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bioRxiv · 10.1101/2025.07.11.664285

Transcriptomic Suppression of Immune and Regenerative Signalling in Skeletal Muscle of Patients with Chronic Kidney Disease

Baker, L.·Eastley, N.·Ashford, R.·Denniff, M.·Graham-Brown, M.·Watson, E.
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Abstract

BackgroundChronic kidney disease (CKD) is a growing public health emergency with a global prevalence of approximately 14%. Sarcopenia is a common complication of CKD contributing to functional decline and poor outcomes. However, the molecular mechanisms driving muscle wasting in CKD remain incompletely understood. This study aimed to characterise the transcriptomic profile in individuals with CKD compared to healthy control counterparts, to identify key pathways implicated in muscle dysfunction. MethodsVastus lateralis muscle biopsy samples were obtained from n=10 people with CKD and n=9 healthy controls matched for age, sex, ethnicity and physical activity. Bulk RNA sequencing was performed on all samples. Differential gene expression was assessed using DESeq2 and pathway enrichments analyses were conducted using Gene Ontology (GO) and KEGG databases. ResultsA total of 76 genes were differentially expressed in CKD muscle (FDR < 0.05, |log2FC| [&ge;] 1), with 62 downregulated and 14 upregulated. Transcriptomic analysis revealed suppression of immune-related pathways, including leukocyte chemotaxis and macrophage-associated signalling (e.g., CD163, CXCL14, MPEG1). GO and KEGG analyses further supported downregulation of immune surveillance and inflammatory pathways. Several genes implicated in muscle regeneration (e.g., MEGF10, PODN, SOX4) were also differentially expressed, suggesting impaired regenerative signalling. Classical markers of myogenesis and protein degradation were unchanged, indicating a blunted rather than overtly inflammatory or catabolic muscle environment. ConclusionsSkeletal muscle in CKD exhibits a distinct transcriptional profile marked by suppression of immune and regenerative processes. These findings refine our understanding of CKD-associated sarcopenia and may inform the development of targeted therapeutic strategies beyond conventional exercise-based interventions.

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Baker, L., Eastley, N., Ashford, R., Denniff, M., Graham-Brown, M., Watson, E.. 2025-07-14. Transcriptomic Suppression of Immune and Regenerative Signalling in Skeletal Muscle of Patients with Chronic Kidney Disease. https://doi.org/10.1101/2025.07.11.664285

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