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      Chronic kidney disease of unknown aetiology in Sri Lanka: is cadmium a likely cause?

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          Abstract

          Background

          The rising prevalence of chronic kidney disease (CKD) and subsequent end stage renal failure necessitating renal replacement therapy has profound consequences for affected individuals and health care resources. This community based study was conducted to identify potential predictors of microalbuminuria in a randomly selected sample of adults from the North Central Province (NCP) of Sri Lanka, where the burden of CKD is pronounced and the underlying cause still unknown.

          Methods

          Exposures to possible risk factors were determined in randomly recruited subjects (425 females and 461 males) from selected areas of the NCP of Sri Lanka using an interviewer administered questionnaire. Sulphosalicylic acid and the Light Dependent Resister microalbumin gel filtration method was used for initial screening for microalbuminuria and reconfirmed by the Micral strip test.

          Results

          Microalbumnuria was detected in 6.1% of the females and 8.5% of the males. Smoking (p < 0.001), alcohol use (p = 0.003), hypertension (p < 0.001), diabetes (p < 0.001), urinary tract infection (UTI) (p = 0.034) and consumption of water from wells in the fields (p = 0.025) were associated with microalbuminuria. In the binary logistic regression analysis, hypertension, diabetes mellitus, UTI, drinking well water in the fields, smoking and pesticide spraying were found to be significant predictors of microalbuminuria.

          Conclusions

          Hypertension, diabetes mellitus, UTI, and smoking are known risk factors for microalbuminuria. The association between microalbuminuria and consumption of well water suggests an environmental aetiology to CKD in NCP. The causative agent is yet to be identified. Investigations for cadmium as a potential causative agent needs to be initiated.

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          Most cited references17

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          Microalbuminuria in the US population: third National Health and Nutrition Examination Survey.

          Microalbuminuria (MA) is associated with adverse health outcomes in diabetic and hypertensive adults. The prevalence and clinical significance of MA in nondiabetic populations is less clear. The purpose of this study was to generate national estimates of the prevalence of MA in the US population. Untimed urinary albumin concentrations (UACs) and creatinine concentrations were evaluated in a nationally representative sample of 22,244 participants aged 6 years and older. Persons with hematuria and menstruating or pregnant women were excluded from analysis. The percent prevalence of clinical proteinuria (UAC > or = 300 mg/L) was similar for males and females. However, the prevalence of MA (urinary albumin-creatinine ratio [ACR], 30 to 299 mg/g) was significantly lower in males (6.1%) compared with females (9.7%). MA prevalence was greater in children than young adults and increased continuously starting at 40 years of age. MA prevalence was greater in non-Hispanic blacks and Mexican Americans aged 40 to 79 years compared with similar-aged non-Hispanic whites. MA prevalence was 28.8% in persons with previously diagnosed diabetes, 16.0% in those with hypertension, and 5.1% in those without diabetes, hypertension, cardiovascular disease, or elevated serum creatinine levels. In adults aged 40+ years, after excluding persons with clinical proteinuria, albuminuria (defined as ACR > or = 30 mg/g) was independently associated with older age, non-Hispanic black and Mexican American ethnicity, diabetes, hypertension, and elevated serum creatinine concentration. MA is common, even among persons without diabetes or hypertension. Age, sex, race/ethnicity, and concomitant disease contribute to the variability of MA prevalence estimates. Copyright 2002 by the National Kidney Foundation, Inc.
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            Cadmium, diabetes and chronic kidney disease.

            Recent epidemiological studies suggest a positive association between exposure to the environmental pollutant cadmium (Cd) and the incidence and severity of diabetes. In this review, we examine the literature suggesting a relationship between Cd exposure, elevated blood glucose levels, and the development of diabetes. In addition we review human and animal studies indicating that Cd potentiates or exacerbates diabetic nephropathy. We also review the various possible cellular mechanisms by which Cd may alter blood glucose levels. In addition, we present some novel findings from our own laboratories showing that Cd elevates fasting blood glucose levels in an animal model of subchronic Cd exposure before overt signs of renal dysfunction are evident. These studies also show that Cd reduces insulin levels and has direct cytotoxic effects on the pancreas. Together, these findings indicate that Cd may be a factor in the development of some types of diabetes and they raise the possibility that Cd and diabetes-related hyperglycemia may act synergistically to damage the kidney.
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              Chronic renal failure among farm families in cascade irrigation systems in Sri Lanka associated with elevated dietary cadmium levels in rice and freshwater fish (Tilapia).

              Chronic renal failure (CRF), in the main agricultural region under reservoir based cascade irrigation in Sri Lanka has reached crisis proportion. Over 5,000 patients in the region are under treatment for CRF. The objective of this study is to establish the etiology of the CRF. Concentrations of nine heavy metals were determined in sediments, soils of reservoir peripheries, water and Nelumbo nucifera (lotus) grown in five major reservoirs that supply irrigation water. All five reservoirs carried higher levels of dissolved cadmium (Cd), iron (Fe) and lead (Pb). Dissolved Cd in reservoir water ranged from 0.03 to 0.06 mg/l. Sediment Cd concentration was 1.78-2.45 mg/kg. No arsenic (As) was detected. Cd content in lotus rhizomes was 253.82 mg/kg. The Provisional Tolerable Weekly Intake (PTWI) of Cd based on extreme exposure of rice is 8.702-15.927 microg/kg body weight (BW) for different age groups, 5-50 years. The PTWI of Cd due to extreme exposure of fish is 6.773-12.469 microg/kg BW. The PTWI on a rice staple with fish is 15.475-28.396 microg/kg BW. The mean urinary cadmium (UCd) concentration in CRF patients of age group 40-60 years was 7.58 microg Cd/g creatinine and in asymptomatic persons UCd was 11.62 microg Cd/g creatinine, indicating a chronic exposure to Cd. The possible source of Cd in reservoir sediments and water is Cd-contaminated agrochemicals. The CRF prevalent in north central Sri Lanka is a result of chronic dietary intake of Cd, supported by high natural levels of fluoride in drinking water, coupled with neglecting of routine de-silting of reservoirs for the past 20 years.
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                Author and article information

                Journal
                BMC Nephrol
                BMC Nephrology
                BioMed Central
                1471-2369
                2011
                5 July 2011
                : 12
                : 32
                Affiliations
                [1 ]Department of Medicine, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
                [2 ]Department of Physiology, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
                [3 ]Section of Epidemiology and Biostatistics, University of Auckland, Auckland, New Zealand
                [4 ]Department of Public health, University of Kelaniya, Ragama, Sri Lanka
                Article
                1471-2369-12-32
                10.1186/1471-2369-12-32
                3143923
                21726464
                b44fd4c9-a51a-484a-aae8-f0a8db26e115
                Copyright ©2011 Wanigasuriya et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 December 2010
                : 5 July 2011
                Categories
                Research Article

                Nephrology
                cadmium,aetiology,chronic kidney disease
                Nephrology
                cadmium, aetiology, chronic kidney disease

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