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

Saravanabavan Sayanthooran,Lishanthe Gunerathne,Dhammika N Magana-Arachchi,Tilak Abeysekera

doi:10.1186/s12882-017-0440-x

Abstract

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.

Highlights

In Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu)
The most sensitive marker of CKD progression in clinical practice is proteinuria, especially when combined with the estimated glomerular filtration rate [2]; the process of kidney injury starts with the induction of molecular level changes, which gives promise for identification of molecular markers for early diagnosis of disease process
The etiologies for CKD differ and comorbidities exist in most CKD patients, a single biomarker would be incapable of satisfying all these needs [1, 2]

Summary

Introduction

In Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). The concept of biomarker discovery in medicine is becoming increasingly important due to its potential for early screening, more effective treatment and a more personalized approach to medical care [2].“A biological marker (biomarker) is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”[3] The biomarkers could be identified at any level along the Sayanthooran et al BMC Nephrology (2017) 18:31 genome – phenome continuum, and could be genomic biomarkers (DNA or RNA), proteomic biomarkers (proteins) or metabolic biomarker (metabolites) [3] Biomarkers in both acute kidney injury (AKI) and CKD look for similar effects of the diseases; decrease in nephron number, vascular insufficiency, and cell cycle disruption [1]. The etiologies for CKD differ and comorbidities exist in most CKD patients, a single biomarker would be incapable of satisfying all these needs [1, 2]

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