What was the purpose of the study?

Kidney disease can cause muscle wasting (when the muscles waste away), which leads to weakness, fatigue, and reduced physical functioning. This can start early on in the disease, and is thought to play an important role in the way the disease progresses, and even the patients’ ultimate chance of survival. Currently, the exact cause of muscle wasting in CKD is not known, and so further research is needed to better understand and treat this complication. Explore CKD aimed to better understand the mechanisms of muscle wasting in the CKD population by analysing skeletal muscle in the laboratory from patients and comparing it to healthy adults to find out what is different in the muscle of CKD patients and what the cause of their muscle loss may be.

What did it involve and what did we hope to find out?

If a participant decided to take part in this study we arranged for them to visit us in the hospital on one occasion. This involved having a muscle biopsy from a muscle in their thigh, as well as a blood test, and an ultrasound of their leg. We also asked the participant to complete a questionnaire on their physical activity levels. The muscle and blood samples were analysed at the University of Leicester for molecules important to muscle loss, growth, and repair, and compared to the same measures in a matched healthy control. We hoped to discover and understand what mechanisms cause patients with CKD to lose muscle mass and function. We hope that this study will help us to design improved treatments and interventions for kidney patients in the future.

Progress and main findings

The study ran between September 2017 and February 2019. We collected blood samples and skeletal muscle biopsies from 25 people with CKD and 46 people without CKD.

The main findings were as follows :

  • People with CKD have higher levels of inflammation in the muscle tissue itself. Higher levels of inflammation have been shown to be one of the reasons for poor muscle mass and function in those with CKD. We were also able to show that exercise doesn't exert the same anti-inflammatory effect in those with CKD as it does in those without CKD. Future work will investigate why this in the case and what we can do to alter this response so that those with CKD can get the same biological benefits of exercise as those without CKD. Follow this link to the manuscript regarding these findings in more detail.

  • People with CKD have a reduced amount of mitochondria in their muscle tissue. Mitochondria are often called 'the powerhouse of the cell' and play a vital role in cellular energy production. The fact that those with CKD have a reduced number in their muscle tissue may contribute to the muscle fatigue and weakness noted in these people. This was also not altered with exercise and future work will seek to work out why this is and what we can do to improve mitochondrial number and function in CKD. Follow this link to the manuscript regarding these findings in more detail.

  • The muscle cells of people with CKD are more sensitive to a factor called chemerin than the muscle cells of those without CKD, which contributes to the high level of muscle tissue inflammation noted above. We have also shown how chemerin affects muscle in CKD and future work will look to understand how we can intervene in this process to improve muscle mass and function in CKD (manuscript currently in preparation).

  • When grown in the lab, muscle cells from people with CKD retain many of the characteristics that they show in the living muscle. This is an important and exciting discovery as it means we can use lab-grown cells to model the intricacies of CKD muscle wasting, dysfunction and fatigue, and test potential therapeutic agents in the lab before giving them to patients. Follow this link to the manuscript regarding these findings in more detail.

Evidence

Details of the trial can be found here. Publications including the data from EXPLORE-CKD can be viewed here.