Dataset Information

Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: a cohort study in Medawachchiya, Sri Lanka.

ABSTRACT:

Background

The alarming rise in the prevalence of chronic kidney disease of uncertain etiology (CKDu) among the low socioeconomic farming community in the North Central Province of Sri Lanka has been recognized as an emerging public health issue in the country.

Methods

This study sought to determine the possible factors associated with the progression and mortality of CKDu. The study utilized a single-center cohort registered in 2003 and followed up until 2009 in a regional clinic in the endemic region, and used a Cox proportional hazards model.

Results

We repeatedly found an association between disease progression and hypertension. Men were at higher risk of CKDu than women. A significant proportion of the patients in this cohort were underweight, which emphasized the need for future studies on the nutritional status of these patients.

Conclusions

Compared with findings in western countries and other regions of Asia, we identified hypertension as a major risk factor for progression of CKDu in this cohort.

SUBMITTER: Senevirathna L

PROVIDER: S-EPMC3348239 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Publications

Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: a cohort study in Medawachchiya, Sri Lanka.

Senevirathna Lalantha L Abeysekera Tilak T Nanayakkara Shanika S Chandrajith Rohana R Ratnatunga Neelakanthi N Harada Kouji H KH Hitomi Toshiaki T Komiya Toshiyuki T Muso Eri E Koizumi Akio A

Environmental health and preventive medicine 20110901 3

<h4>Background</h4>The alarming rise in the prevalence of chronic kidney disease of uncertain etiology (CKDu) among the low socioeconomic farming community in the North Central Province of Sri Lanka has been recognized as an emerging public health issue in the country.<h4>Methods</h4>This study sought to determine the possible factors associated with the progression and mortality of CKDu. The study utilized a single-center cohort registered in 2003 and followed up until 2009 in a regional clinic ...[more]

PMID: 21881957

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Project description: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.

Project description:BackgroundIn Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). Identification of novel biomarkers that are customized to the specific causative factors would lead to early diagnosis and clearer prognosis of the diseases. This study aimed to find genetic biomarkers in blood to distinguish and identify CKDu from CKD as well as healthy populations from CKDu endemic and non-endemic areas of Sri Lanka.MethodsThe expression patterns of a selected panel of 12 potential genetic biomarkers were analyzed in blood using RT-qPCR. Fold changes of gene expressions in early and late stages of CKD and CKDu patients, and an apparently healthy population of a CKDu endemic area, Girandurukotte (GH) were calculated relative to apparently healthy volunteers from a CKDu non-endemic area, Kandy (KH) of Sri Lanka, using the comparative CT method.ResultsSignificant differences were observed between KH and early stage CKDu for both the insulin-like growth factor binding protein 1 (IGFBP1; p?=?0.012) and kidney injury molecule-1 (KIM1; p?=?0.003) genes, and KH and late stage CKD and CKDu for the glutathione-S-transferase mu 1 (GSTM1; p?<?0.05) gene. IGFBP1 and KIM1 genes showed significant difference between the early and late stage CKDu (p?<?0.01). The glutamate cysteine ligase catalytic subunit (GCLC) gene had significantly different expression between KH and all the other study groups (p?<?0.01). The GH group was significantly different from the KH group for the oxidative stress related genes, G6PD, GCLC and GSTM1 (p?<?0.01), and also the KIM1 gene (p?=?0.003). IGFBP1, insulin-like growth factor binding protein 3 (IGFBP3), fibronectin 1 (FN1) and KIM1 showed significant correlations with serum creatinine, and IGFBP1, KIM1 and kallikrein 1 (KLK1) with eGFR (p?<?0.05).ConclusionA panel consisting of IGFBP1, KIM1, GCLC and GSTM1 genes could be used in combination for early screening of CKDu, whereas these genes in addition with FN1, IGFBP3 and KLK1 could be used to monitor progression of CKDu. The regulation of these genes has to be studied on larger populations to validate their efficiency for further clinical use.

Project description:BackgroundIncrease in the number of cases in Chronic Kidney Disease of Unknown etiology (CKDu) in Sri Lanka has become a health issue of national concern. Even though, Northern Province is not identified as a high-risk province, there is an increasing trend of CKDu after the end of civil war in the Northern Province.MethodsThe present study was conducted in Thunukkai Division in Mullaitivu District to investigate the socio demographic and clinical pattern of CKDu patients and to evaluate the quality of their water sources. The samples were selected by using stratified purposive random sampling method which represented 29% of total CKDu patients in Thunukkai Division. Pretested structured questionnaire was administered to collect the data from the CKDu patients. The association between serum creatinine excreted by CKDu patients and the water quality parameters were determined by using linear regression model.ResultsAmong the patients, 80% were male with over 68% falling in the age range of 50-70. Majority (90%) were involved in agriculture related occupation. Smoking and alcohol consumption were detected as common habits among 40% of the patients. Secondarily developed, hypertension (60%) and diabetes (34%) were reported as common diseases in the area. Dug wells served as the commonest source of drinking water in the area (90% households) together with few tube wells. Physicochemistry of more than 50% of the water samples revealed higher electric conductivity, salinity, total dissolved solids, total hardness and Na levels compared to drinking water standards in Sri Lanka.ConclusionsSerum creatinine levels of the CKDu patients were significantly and negatively correlated with phosphate while positively correlated with total dissolved solids (TDS) and arsenic content of the drinking water. Geospatial mapping of TDS and arsenic in drinking water with the occurrence of higher serum creatinine levels confirmed the same trend. Thus, the total dissolved solids and arsenic in drinking water may have positive correlation with the occurrence of CKDu in Thunukkai region in the Mullaitivu District of Sri Lanka.

Dataset Information

Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: a cohort study in Medawachchiya, Sri Lanka.

Background

Methods

Results

Conclusions

Publications

Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: a cohort study in Medawachchiya, Sri Lanka.

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