Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka

Saravanabavan, Sayanthooran; Magana-Arachchi, Dhammika; Gunerathne, Lishanthe; Abeysekera, Tilak; Ranaweera, L. T.

doi:10.1155/2016/7546265

Cited by 18 publications

(9 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up regulation of the GCLC and GSTM1 genes in the Girandurukotte healthy population compared to Kandy healthy population has been documented in a separate cohort [51] and has been hypothesized to be due to the environmental oxidative stressors that the population may be exposed to. These genes therefore hold potential as early screening markers, but needs further follow-up and testing.…”

Section: Discussionmentioning

confidence: 99%

Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study

Saravanabavan

Magana-Arachchi

Gunerathne³

et al. 2017

BMC Nephrol

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study

Saravanabavan

Magana-Arachchi

Gunerathne³

et al. 2017

BMC Nephrol

Self Cite

View full text Add to dashboard Cite

show abstract

“…A similar study was conducted to assess gene expression changes associated with oxidative stress in CKD and CKDu patients in comparison to healthy controls from CKDu endemic and non-endemic areas. Compared to the controls from non-endemic areas, genes coding for glutamate-cysteine ligase catalytic subunit (GCLC), glutathioneS-transferasemu1 (GSTM1), fibroblast growth factor-23 (FGF23), and NLR family pyrin domain containing 3 (NLRP3) were upregulated in CKD and CKDu patients in varying degrees [ 83 ]. These studies indicate that redox imbalance may play a mechanistic role in initiation or progression of this disease, and oxidative stress markers may serve as early biomarkers of renal cellular dysfunction.…”

Section: Current Use Of Novel Biomarkers In Ckdu Hotspots and Theimentioning

confidence: 99%

The Utility of Novel Renal Biomarkers in Assessment of Chronic Kidney Disease of Unknown Etiology (CKDu): A Review

Gunasekara

Silva

Herath

et al. 2020

IJERPH

View full text Add to dashboard Cite

Chronic Kidney Disease (CKD) is a globally prevalent non-communicable disease with significant mortality and morbidity. It is typically associated with diabetes and hypertension; however, over the last two decades, an emergence of CKD of unknown etiology (CKDu) has claimed thousands of lives in several tropical agricultural communities. CKDu is associated with gradual loss of renal function without initial symptoms until reaching complete kidney failure and eventually death. The most impacted are young adult males of lower socio-economic strata. Since the disease progression can be successfully attenuated through early detection, the development of superior screening and management measures is of utmost importance. In contrast to the conventional biomarkers, novel biomarkers with improved sensitivity and specificity are being discussed as promising tools for early diagnosis of the disease. This review summarizes emerging novel biomarkers used in assessing CKD and discusses the current utility and diagnostic potential of such biomarkers for CKDu screening in clinical settings of different communities impacted by CKDu. Our goal is to provide a framework for practitioners in CKDu impacted regions to consider the use of these novel biomarkers through this synthesis. The increased use of these biomarkers will not only help to validate their diagnostic power further and establish potential prognostic value but may also provide critical insights into sites and mechanisms of renal damage.

show abstract

“…Notably, while KIM-1 and NGAL remain more widely used in higher income countries, clinical use of these markers remain novel in the clinical settings of low-middle income countries. Recently, a few comparative studies in Sri Lanka have demonstrated the applicability of several novel biomarkers along with conventional markers in CKDu screening [11,12,17]. To date a comprehensive assessment of novel biomarkers in communities with diverse occupational and socioeconomic strata in different climatic zones has not been performed in Sri Lanka.…”

Section: Introductionmentioning

confidence: 99%

Applicability of Novel Urinary Biomarkers for the Assessment of Renal Injury in Selected Occupational Groups in Sri Lanka: A Comparative Study with Conventional Markers

Ekanayake

Gunasekara

Silva

et al. 2022

IJERPH

View full text Add to dashboard Cite

Screening approaches with more robust biomarkers, are of the utmost importance in the characterization of renal injuries, particularly among communities with high burdens of chronic kidney disease of uncertain etiology (CKDu). The present study aimed to assess the utility of two emerging biomarkers: kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in predicting renal injury in different occupational groups in Sri Lanka. A cross-sectional study was conducted with six occupational groups (n = 188): fisherfolk (FF), paddy farmers (PF), sugarcane farmers (SF), factory workers (FW) and plantation workers (PW) to assess the predictive performance of KIM-1 and NGAL against a CKDu patient (PT) group (n = 40). The median KIM-1 levels of the study groups; FF, PF, SF, FW, PW and PT were 0.67, 0.59, 0.49, 1.62, 0.67 and 5.24 ng/mgCr, respectively, while the median NGAL levels were 1.16, 2.52, 1.42, 1.71, 1.06 and 22.41 ng/mgCr respectively. In ROC analysis to predict CKDu susceptibility, the area under the curve for KIM-1 ranged from 0.88 to 0.99 for the study groups, and in overall analysis, the sensitivity and specificity were 100% and 96%, respectively, for a cutoff value of 2.76 ng/mgCr. Similarly, for NGAL the range of AUC was 0.78–0.94, and a cutoff value of 3.12 ng/mgCr produced 88% sensitivity and 82% specificity. Compared with conventional markers, KIM-1 was the best biomarker for the characterization of renal injury in the participants of the occupational groups. With further validations, KIM-1 may be adopted as a prognostic marker to identify early renal injury and CKDu susceptibilities in community screening.

show abstract

Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka

Cited by 18 publications

References 45 publications

Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study

Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study

The Utility of Novel Renal Biomarkers in Assessment of Chronic Kidney Disease of Unknown Etiology (CKDu): A Review

Applicability of Novel Urinary Biomarkers for the Assessment of Renal Injury in Selected Occupational Groups in Sri Lanka: A Comparative Study with Conventional Markers

Contact Info

Product

Resources

About