspot of Mesoamerican nephropathy in Nicaragua","volume":"6","author":"Wesseling","year":"2016","journal-title":"BMJ Open"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100928","DOI":"10.1016\/j.pmedr.2019.100928","article-title":"Relevance of heat stress and dehydration to chronic kidney disease (CKDu) in Sri Lanka","volume":"15","author":"Jayasekara","year":"2019","journal-title":"Prev. Med. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"146","DOI":"10.4103\/0971-4065.140712","article-title":"Dehydration and malaria augment the risk of developing chronic kidney disease in Sri Lanka","volume":"25","author":"Siriwardhana","year":"2015","journal-title":"Indian J. Nephrol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.3402\/gha.v2i0.2069","article-title":"Heat stress assessment among workers in a Nicaraguan sugarcane farm","volume":"2","author":"Cortez","year":"2009","journal-title":"Glob. Health Action"},{"key":"ref_66","first-page":"163","article-title":"Impact of climate change on occupational health and productivity: A systematic literature review focusing on workplace heat","volume":"109","author":"Levi","year":"2018","journal-title":"Med. Lav."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ekir.2017.10.006","article-title":"Kidney Diseases in Agricultural Communities: A Case Against Heat-Stress Nephropathy","volume":"3","author":"Herath","year":"2017","journal-title":"Kidney Int. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1539\/joh.13-0172-OA","article-title":"An Integrative Study of the Genetic, Social and Environmental Determinants of Chronic Kidney Disease Characterized by Tubulointerstitial Damages in the North Central Region of Sri Lanka","volume":"56","author":"Nanayakkara","year":"2014","journal-title":"J. Occup. Health"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jtemb.2017.08.013","article-title":"Tracing environmental aetiological factors of chronic kidney diseases in the dry zone of Sri Lanka\u2014A hydrogeochemical and isotope approach","volume":"44","author":"Wickramarathna","year":"2017","journal-title":"J. Trace Elements Med. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"197","DOI":"10.4038\/cjs.v48i3.7643","article-title":"Fluoride and hardness in groundwater of tropical regions\u2014Review of recent evidence indicating tissue calcification and calcium phosphate nanoparticle formation in kidney tubules","volume":"48","author":"Dissanayake","year":"2019","journal-title":"Ceylon J. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10653-015-9699-7","article-title":"Drinking water quality and chronic kidney disease of unknown etiology (CKDu): Synergic effects of fluoride, cadmium and hardness of water","volume":"38","author":"Wasana","year":"2015","journal-title":"Environ. Geochem. Health"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"140716","DOI":"10.1016\/j.scitotenv.2020.140716","article-title":"Evaluation of groundwater quality and reverse osmosis water treatment plants in the endemic areas of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka","volume":"745","author":"Imbulana","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Gobalarajah, K., Subramaniam, P., Jayawardena, U.A., Rasiah, G., Rajendra, S., and Prabagar, J. (2020). Impact of water quality on Chronic Kidney Disease of unknown etiology (CKDu) in Thunukkai Division in Mullaitivu District, Sri Lanka. BMC Nephrol., 21.","DOI":"10.1186\/s12882-020-02157-1"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.scitotenv.2010.10.046","article-title":"Dose-dependent Na and Ca in fluoride-rich drinking water \u2014Another major cause of chronic renal failure in tropical arid regions","volume":"409","author":"Chandrajith","year":"2011","journal-title":"Sci. Total. Environ."},{"key":"ref_75","unstructured":"Botheju, W.S.M., and Liyanage, S.A. (2019, January 30). The Role of Fluoride, Cadmium and Water Hardness in Drinking Water: A Critical Study of Potential Factors of Chronic Kidney Disease of Unknown Etiology (CKDu) in the Prevalence Area, Sri Lanka. Proceedings of the 20th International Postgraduate Conference (IPRC 2019), Colombo, Sri Lanka."},{"key":"ref_76","first-page":"705","article-title":"Chronic kidney disease of unknown etiology and the effect of multiple-ion interactions","volume":"40","year":"2017","journal-title":"Environ. Geochem. Health"},{"key":"ref_77","first-page":"192","article-title":"Effectiveness, safety, and acceptance of silver diamine fluoride therapy and its implications for dental hygiene practice: Position paper and statement from the Canadian Dental Hygienists Association","volume":"52","author":"Farmer","year":"2018","journal-title":"Can. J. Dent. Hyg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3109\/0886022X.2011.623496","article-title":"Occupational Silica Exposure and Chronic Kidney Disease","volume":"34","author":"Vupputuri","year":"2011","journal-title":"Ren. Fail."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.chemosphere.2017.02.155","article-title":"Deleterious role of trace elements\u2014Silica and lead in the development of chronic kidney disease","volume":"177","author":"Mascarenhas","year":"2017","journal-title":"Chemosphere"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00204-014-1405-5","article-title":"Effects of silica exposure on the cardiac and renal inflammatory and fibrotic response and the antagonistic role of interleukin-1 beta in C57BL\/6 mice","volume":"90","author":"Guo","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.2215\/CJN.11571017","article-title":"Nephrotoxicity and Chinese herbal medicine","volume":"13","author":"Yang","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Barbieri, M.A., Rottura, M., Cicala, G., Mandraffino, R., Marino, S., Irrera, N., Mannucci, C., Santoro, D., Squadrito, F., and Arcoraci, V. (2020). Chronic Kidney Disease Management in General Practice: A Focus on Inappropriate Drugs Prescriptions. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051346"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Chiu, H.-Y., Huang, H.-L., Li, C.-H., Chen, H.-A., Yeh, C.-L., Chiu, S.-H., Lin, W.-C., Cheng, Y.-P., Tsai, T.-F., and Ho, S.-Y. (2015). Increased Risk of Chronic Kidney Disease in Rheumatoid Arthritis Associated with Cardiovascular Complications\u2014A National Population-Based Cohort Study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136508"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1053\/j.ackd.2012.04.005","article-title":"Nephrotoxicity of Alternative Medicine Practice","volume":"19","author":"Luyckx","year":"2012","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1080\/0886022X.2019.1628780","article-title":"Acute toxic kidney injury","volume":"41","author":"Petejova","year":"2019","journal-title":"Ren. Fail."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.semnephrol.2017.02.005","article-title":"Traditional Medicines and Kidney Disease in Low- and Middle-Income Countries: Opportunities and Challenges","volume":"37","author":"Stanifer","year":"2017","journal-title":"Semin. Nephrol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/ki.2015.226","article-title":"Association of prescribed Chinese herbal medicine use with risk of end-stage renal disease in patients with chronic kidney disease","volume":"88","author":"Lin","year":"2015","journal-title":"Kidney Int."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.tox.2009.07.014","article-title":"Molecular evidence for an involvement of organic anion transporters (OATs) in aristolochic acid nephropathy","volume":"264","author":"Bakhiya","year":"2009","journal-title":"Toxicology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1007\/s10495-006-0289-0","article-title":"Effect of aristolochic acid on intracellular calcium concentration and its links with apoptosis in renal tubular cells","volume":"11","author":"Hsin","year":"2006","journal-title":"Apoptosis"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Yang, F., Ozols, E., Ma, F.Y., Leong, K.G., Tesch, G.H., Jiang, X., and Nikolic-Paterson, D.J. (2021). c-Jun Amino Terminal Kinase Signaling Promotes Aristolochic Acid-Induced Acute Kidney Injury. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.599114"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/sj.ki.5002714","article-title":"Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation","volume":"73","author":"Pozdzik","year":"2008","journal-title":"Kidney Int."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Baudoux, T., Jadot, I., Decl\u00e8ves, A.-E., Antoine, M.-H., Colet, J.-M., Botton, O., De Prez, E., Pozdzik, A., Husson, C., and Caron, N. (2022). Experimental Aristolochic Acid Nephropathy: A Relevant Model to Study AKI-to-CKD Transition. Front. Med., 9.","DOI":"10.3389\/fmed.2022.822870"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s12250-016-3899-x","article-title":"Hantavirus infection: A global zoonotic challenge","volume":"32","author":"Jiang","year":"2017","journal-title":"Virol. Sin."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S0953-6205(02)00037-7","article-title":"Acute renal failure caused by leptospirosis and Hantavirus infection in an urban hospital","volume":"13","author":"Sion","year":"2002","journal-title":"Eur. J. Intern. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000480691","article-title":"Leptospirosis Renal Disease: Emerging Culprit of Chronic Kidney Disease Unknown Etiology","volume":"138","author":"Yang","year":"2018","journal-title":"Nephron"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"D\u2019Andon, M.F., Quellard, N., Fernandez, B., Ratet, G., Lacroix-Lamand\u00e9, S., Vandewalle, A., Boneca, I.G., Goujon, J.-M., and Werts, C. (2014). Leptospira Interrogans Induces Fibrosis in the Mouse Kidney through Inos-Dependent, TLR- and NLR-Independent Signaling Pathways. PLoS Neglected Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002664"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1681\/ASN.2013070752","article-title":"Podocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice","volume":"25","author":"Veron","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Carrillo-Larco, R.M., Altez-Fernandez, C., Acevedo-Rodriguez, J.G., Ortiz-Acha, K., and Ugarte-Gil, C. (2019). Leptospirosis as a risk factor for chronic kidney disease: A systematic review of observational studies. PLoS Neglected Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007458"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Sarathkumara, Y.D., Gamage, C.D., Lokupathirage, S., Muthusinghe, D.S., Nanayakkara, N., Gunarathne, L., Shimizu, K., Tsuda, Y., Arikawa, J., and Yoshimatsu, K. (2019). Exposure to Hantavirus is a Risk Factor Associated with Kidney Diseases in Sri Lanka: A Cross Sectional Study. Viruses, 11.","DOI":"10.3390\/v11080700"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00705-018-4053-x","article-title":"Thailand orthohantavirus infection in patients with chronic kidney disease of unknown aetiology in Sri Lanka","volume":"164","author":"Yoshimatsu","year":"2018","journal-title":"Arch. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.mehy.2016.04.009","article-title":"Chronic kidney disease of uncertain etiology in Sri Lanka: Are leptospirosis and Hantaviral infection likely causes?","volume":"91","author":"Gamage","year":"2016","journal-title":"Med. Hypotheses"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1093\/ckj\/sfab136","article-title":"Aguascalientes: One of the hottest chronic kidney disease (CKD) hotspots in Mexico and a CKD of unknown aetiology mystery to be solved","volume":"14","author":"Villalvazo","year":"2021","journal-title":"Clin. Kidney J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1053\/j.ajkd.2011.11.039","article-title":"Decreased Kidney Function Among Agricultural Workers in El Salvador","volume":"59","author":"Peraza","year":"2012","journal-title":"Am. J. Kidney Dis."},{"key":"ref_104","first-page":"496","article-title":"What do epidemiological studies tell us about chronic kidney disease of undetermined cause in Meso-America? A systematic review and meta-analysis","volume":"11","author":"Pearce","year":"2017","journal-title":"Clin. Kidney, J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1681\/ASN.2010121316","article-title":"High Altitude Renal Syndrome (HARS)","volume":"22","author":"Arestegui","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"iv11","DOI":"10.1093\/ndt\/gfs427","article-title":"Cardiovascular and renal effects of chronic exposure to high altitude","volume":"27","author":"Hurtado","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Fitria, L., Prihartono, N.A., Ramdhan, D.H., Wahyono, T.Y.M., Kongtip, P., and Woskie, S. (2020). Environmental and Occupational Risk Factors Associated with Chronic Kidney Disease of Unknown Etiology in West Javanese Rice Farmers, Indonesia. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17124521"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"110270","DOI":"10.1016\/j.envres.2020.110270","article-title":"A comparative review: Chronic Kidney Disease of unknown etiology (CKDu) research conducted in Latin America versus Asia","volume":"192","author":"Redmon","year":"2020","journal-title":"Environ. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00128-011-0301-4","article-title":"Mycotoxin Detection in Urine Samples from Patients with Chronic Kidney Disease of Uncertain Etiology in Sri Lanka","volume":"87","author":"Desalegn","year":"2011","journal-title":"Bull. Environ. Contam. Toxicol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1292\/jvms.16-0226","article-title":"Serum levels of ochratoxin A in dogs with chronic kidney disease (CKD): A retrospective study","volume":"79","author":"Meucci","year":"2017","journal-title":"J. Vet. Med. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1681\/ASN.2016010027","article-title":"Social Determinants of Racial Disparities in CKD","volume":"27","author":"Norton","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2215\/CJN.07500715","article-title":"CKD of Uncertain Etiology: A Systematic Review","volume":"11","author":"Lunyera","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1007\/s12199-015-0475-1","article-title":"Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka","volume":"20","author":"Nanayakkara","year":"2015","journal-title":"Environ. Health Prev. Med."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Ma, J., Yang, Q., Hwang, S.-J., Fox, C.S., and Chu, A.Y. (2017). Genetic risk score and risk of stage 3 chronic kidney disease. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0439-3"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.ekir.2017.08.012","article-title":"Occupational Heat Stress and Kidney Health: From Farms to Factories","volume":"2","author":"Nerbass","year":"2017","journal-title":"Kidney Int. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/ki.2013.492","article-title":"Fructokinase activity mediates dehydration-induced renal injury","volume":"86","author":"Jimenez","year":"2014","journal-title":"Kidney Int."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Hansson, E., Glaser, J., Jakobsson, K., Weiss, I., Wesseling, C., Lucas, R.A.I., Wei, J.L.K., Ekstr\u00f6m, U., Wijkstr\u00f6m, J., and Bodin, T. (2020). Pathophysiological Mechanisms by which Heat Stress Potentially Induces Kidney Inflammation and Chronic Kidney Disease in Sugarcane Workers. Nutrients, 12.","DOI":"10.3390\/nu12061639"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Akbarian, A., Michiels, J., DeGroote, J., Majdeddin, M., Golian, A., and De Smet, S. (2016). Association between heat stress and oxidative stress in poultry; mitochondrial dysfunction and dietary interventions with phytochemicals. J. Anim. Sci. Biotechnol., 7.","DOI":"10.1186\/s40104-016-0097-5"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jtherbio.2007.06.002","article-title":"Hyperthermia causes bovine mammary epithelial cell death by a mitochondrial-induced pathway","volume":"33","author":"Du","year":"2007","journal-title":"J. Therm. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.freeradbiomed.2005.10.064","article-title":"Mechanism of cell death induction by nitroxide and hyperthermia","volume":"40","author":"Zhao","year":"2006","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Zhai, R., Dong, X., Feng, L., Li, S., and Hu, Z. (2019). The Effect of Heat Stress on Autophagy and Apoptosis of Rumen, Abomasum, Duodenum, Liver and Kidney Cells in Calves. Animals, 9.","DOI":"10.3390\/ani9100854"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Brustovetsky, N. (2020). The Role of Adenine Nucleotide Translocase in the Mitochondrial Permeability Transition. Cells, 9.","DOI":"10.3390\/cells9122686"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"R812","DOI":"10.1152\/ajpregu.90708.2008","article-title":"Aging augments mitochondrial susceptibility to heat stress","volume":"296","author":"Haak","year":"2009","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_124","first-page":"119","article-title":"The stress response of the endoplasmic reticulum in the pathophysiology of chronic liver diseases","volume":"36","author":"Blanc","year":"2020","journal-title":"M\/S-Med. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3109\/02656736.2014.971446","article-title":"Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review","volume":"30","author":"Najar","year":"2014","journal-title":"Int. J. Hyperth."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1021\/tx200156k","article-title":"Mitochondria are the main target organelle for trivalent monomethylarsonous acid (MMAIII)-induced cytotoxicity","volume":"24","author":"Naranmandura","year":"2011","journal-title":"Chem. Res. Toxicol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1124\/pr.110.002980","article-title":"NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair","volume":"63","author":"Jiang","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Sharma, S., Gill, A.S., Singh, Z., Kaur, C., and Vijaya, P. (2016). Nephrotoxic Effects of Arsenic in Albino Mice. Am. J. Biosci., 4.","DOI":"10.11648\/j.ajbio.s.2016040301.11"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"8276","DOI":"10.1111\/jcmm.15301","article-title":"Lysosomal dysfunction\u2013induced autophagic stress in diabetic kidney disease","volume":"24","author":"Zheng","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.tibs.2013.12.001","article-title":"At the end of the autophagic road: An emerging understanding of lysosomal functions in autophagy","volume":"39","author":"Shen","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1111\/tra.12613","article-title":"Lysosomal membrane permeabilization and cell death","volume":"19","author":"Wang","year":"2018","journal-title":"Traffic"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"117148","DOI":"10.1016\/j.lfs.2019.117148","article-title":"High glucose augments ROS generation regulates mitochondrial dysfunction and apoptosis via stress signalling cascades in keratinocytes","volume":"241","author":"Rizwan","year":"2020","journal-title":"Life Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.toxrep.2022.01.002","article-title":"The preferential accumulation of cadmium ions among various tissues in mice","volume":"9","author":"Tai","year":"2022","journal-title":"Toxicol. Rep."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.tox.2017.03.016","article-title":"Cadmium disrupts autophagic flux by inhibiting cytosolic Ca 2+ -dependent autophagosome-lysosome fusion in primary rat proximal tubular cells","volume":"383","author":"Liu","year":"2017","journal-title":"Toxicology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.kint.2015.11.021","article-title":"Autophagy in acute kidney injury","volume":"89","author":"Kaushal","year":"2016","journal-title":"Kidney Int."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41580-018-0003-4","article-title":"Mechanism and medical implications of mammalian autophagy","volume":"19","author":"Dikic","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.chemosphere.2018.10.019","article-title":"Cadmium-mediated miR-30a-GRP78 leads to JNK-dependent autophagy in chicken kidney","volume":"215","author":"Shi","year":"2019","journal-title":"Chemosphere"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.tox.2015.11.005","article-title":"Exaggerated arsenic nephrotoxicity in female mice through estrogen-dependent impairments in the autophagic flux","volume":"339","author":"Kimura","year":"2016","journal-title":"Toxicology"},{"key":"ref_139","first-page":"821","article-title":"Protective effect of pomegranate seed oil against acute toxicity of diazinon in rat kidney","volume":"12","author":"Boroushaki","year":"2013","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"ref_140","first-page":"1","article-title":"Physiological and Histopathological Investigations on the Effects of-Lipoic Acid in Rats Exposed to Malathion","volume":"2010","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.etap.2006.09.003","article-title":"Oxidative stress after acute and sub-chronic malathion intoxication in Wistar rats","volume":"23","author":"Possamai","year":"2006","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1080\/08860220500200536","article-title":"Ultrastructural Effects of Acute Organophosphate Poisoning on Rat Kidney","volume":"27","author":"Satar","year":"2005","journal-title":"Ren. Fail."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.etp.2014.01.007","article-title":"Effect of quercetin against dichlorvos induced nephrotoxicity in rats","volume":"66","author":"Hou","year":"2014","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.pestbp.2010.04.006","article-title":"Chlorpyrifos-induced oxidative stress and histological changes in retinas and kidney in rats: Protective role of ascorbic acid and alpha tocopherol","volume":"98","author":"Ahmed","year":"2010","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.pestbp.2010.07.006","article-title":"Role of oxidative stress in organophosphate insecticide toxicity\u2014Short review","volume":"98","year":"2010","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"17007","DOI":"10.1038\/cddiscovery.2017.7","article-title":"Malathion increases apoptotic cell death by inducing lysosomal membrane permeabilization in N2a neuroblastoma cells: A model for neurodegeneration in Alzheimer\u2019s disease","volume":"3","author":"Venkatesan","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"108508","DOI":"10.1016\/j.fsi.2022.108508","article-title":"Crosstalk of oxidative stress, inflammation, apoptosis, and autophagy under reactive oxygen stress involved in difenoconazole-induced kidney damage in carp","volume":"132","author":"Wu","year":"2022","journal-title":"Fish Shellfish. Immunol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"113500","DOI":"10.1016\/j.ecoenv.2022.113500","article-title":"Impaired V-ATPase leads to increased lysosomal pH, results in disrupted lysosomal degradation and autophagic flux blockage, contributes to fluoride-induced developmental neurotoxicity","volume":"236","author":"Han","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"F387","DOI":"10.1152\/ajprenal.00285.2022","article-title":"The urinary proteome infers dysregulation of mitochondrial, lysosomal, and protein reabsorption processes in chronic kidney disease of unknown etiology (CKDu)","volume":"324","author":"Kolli","year":"2023","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_150","first-page":"13","article-title":"The protective effect of orange juice on Glyphosate toxicity in adult male mice","volume":"8","author":"Eman","year":"2016","journal-title":"J. Chem. Pharm. Res."},{"key":"ref_151","first-page":"403","article-title":"Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: Protective effect of selenium","volume":"57","year":"2008","journal-title":"Physiol. Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2016.06.001","article-title":"Mechanism-specific injury biomarkers predict nephrotoxicity early following glyphosate surfactant herbicide (GPSH) poisoning","volume":"258","author":"Mohamed","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e2251","DOI":"10.1038\/cddis.2016.78","article-title":"Endoplasmic reticulum stress eIF2\u03b1\u2013ATF4 pathway-mediated cyclooxygenase-2 induction regulates cadmium-induced autophagy in kidney","volume":"7","author":"Luo","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"260","DOI":"10.12688\/f1000research.13426.1","article-title":"NFAT control of immune function: New Frontiers for an Abiding Trooper","volume":"7","author":"Vaeth","year":"2018","journal-title":"F1000Research"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"13367","DOI":"10.1074\/jbc.273.22.13367","article-title":"Regulation of the Calmodulin-stimulated Protein Phosphatase, Calcineurin","volume":"273","author":"Klee","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Park, Y.-J., Yoo, S.-A., Kim, M., and Kim, W.-U. (2020). The Role of Calcium\u2013Calcineurin\u2013NFAT Signaling Pathway in Health and Autoimmune Diseases. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00195"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ceca.2017.01.014","article-title":"Calcium\u2013NFAT transcriptional signalling in T cell activation and T cell exhaustion","volume":"63","author":"Hogan","year":"2017","journal-title":"Cell Calcium"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"6754","DOI":"10.1021\/bi5009744","article-title":"Oxidation-Induced Conformational Changes in Calcineurin Determined by Covalent Labeling and Tandem Mass Spectrometry","volume":"53","author":"Zhou","year":"2014","journal-title":"Biochemistry"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Karolin, A., Escher, G., Rudloff, S., and Sidler, D. (2022). Nephrotoxicity of Calcineurin Inhibitors in Kidney Epithelial Cells is Independent of NFAT Signaling. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.789080"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Kaneko, S., Usui, J., Takahashi, K., Kimura, T., Hoshi, A., Nishiyama, H., Oda, T., and Yamagata, K. (2020). P0002A NEW INSIGHT INTO THE MECHANISM OF HYPERCHLOREMIC METABOLIC ACIDOSIS IN KIDNEY TRANSPLANT RECIPIENTS: INCREASED POSTGLOMERULAR PERITUBULAR BLOOD FLOW IS A KEY CONDITION FOR THE DEVELOPEMENT OF CALCINEURIN INHIBITOR-INDUCED RENAL TUBULAR ACIDOSIS. Nephrol. Dial. Transplant., 35.","DOI":"10.1093\/ndt\/gfaa142.P0002"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/0006-2952(92)90710-Z","article-title":"Specific inhibition of calcineurin by type II synthetic pyrethroid insecticides","volume":"43","author":"Enan","year":"1992","journal-title":"Biochem. Pharmacol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Schreurs, G., Maudsley, S., Nast, C., Praet, M., Fernandes, S.D.S., Boor, P., D\u2019haese, P., De Broe, M.E., and Vervaet, B.A. (2023). Chronic dehydration induces injury pathways in rats, but does not mimic histopathology of chronic interstitial nephritis in agricultural communities. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-43567-z"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.3390\/ijerph110202125","article-title":"Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka?","volume":"11","author":"Jayasumana","year":"2014","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_164","first-page":"56","article-title":"Clinical characteristics of chronic kidney disease of non-traditional causes in women of agricultural communities in El Salvador","volume":"83","author":"Orantes","year":"2015","journal-title":"Clin. Nephrol."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Sayanthooran, S., Magana-Arachchi, D.N., Gunerathne, L., and Abeysekara, T. (2017). Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: A pilot study. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0440-x"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.trsl.2012.01.020","article-title":"Genomic biomarkers for chronic kidney disease","volume":"159","author":"Ju","year":"2012","journal-title":"Transl. Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/ki.2011.198","article-title":"Biomarkers in chronic kidney disease: A review","volume":"80","author":"Fassett","year":"2011","journal-title":"Kidney Int."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrneph.2014.247","article-title":"Proteomic biomarkers in kidney disease: Issues in development and implementation","volume":"11","author":"Mischak","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12953-019-0155-y","article-title":"Chronic kidney disease: A review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers","volume":"17","author":"Taherkhani","year":"2019","journal-title":"Proteome Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1002\/prca.200700035","article-title":"Recent progress in urinary proteomics","volume":"1","author":"Thongboonkerd","year":"2007","journal-title":"Proteom.\u2014Clin. Appl."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Sirolli, V., Pieroni, L., Di Liberato, L., Urbani, A., and Bonomini, M. (2019). Urinary Peptidomic Biomarkers in Kidney Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010096"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1074\/mcp.M110.001917","article-title":"Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease","volume":"9","author":"Good","year":"2010","journal-title":"Mol. Cell. Proteom."},{"key":"ref_173","first-page":"93","article-title":"Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease","volume":"193","author":"Anderson","year":"2018","journal-title":"J. Proteom."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1172\/JCI72267","article-title":"Cellular and molecular mechanisms in kidney fibrosis","volume":"124","author":"Duffield","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/ki.2013.374","article-title":"ADQI 10 workgroup Potential use of biomarkers in acute kidney injury: Report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference","volume":"85","author":"Murray","year":"2014","journal-title":"Kidney Int."},{"key":"ref_176","first-page":"293","article-title":"Kidney injury molecule-1: A translational journey","volume":"125","author":"Bonventre","year":"2014","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1042\/CS20171592","article-title":"More than a simple biomarker: The role of NGAL in cardiovascular and renal diseases","volume":"132","author":"Buonafine","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.amjhyper.2007.01.010","article-title":"\u03b1-1 Microglobulin as a New Inflammatory Marker in Newly Diagnosed Hypertensive Patients","volume":"20","author":"Vyssoulis","year":"2007","journal-title":"Am. J. Hypertens."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Kristiansson, A., Gram, M., Flygare, J., Hansson, S.R., \u00c5kerstr\u00f6m, B., and Storry, J.R. (2020). The Role of \u03b11-Microglobulin (A1M) in Erythropoiesis and Erythrocyte Homeostasis\u2014Therapeutic Opportunities in Hemolytic Conditions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197234"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1001\/archinternmed.2007.64","article-title":"\u03b22-Microglobulin for Risk Stratification of Total Mortality in the Elderly PopulationComparison with Cystatin C and C-Reactive Protein","volume":"168","author":"Shinkai","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1158\/1055-9965.EPI-15-0849","article-title":"Circulating Beta-2 Microglobulin and Risk of Cancer: The Atherosclerosis Risk in Communities Study (ARIC)","volume":"25","author":"Prizment","year":"2016","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"e23748","DOI":"10.1002\/jcla.23748","article-title":"Distribution of urinary N-acetyl-beta-D-glucosaminidase and the establishment of reference intervals in healthy adults","volume":"35","author":"Liu","year":"2021","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"231","DOI":"10.21608\/ejhm.2021.142879","article-title":"Study of Urinary N-Acetyl-Beta-D-Glucosaminidase as a biomarker of Diabetic Nephropathy","volume":"82","author":"Mahmoud","year":"2021","journal-title":"Egypt. J. Hosp. Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"612","DOI":"10.2174\/1389203718666170918155247","article-title":"Regulation of Clusterin Gene Expression","volume":"19","author":"Serrano","year":"2018","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/14728222.2017.1267142","article-title":"Clusterin as a therapeutic target","volume":"21","author":"Wilson","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.clinbiochem.2018.07.003","article-title":"The multiple functions and mechanisms of osteopontin","volume":"59","author":"Icer","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1046\/j.1523-1755.2001.00032.x","article-title":"Expression, roles, receptors, and regulation of osteopontin in the kidney","volume":"60","author":"Xie","year":"2001","journal-title":"Kidney Int."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/2852398","article-title":"Tubulointerstitial Biomarkers for Diabetic Nephropathy","volume":"2018","author":"Satirapoj","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1089\/jir.2017.0140","article-title":"Increased Serum MCP-1 Levels in Systemic Vasculitis Patients with Renal Involvement","volume":"38","author":"Li","year":"2018","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"De Silva, P.M.C.S., Abdul, K.S.M., Eakanayake, E.M.D.V., Jayasinghe, S.S., Jayasumana, C., Asanthi, H.B., Perera, H.S.D., Chaminda, G.G.T., Chandana, E.P.S., and Siribaddana, S.H. (2016). Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka. PLoS Neglected Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004979"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.ekir.2019.07.009","article-title":"Pilot Study of Renal Urinary Biomarkers for Diagnosis of CKD of Uncertain Etiology","volume":"4","author":"Fernando","year":"2019","journal-title":"Kidney Int. Rep."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"15","DOI":"10.37757\/MR2016.V18.N1-2.4","article-title":"Chronic Kidney Disease in Children and Adolescents in Salvadoran Farming Communities: NefroSalva Pediatric Study (2009\u20132011)","volume":"18","author":"Morales","year":"2016","journal-title":"MEDICC Rev."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00467-020-04596-2","article-title":"CKDu: The known unknowns","volume":"36","author":"Abeyagunawardena","year":"2020","journal-title":"Pediatr. Nephrol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.kint.2022.03.019","article-title":"Genetics in chronic kidney disease: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference","volume":"101","author":"Gall","year":"2022","journal-title":"Kidney Int."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1056\/NEJMoa1806891","article-title":"Diagnostic Utility of Exome Sequencing for Kidney Disease","volume":"380","author":"Groopman","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Ahn, Y.H., Lee, C., Kim, N.K.D., Park, E., Kang, H.G., Ha, I.-S., Park, W.-Y., and Cheong, H.I. (2020). Targeted Exome Sequencing Provided Comprehensive Genetic Diagnosis of Congenital Anomalies of the Kidney and Urinary Tract. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030751"},{"key":"ref_197","first-page":"234","article-title":"Les grandes avanc\u00e9es en n\u00e9phro-g\u00e9n\u00e9tique p\u00e9diatrique [Major advances in pediatric nephro-genetics]","volume":"39","author":"Hureaux","year":"2023","journal-title":"Med. Sci."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1056\/NEJMsr1406261","article-title":"ClinGen\u2014The Clinical Genome Resource","volume":"372","author":"Rehm","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Moreno, J.A., Hamza, E., Guerrero-Hue, M., Rayego-Mateos, S., Garc\u00eda-Caballero, C., Vallejo-Mudarra, M., Metzinger, L., and Meuth, V.M.-L. (2021). Non-Coding RNAs in Kidney Diseases: The Long and Short of Them. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116077"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"e25086","DOI":"10.1002\/jcla.25086","article-title":"A Study on Associations of Long Noncoding RNA HOTAIR Polymorphisms With Genetic Susceptibility to Chronic Kidney Disease","volume":"38","author":"Majidpour","year":"2024","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cca.2018.09.011","article-title":"Urinary kidney injury molecule-1 in renal disease","volume":"487","author":"Moresco","year":"2018","journal-title":"Clin. Chim. Acta"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10653-010-9339-1","article-title":"Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: Geographic distribution and environmental implications","volume":"33","author":"Chandrajith","year":"2010","journal-title":"Environ. Geochem. Health"},{"key":"ref_203","first-page":"1","article-title":"Tackling the Fallout From Chronic Kidney Disease of Unknown Etiology: Why We Need to Focus on Providing Peritoneal Dialysis in Rural, Low-Resource Settings","volume":"2","author":"Nanayakkara","year":"2016","journal-title":"Kidney Int. Rep."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2054-3581-1-14","article-title":"Cost Analysis of In-Centre Nocturnal Compared with Conventional Hemodialysis","volume":"1","author":"Wong","year":"2014","journal-title":"Can. J. Kidney Health Dis."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"261","DOI":"10.4103\/ijn.IJN_396_19","article-title":"Options of renal replacement therapy in CKDu","volume":"30","author":"Varughese","year":"2020","journal-title":"Indian, J. Nephrol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2147\/IJNRD.S270709","article-title":"Mesoamerican Nephropathy (MeN): What We Know so Far","volume":"13","author":"Polo","year":"2020","journal-title":"Int. J. Nephrol. Renov. Dis."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"F726","DOI":"10.1152\/ajprenal.00543.2017","article-title":"Experimental heat stress nephropathy and liver injury are improved by allopurinol","volume":"315","author":"Sato","year":"2018","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1161\/01.HYP.17.2.194","article-title":"Nephrotoxicity of allopurinol is enhanced in experimental hypertension","volume":"17","author":"Trachtman","year":"1991","journal-title":"Hypertension"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/MNH.0000000000000491","article-title":"Clinical evidence that treatment of metabolic acidosis slows the progression of chronic kidney disease","volume":"28","author":"Goraya","year":"2019","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1159\/000494663","article-title":"Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate","volume":"48","author":"Gonzaga","year":"2018","journal-title":"Am. J. Nephrol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/S1957-2557(18)30093-2","article-title":"La metformine dans l\u2019insuffisance r\u00e9nale: Place (enfin) aux faits","volume":"12","author":"Lalau","year":"2018","journal-title":"M\u00e9decine Mal. M\u00e9taboliques"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jcjd.2018.04.004","article-title":"Safe Use of Metformin in Adults With Type 2 Diabetes and Chronic Kidney Disease: Lower Dosages and Sick-Day Education Are Essential","volume":"43","author":"MacCallum","year":"2018","journal-title":"Can. J. Diabetes"}],"container-title":["Pathophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1873-149X\/31\/4\/52\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:50:31Z","timestamp":1760115031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1873-149X\/31\/4\/52"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,9]]},"references-count":212,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["pathophysiology31040052"],"URL":"https:\/\/doi.org\/10.3390\/pathophysiology31040052","relation":{},"ISSN":["1873-149X"],"issn-type":[{"value":"1873-149X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,9]]}}}