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Evaluation of biochemical profile of Chronic Kidney Disease of uncertain etiology in Sri Lanka.

ABSTRACT: Chronic Kidney Disease of uncertain etiology (CKDu) is an endemic, disease that mostly affects young agricultural workers in the rural dry zone of Sri Lanka. This study was designed to identify specific biochemical manifestations of CKDu cases. All (119) non-dialysis definite CKDu patients in Girandurukotte and Wilgamuwa were selected. Blood and urine samples were collected and measured biochemical parameters. All analyses were performed in IBM SPSS statistics version 23 (IBM Corp, USA). The median blood pressure was normal though nearly half of the patients (45.4%) who were in the advanced stages (Stage 3b, 4 and 5) of CKDu. Patients without a history of hypertension before the diagnosis of CKDu (100%) and minimal proteinuria (26%) are similar to the previous findings. Patients without a history of diabetes before the CKDu diagnosis had high percentages of diabetes (15.7%) and pre-diabetes (59.8%) and hence indicated the possibility of uremia induced impaired glucose intolerance in the rural areas of the country. There were 62.2% patients who had low vitamin D and only a minority had evidence of bone mineral diseases. Out of liver disease markers serum glutamic pyruvic transaminases (SGPT), serum glutamic oxaloacetic transaminases (SGOT), gamma-glutamyl transferase (GGT), and Lactic acid degydrogenase (LDH) had an inverse correlation with the advancement of the disease indicating subclinical liver disease. Osmolality in serum and urine showed a discrepancy despite > 50% of CKDu patients had increased their serum osmolality. The current study supports most of the previously described manifestations of CKDu. Moreover, some specific patterns have been identified which need to be validated in a larger group.

SUBMITTER: Fernando BNTW

PROVIDER: S-EPMC7197770 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Evaluation of biochemical profile of Chronic Kidney Disease of uncertain etiology in Sri Lanka.

Fernando Buddhi N T W BNTW Sudeshika Thilini S H TSH Hettiarachchi Thilini W TW Badurdeen Zeid Z Abeysekara Thilak D J TDJ Abeysundara Hemalika T K HTK Jayasinghe Sakunthala S Ranasighe Shirani S Nanayakkara Nishantha N

PloS one 20200504 5

Chronic Kidney Disease of uncertain etiology (CKDu) is an endemic, disease that mostly affects young agricultural workers in the rural dry zone of Sri Lanka. This study was designed to identify specific biochemical manifestations of CKDu cases. All (119) non-dialysis definite CKDu patients in Girandurukotte and Wilgamuwa were selected. Blood and urine samples were collected and measured biochemical parameters. All analyses were performed in IBM SPSS statistics version 23 (IBM Corp, USA). The med ...[more]

PMID: 32365131

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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.

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Evaluation of biochemical profile of Chronic Kidney Disease of uncertain etiology in Sri Lanka.

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Evaluation of biochemical profile of Chronic Kidney Disease of uncertain etiology in Sri Lanka.

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