Uncovering potential biomarkers for chronic kidney disease of unknown etiology through a network-based bioinformatic...

Area of Science:

• Nephrology
• Bioinformatics
• Molecular Biology

Background:

• Chronic kidney disease of unknown cause (CKDu) is defined by a sustained decline in estimated glomerular filtration rate (eGFR) without identifiable risk factors.
• Biopsy studies indicate that renal tubular injury plays a significant role in the pathogenesis of CKDu.

Purpose of the Study:

• To employ a network-based bioinformatics approach to identify potential biomarkers and elucidate their roles in CKDu.
• To pinpoint key genes and pathways implicated in the initiation and progression of renal tubular injury in CKDu.

Main Methods:

• Conducted a comprehensive literature survey across PubMed, Scopus, and Science Direct, focusing on renal tubular injury markers.
• Utilized network analysis with Cytoscape and enrichment analysis with Cluego on 43 identified genes associated with CKDu.
• Analyzed topological properties and functional enrichment of selected genes to identify hub genes and biological pathways.

Main Results:

• Identified 37 biomarkers and 43 corresponding genes from 40 research articles related to CKDu.
• SPP1 emerged as the hub gene, with SPP1, TNF, CLU, CST3, CRP, TGFB1, and IL-6 ranking highest in network centrality.
• Functional analysis indicated localization to collagen type IV trimers in renal tubules and monooxygenase activity for detoxification, with TLR signaling implicated in inflammation.

Conclusions:

• The identified genes (SPP1, TNF, CLU, CST3, CRP, TGFB1, IL-6) are critically involved in the initiation and progression of CKDu.
• These genes and associated pathways represent promising candidates for further investigation as diagnostic and prognostic biomarkers for CKDu.
• Biological validation studies are necessary to confirm the biomarker potential of these identified genes in CKDu.