Pioneering research uses human muscle cells to better understand muscle loss in chronic kidney disease

01 November 2022

In a recent study published in the Journal of Cachexia, Sarcopenia and Muscle, our researchers from University of Leicester have, for the first time, developed a model using human muscle cells to identify factors that contribute to differences in muscle mass between patients with chronic kidney disease (CKD) and non-CKD patients.

CKD patients often experience skeletal muscle loss, leading to reductions in muscle mass, strength, and function. When there is muscle loss, weakness may be experienced and physical activity limited, leading to frailty. This not only impacts quality of life but also increases the risk of illness and death.

Protein and muscle loss

The processes that lead to muscle loss in CKD patients are not well understood. Studies in humans are complicated by external factors, such as diet and exercise, making it hard for scientists to pinpoint the causes of muscle loss.

Currently available research does, however, suggest that the process through which our cells make protein (protein synthesis), breakdown of proteins (protein degradation), and anabolic resistance (where muscle creation and maintenance are disrupted), play a big part in the build-up or loss of muscle mass.

The human muscle cell model

With our funding, Drs Luke Baker and Emma Watson and their team have developed a model using human muscle cells to gain a more accurate understanding of the causes of muscle loss in individuals living with CKD.

To do this, patients aged between 50 and 60 (the most common age of pre-dialysis CKD patients), were recruited. Half of the patients had CKD but were not undergoing dialysis, the other half did not have CKD. A pea-sized piece of muscle was taken from patient’s upper thigh, providing the muscle cells required for the experiments.

Using these human muscle cells, the team explored the effects of protein synthesis and breakdown on muscle loss in CKD patients. Importantly, they compared these samples to cells from non-CKD patients; the first time this has been done. Luke and Emma’s team also exposed cells to different doses of a hormone called insulin-like growth factor 1 (IGF-1), which stimulates protein synthesis and the growth of muscle, to see if there was a difference in response between CKD and non-CKD cells.

Dr Luke Baker

Promising results could help us to develop new treatment options

Results showed that cells from CKD patients had significantly higher levels of protein degradation, suggesting that the muscles of CKD patients experienced more breakdown than non-CKD patients. In addition, non-CKD patient cells exposed to IGF-1 showed an increase in protein synthesis, indicating muscle build up, but CKD patients showed very little response.

Through this innovative approach, the team have shown that CKD patients may lose muscle more quickly than non-CKD patients due to higher protein breakdown and are also not able to rebuild muscle mass in the same way as patients without a CKD diagnosis.

This new model, developed by the team at the University of Leicester with support from Kidney Research UK, offers an improved representation of the impact of CKD on human muscle, providing an important tool for further investigations into muscle loss. Excitingly, this model might also allow the testing of future treatments for muscle loss in CKD.

Luke said: “Our findings provide us with a vital tool enabling screening and development of future strategies to treat the muscular weakness and dysfunction commonly reported by people living with CKD. We are currently using these results to inform the development of future medications, to improve the quality of life of those who live with CKD and suffer from these debilitating symptoms”.

Dr Aisling McMahon, executive director of research and policy at Kidney Research UK said: “Maintaining good quality of life remains a key challenge for patients living with kidney disease, and understanding the biological mechanisms than can contribute to these problems is crucial. Luke and his team have taken an important step forward in pinpointing the causes of muscle loss and weakness that is so often reported by kidney patients, which will hopefully accelerate the assessment and development of new and effective solutions”.

Read the full paper to find out more.