Environmental Health and Preventive Medicine

, Volume 17, Issue 2, pp 109–117

Evidence of tubular damage in the very early stage of chronic kidney disease of uncertain etiology in the North Central Province of Sri Lanka: a cross-sectional study

  • Shanika Nanayakkara
  • S. T. M. L. D. Senevirathna
  • Upul Karunaratne
  • Rohana Chandrajith
  • Kouji H. Harada
  • Toshiaki Hitomi
  • Takao Watanabe
  • Tilak Abeysekera
  • T. N. C. Aturaliya
  • Akio Koizumi
Regular Article



In the North Central Province of Sri Lanka, chronic kidney disease of uncertain etiology (CKDue) has increased markedly over the past 15–20 years.


From around 4,700 patients who were followed up, 106 affected patients who visited two local clinics in the endemic area for CKDue on August 10, 2009 and 10 pedigrees of 10 of these cases with familial clustering of CKDue participated in this study. Urine samples, collected from affected patients (n = 106), unaffected relative controls (n = 81), and Japanese controls (n = 50), were analyzed for two tubular markers: α1-microglobulin and N-acetyl-β-d-glucosaminidase. Urine samples from patients with CKDue stages 1–4 (n = 101) and all the samples from unaffected relatives and Japanese controls were analyzed for urinary cadmium concentration.


Urinary excretion of α1-microglobulin was elevated even in the earliest stage of CKDue compared with its levels in unaffected relative controls. Urinary excretion of N-acetyl-β-d-glucosaminidase was elevated only in stage 5. In contrast, urinary cadmium excretion was similar in CKDue patients and in the unaffected relative controls, and levels in both these groups were significantly lower than the level in the Japanese controls. All levels were below the threshold level for renal toxicity, indicating the absence of any evidence of cadmium toxicity.


The present study indicates that renal tubular damage occurs in the very early stage of CKDue and demonstrates the existence of familial clustering, suggesting that CKDue is likely to be the outcome of exposure to an unknown nephrotoxin in susceptible subjects in the endemic region.


α1-Microglobulin N-acetyl-β-d-glucosaminidase Chronic kidney disease of uncertain etiology Urine Sri Lanka 

Supplementary material

12199_2011_224_MOESM1_ESM.pdf (77 kb)
Supplementary material 1 (PDF 77 kb)


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Copyright information

© The Japanese Society for Hygiene 2011

Authors and Affiliations

  • Shanika Nanayakkara
    • 1
  • S. T. M. L. D. Senevirathna
    • 1
  • Upul Karunaratne
    • 2
  • Rohana Chandrajith
    • 3
  • Kouji H. Harada
    • 1
  • Toshiaki Hitomi
    • 1
  • Takao Watanabe
    • 4
  • Tilak Abeysekera
    • 2
  • T. N. C. Aturaliya
    • 5
  • Akio Koizumi
    • 1
  1. 1.Department of Health and Environmental SciencesKyoto University Graduate School of MedicineKyotoJapan
  2. 2.Nephrology UnitGeneral Hospital (Teaching)KandySri Lanka
  3. 3.Department of Geology, Faculty of ScienceUniversity of PeradeniyaPeradeniyaSri Lanka
  4. 4.Tohoku Bunkyo CollegeYamagataJapan
  5. 5.Department of Pharmacology, Faculty of MedicineUniversity of PeradeniyaPeradeniyaSri Lanka

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