title: Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study.
abstract: BACKGROUND
  In 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Significant 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).
  
  
  CONCLUSIONS
  A 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.
authors.affiliation: Cell Biology Group, National Institute of Fundamental Studies, Kandy, Sri Lanka.
authors.forename: Saravanabavan
authors.initials: S
authors.lastname: Sayanthooran
authors.affiliation: Cell Biology Group, National Institute of Fundamental Studies, Kandy, Sri Lanka. dmaganaarachchi@gmail.com.
authors.forename: Dhammika N
authors.initials: DN
authors.lastname: Magana-Arachchi
authors.affiliation: Renal Care & Research Centre, District Hospital, Girandurukotte, Sri Lanka.
authors.forename: Lishanthe
authors.initials: L
authors.lastname: Gunerathne
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka.
authors.forename: Tilak
authors.initials: T
authors.lastname: Abeysekera
mesh_terms: D015415:Biomarkers / Q000097:blood; D066246:ErbB Receptors / Q000097:blood*; D005240:Feasibility Studies; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000097:blood*; D005982:Glutathione Transferase / Q000097:blood*; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000097:blood*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015995:Prevalence; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013188:Sri Lanka / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D066246:ErbB Receptors; D005721:Glutamate-Cysteine Ligase; D005982:Glutathione Transferase; D000072596:Hepatitis A Virus Cellular Receptor 1; D018970:Insulin-Like Growth Factor Binding Protein 1; C491143:HAVCR1 protein, human; C032231:IGFBP1 protein, human; C512478:EGFR protein, human; C000609392:GCLC protein, human
keywords: Gene expression analysis; Kidney injury; Oxidative stress; RT-qPCR