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

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  • Nanayakkara Shanika
    Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University Institute of Dental Research, Westmead Centre for Oral Health, Faculty of Dentistry, The University of Sydney
  • Senevirathna STMLD
    Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University School of Computing, Engineering and Mathematics, University of Western Sydney
  • Abeysekera Tilak
    Department of Pharmacology, Faculty of Medicine, University of Peradeniya
  • Chandrajith Rohana
    Department of Geology, Faculty of Science, University of Peradeniya
  • Ratnatunga Neelakanthi
    Department of Pathology, Faculty of Medicine, University of Peradeniya
  • Gunarathne EDL
    Girandurukotte Base Hospital
  • Yan Junxia
    Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University
  • Hitomi Toshiaki
    Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University
  • Muso Eri
    Department of Nephrology and Dialysis, Tazuke Kofukai Medical Research Institute, Kitano Hospital
  • Komiya Toshiyuki
    Department of Nephrology and Dialysis, Tazuke Kofukai Medical Research Institute, Kitano Hospital
  • Harada Kouji H.
    Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University
  • Liu Wanyang
    Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University
  • Kobayashi Hatasu
    Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University
  • Okuda Hiroko
    Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University
  • Sawatari Hideyuki
    Miyagi University of Education
  • Matsuda Fumihiko
    Center for Genomic Medicine, Graduate School of Medicine, Kyoto University
  • Yamada Ryo
    Center for Genomic Medicine, Graduate School of Medicine, Kyoto University
  • Watanabe Takao
    Miyagi University of Education
  • Miyataka Hideki
    Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
  • Himeno Seiichiro
    Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
  • Koizumi Akio
    Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University

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Objectives: Previous investigations on chronic kidney disease of unknown etiology characterized by tubulointerstitial damages (CKDu) in the North Central Region (NCR) of Sri Lanka have supported the involvement of social, environmental and genetic factors in its pathogenesis. Methods: We conducted a social-environmental-and-genetic epidemiology study on a male population in NCR to investigate the genetic and environmental contributors. We recruited 311 case-series patients and 504 control candidates. Of the 504 control candidates, 218 (43%) were eliminated because of the presence of hypertension, proteinuria, high HbA1c, high serum creatinine or high alpha-1 microglobulin in urine. Results and Discussion: None of 18 metals measured (μg//) in urine, including Cd, As and Pb, showed significantly higher concentrations in cases compared with controls. As speciation results showed that 75–80% of total urinary As was in the form of arsenobetaine, which is non-toxic to humans. None of the metal concentrations in drinking water samples exceeded guideline values. A genome-wide association study (GWAS) was conducted to determine the genetic contributors. The GWAS yielded a genome-wide significant association with CKDu for a single nucleotide polymorphism (SNP; rs6066043; p=5.23 × 10−9 in quantitative trait locus analysis; p=3.73 × 10−9 in dichotomous analysis) in SLC13A3 (sodium-dependent dicarboxylate transporter member 3). The population attributable fraction and odds ratio for this SNP were 50% and 2.13. Genetic susceptibility was identified as the major risk factor for CKDu. However, 43% of the apparently healthy malepopulation suffers from non-communicable diseases, suggesting their possible influence on CKDu progression.(J Occup Health 2014; 56: 28–38)

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