title: Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka.
abstract: Chronic Kidney Disease of uncertain etiology (CKDu) is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are widely recognised for their sensitivity, specificity and accuracy in determining CKDu and early renal injury. However, these biomarkers have never been used in diagnosing CKDu in Sri Lanka. Male farmers (n = 1734) were recruited from 4 regions in Sri Lanka i.e. Matara and Nuwara Eliya (farming locations with no CKDu prevalence) and two CKDu emerging locations from Hambantota District in Southern Sri Lanka; Angunakolapelessa (EL1) and Bandagiriya (EL2). Albuminuria (ACR ≥ 30mg/g); serum creatinine based estimation of glomerular filtration rate (eGFR); creatinine normalized urinary kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured. Fourteen new CKDu cases (18%) from EL1 and nine CKDu cases (9%) from EL2 were recognized for the first time from EL1, EL2 locations, which were previously considered as non-endemic of the disease and associated with persistent albuminuria (ACR ≥ 30mg/g Cr). No CKDu cases were identified in non-endemic study locations in Matara (CM) and Nuwara Eliya (CN). Analysis of urinary biomarkers showed urinary KIM-1 and NGAL were significantly higher in new CKDu cases in EL1 and EL2. However, we also reported significantly higher KIM-1 and NGAL in apparently healthy farmers in EL 1 and EL 2 with comparison to both control groups. These observations may indicate possible early renal damage in absence of persistent albuminuria and potential capabilities of urinary KIM-1 and NGAL in early detection of renal injury among farming communities in Southern Sri Lanka.
authors.affiliation: Department of Zoology, Faculty of Science, University of Ruhuna, Matara, Sri Lanka.
authors.forename: Pallagae Mangala C S
authors.identifier: 0000-0002-1927-6512
authors.initials: PM
authors.lastname: De Silva
authors.affiliation: Department of Zoology, Faculty of Science, University of Ruhuna, Matara, Sri Lanka.
authors.forename: Khaja Shameem
authors.initials: KS
authors.lastname: Mohammed Abdul
authors.affiliation: Department of Zoology, Faculty of Science, University of Ruhuna, Matara, Sri Lanka.
authors.forename: Eakanayake M D V
authors.initials: EM
authors.lastname: Eakanayake
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka.
authors.forename: Sudheera Sammanthi
authors.initials: SS
authors.lastname: Jayasinghe
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Allied Sciences, Rajarata University, Saliyapura, Sri Lanka.
authors.forename: Channa
authors.initials: C
authors.lastname: Jayasumana
authors.affiliation: Department of Limnology, Faculty of Fisheries & Marine Sciences and Technology, University of Ruhuna, Matara, Sri Lanka.
authors.forename: Hewa Bandulage
authors.initials: HB
authors.lastname: Asanthi
authors.affiliation: Department of Limnology, Faculty of Fisheries & Marine Sciences and Technology, University of Ruhuna, Matara, Sri Lanka.
authors.forename: Hettiarachigae S D
authors.initials: HS
authors.lastname: Perera
authors.affiliation: Department of Civil Engineering, Faculty of Engineering, University of Ruhuna, Hapugala, Sri Lanka.
authors.forename: Gamage G Tushara
authors.initials: GG
authors.lastname: Chaminda
authors.affiliation: Department of Zoology, Faculty of Science, University of Ruhuna, Matara, Sri Lanka.
authors.forename: Ediriweera P S
authors.initials: EP
authors.lastname: Chandana
authors.affiliation: Department of Medicine, Faculty of Medicine and Allied Sciences, Rajarata University, Saliyapura, Sri Lanka.
authors.forename: Sisira H
authors.initials: SH
authors.lastname: Siribaddana
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000097:blood* / Q000652:urine*; D003430:Cross-Sectional Studies; D000067565:Farmers; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000032:analysis*; D006801:Humans; D016014:Linear Models; D000071068:Lipocalin-2 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000453:epidemiology*; D012307:Risk Factors; D013188:Sri Lanka / Q000453:epidemiology; D035501:Uncertainty
chemical_list: D015415:Biomarkers; D003404:Creatinine; D006442:Glycated Hemoglobin; D000072596:Hepatitis A Virus Cellular Receptor 1; D000071068:Lipocalin-2; C491143:HAVCR1 protein, human; C489506:LCN2 protein, human; C517652:hemoglobin A1c protein, human