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
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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.
Keywordsα1-Microglobulin N-acetyl-β-d-glucosaminidase Chronic kidney disease of uncertain etiology Urine Sri Lanka
- 1.Statistical abstract. Department of Census and Statistics, Sri Lanka. 2009. http://www.statistics.gov.lk/abstract2009/Pages/index.htm.
- 2.Athuraliya TN, Abeysekera DT, Amerasinghe PH, Kumarasiri PV, Dissanayake. Prevalence of chronic kidney disease in two tertiary care hospitals: high proportion of cases with uncertain aetiology. Ceylon Med. 2009;54:23–5.Google Scholar
- 3.World Health Organization (WHO) country office Sri Lanka. News letters. http://www.whosrilanka.org/EN/Section1_76.htm. Accessed 20 Dec 2010.
- 4.Bandara JMRS, Senevirathna DMA, Dasanayake DMRSV, Herath V, Bandara JMRP, Abeysekara T, Rajapaksha KH. Chronic renal failure in cascade irrigation systems in Sri Lanka associated with elevated dietary cadmium levels, rice and fresh water fish (Thilapia). Environ Geochem Health. 2008;30:465–78.PubMedCrossRefGoogle Scholar
- 5.Bandara JM, Wijewardena HV, Liyanege J, Upul MA, Bandara. Chronic renal failure in Sri Lanka caused by elevated dietary cadmium: Trojan horse of the green revolution. Toxicol Lett. 2010;198:33–9.Google Scholar
- 8.Chandrajith R, Nanayakkara S, Itai K, Aturaliya TN, Dissanayake CB, Abeysekara T, Harada K, Watanabe T, Koizumi A. Chronic kidney disease of uncertain aetiology (CKDuee) in Sri Lanka: geographic distribution and environmental implications. Environ Geochem Health. 2011;33:267–78.PubMedCrossRefGoogle Scholar
- 11.National Kidney Foundation (NKF). KDOQI Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. http://www.kidney.org/professionals/KDOQI/guidelines_ckd/toc.htm. Accessed 20 Dec 2010.
- 14.Koizumi A Yoshinaga T, Harada K, Inoue K, Morikawa, Muroi J, Inoue S, Eslami B, Fujii S, Fujimine Y, Hachiya N, Koda S, Kusaka Y, Murata K, Nakatsuka H, Omae K, Saito N, Shimbo S, Takenaka K, Takeshita T, Todoriki H, Wada Y, Watanabe T, Ikeda M. Assessment of human exposure to polychlorinated and polybrominated diphenyl ethers in Japan using early 1980s and mid 1990s archive samples. Environ Res. 2005; 99:31–9.Google Scholar
- 17.Yamagami T, Suna T, Fukui Y, Ohashi F, Takada S, Sakurai H, Aoshima K, Ikeda M. Biological variations in cadmium, alpha 1-microglobulin, beta 2-microglobulin and N-acetyl-beta-d-glucosaminidase in adult women in a non-polluted area. Int Arch Occup Environ Health. 2008;81:263–71.PubMedCrossRefGoogle Scholar
- 18.Ikeda M, Ezaki T, Tsukahara T, Moriguchi J, Furuki K, Fukui Y, Ukai SH, Okamoto, Sakurai H. Critical evaluation of alpha1- and beta2-microglobulins in urine as markers of cadmium-induced tubular dysfunction. Biometals. 2004;17:539–41.Google Scholar
- 19.Kobayashi E, Suwazono Y, Uetani M, Inaba T, Oishi M, Kido T, Nishijo M, Nakagawa H, Nogawa K. Estimation of benchmark dose as the threshold levels of urinary cadmium, based on excretion of total protein, beta2-microglobulin, and N-acetyl-beta-d-glucosaminidase in cadmium nonpolluted regions in Japan. Environ Res. 2006;101:401–6.PubMedCrossRefGoogle Scholar
- 20.Uno T, Kobayashi E, Suwazono Y, Okubo Y, Miura K, Sakata K, Okayama A, Ueshima H, Nakagawa H, Nogawa K. Health effects of cadmium exposure in the general environment in Japan with special reference to the lower limit of the benchmark dose as the threshold level of urinary cadmium. Scand J Work Environ Health. 2005;31:307–15.PubMedCrossRefGoogle Scholar
- 22.Vincent C, Marceau M, Blangarin P, Bouic P, Madjar JJ, Revillard JP. Purification of alpha 1-microglobulin produced by human hepatoma cell lines. Biochemical characterization and comparison with alpha 1-microglobulin synthesized by human hepatocytes. Eur J Biochem. 1987;165:699–704.PubMedCrossRefGoogle Scholar