Non-dialyzable uremic toxins and renal tubular cell damage in CKD patients: a systems biology approach

Abstract

Abstract Background Chronic kidney disease presents global health challenges, with hemodialysis as a common treatment. However, non-dialyzable uremic toxins demand further investigation for new therapeutic approaches. Renal tubular cells require scrutiny due to their vulnerability to uremic toxins. Methods In this study, a systems biology approach utilized transcriptomics data from healthy renal tubular cells exposed to healthy and post-dialysis uremic plasma. Results Differential gene expression analysis identified 983 up-regulated genes, including 70 essential proteins in the protein–protein interaction network. Modularity-based clustering revealed six clusters of essential proteins associated with 11 pathological pathways activated in response to non-dialyzable uremic toxins. Conclusions Notably, WNT1/11, AGT, FGF4/17/22, LMX1B, GATA4, and CXCL12 emerged as promising targets for further exploration in renal tubular pathology related to non-dialyzable uremic toxins. Understanding the molecular players and pathways linked to renal tubular dysfunction opens avenues for novel therapeutic interventions and improved clinical management of chronic kidney disease and its complications.

Keywords

• Non-dialyzable uremic toxins
• Renal tubular cells
• Systems biology
• Pathological pathways
• Therapeutic targets