Transcriptomic suppression of immune and ECM stability in skeletal muscle of patients with chronic kidney disease
Luke A. Baker, Nicholas Eastley, Robert U. Ashford, Matthew Denniff, Matthew Graham-Brown, Emma L. Watson
Abstract
Chronic 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.
Introduction
Chronic kidney disease (CKD) is common, affecting around 14% of adults in England [1], for which there is no cure. A loss of muscle mass and strength (sarcopenia, which is now recognised as a disease in its own right [2]), is a frequent complication of CKD affecting around 28% of people with more advanced disease [3,4].
Materials and methods
CKD patients were recruited from nephrology outpatient clinicals at Leicester General Hospital, UK between December 2013 and January 2019, as part of the ExTra CKD trial (Ref/10/H0406/50).
Results
Of the planned matched pairs, one healthy control sample did not pass RNA quality control and a replacement was not available, resulting in 9 control and 10 CKD samples being included in the final analysis. Participant characteristics are shown in Table 1.
Discussion
This study reports a distinct transcriptomic profile of skeletal muscle in patients CKD, revealing significant downregulation of immune and extracellular matrix (ECM) pathways. Several innate immune transcripts with established roles in tissue surveillance and repair, including CD163, C1QC, MPEG1, and CXCL14, were markedly downregulated.
Acknowledgments
The views expressed are those of the author(s) and not necessarily those of the Kidney Care Appeal, the Stoneygate Trust, the NIHR or the Department of Health and Social Care. We thank Dr Douglas Gould and Dr Soteris Xenophontos for their help with the collection of the muscle biopsy samples.
Citation: Baker LA, Eastley N, Ashford RU, Denniff M, Graham-Brown M, Watson EL (2026) Transcriptomic suppression of immune and ECM stability in skeletal muscle of patients with chronic kidney disease. PLoS One 21(2): e0328947. https://doi.org/10.1371/journal.pone.0328947
Editor: Tomasz W. Kaminski, Versiti Blood Research Institute, UNITED STATES OF AMERICA
Received: July 9, 2025; Accepted: December 21, 2025; Published: February 24, 2026
Copyright: © 2026 Baker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files. The full RNA-seq data set together with the metadata is available at https://github.com/emmawatson0604/CKD-vs-Healthy-control-RNA-seq-data.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
