Sarcopenia in Haemodialysis: Molecular Mechanisms and the Effects of Neuromuscular Electrical Stimulation

Supervisors:

• Dr Emma Watson Emma.watson@leicester.ac.uk
• Professor James Burton Jb343@leicester.ac.uk

Project description:

Sarcopenia, characterised by a loss of skeletal muscle strength and mass, is increasingly recognised as a major complication of chronic kidney disease (CKD)[1]. Individuals receiving haemodialysis (HD) experience particularly high rates of muscle wasting and functional decline, contributing to reduced quality of life, increased hospitalisation and premature mortality[2]. Estimates suggest that sarcopenia affects approximately 28–40% of patients with advanced CKD, highlighting the scale of this clinical problem[3-5].

Despite its clinical importance, we know little about the underling causes of sarcopenia in the HD population, or have any validated treatment options. The NIHR-funded STIM-HD study (a multi-centre RCT) is investigating the efficacy of neuromuscular electrical stimulation (NMES) as a treatment for sarcopenia in HD patients. This PhD project will utilise skeletal muscle biopsies collected as part of this trial to investigate potential mechanisms of muscle wasting in this population, and the effect of the intervention upon muscle phenotype.

The first component of the PhD will focus on characterising the prevalence and clinical manifestations of sarcopenia in haemodialysis patients within the STIM-HD cohort. Using clinical data collected from this study which includes muscle strength, muscle mass, physical function, body composition and patient-reported outcomes, this work will provide a detailed description of muscle impairment in this population and explore relationships between sarcopenia and symptoms such as fatigue, reduced physical performance and quality of life.

The second component of the PhD will compare the molecular phenotype of skeletal muscle of patients receiving HD to a healthy control population. This will involve measures of fibre size, fibre type, mitochondrial function and changes to the muscle transcriptome and proteome. This will allow for the identification of dysregulated molecular pathways involved in muscle atrophy, regeneration, inflammation and metabolic regulation. 

The third component of the PhD will investigate the effect of the NMES intervention within muscle biopsy samples collected from the STIM-HD study. It will examine changes to muscle fibre size, fibre type, mitochondrial number and structure and to the transcriptome and proteome. 

Together, these complementary approaches will provide one of the most comprehensive molecular characterisations of skeletal muscle in haemodialysis patients to date. The findings will generate new insights into the biological mechanisms underlying sarcopenia in CKD and may identify novel therapeutic targets to improve muscle health and physical function in this vulnerable population.

The project will provide the successful student with multidisciplinary training in clinical research, skeletal muscle biology, multi-omics data analysis and advanced imaging techniques, while contributing to a major NIHR-funded clinical trial.

References:

1. Moorthi, R.N. and K.G. Avin, Clinical relevance of sarcopenia in chronic kidney disease. Curr Opin Nephrol Hypertens, 2017. 26(3): p. 219-228.
2. Zicarelli, M., et al., Comprehensive Insights into Sarcopenia in Dialysis Patients: Mechanisms, Assessment, and Therapeutic Approaches. Medicina (Kaunas), 2025. 61(3).
3. John, S.G., et al., Natural history of skeletal muscle mass changes in chronic kidney disease stage 4 and 5 patients: an observational study. PLoS One, 2013. 8(5): p. e65372.
4. Shu, X., et al., Diagnosis, prevalence, and mortality of sarcopenia in dialysis patients: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle, 2022. 13(1): p. 145-158.
5. Wathanavasin, W., et al., Prevalence of Sarcopenia and Its Impact on Cardiovascular Events and Mortality among Dialysis Patients: A Systematic Review and Meta-Analysis. Nutrients, 2022. 14(19).