What was the purpose of the study?

Many people with kidney disease suffer from multiple and diverse symptoms, which make normal daily activities more difficult. We were interested in understanding what specifically causes these problems to find ways that kidney patients can improve their health and well-being by making adjustments to their lifestyle.

This study investigated the role of various genes, cells, and factors in the blood, which may be involved in the complicated symptom burden and long-term health of kidney patients, and compared differences in these factors to healthy people of the same age, gender and ethnic background. Identification of these differences is an important step in designing new therapeutic interventions. This study particularly focussed on cardiovascular risk factors, muscle deterioration, and inflammation.

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

Participants were assessed at the start of the study, and five more times over a 36-month period. They had a blood sample and urine sample taken at each assessment, as well as human body measurements such as height, weight and fat mass. ). We also did some tests of physical function and fitness. Clinical records were accessed and assessed for up to five years after their last visit to gather data on the progression of the disease and outcomes.

Some of the genes, cells and factors in the blood that we are investigating in our studies are newly discovered and we do not know enough about them to fully understand our findings. We need to study them in more detail, and hope to find out:

• How the cells and factors change over time

• How the genes, cells and factors are related to one another

• How the genes, cells and factors are related to the long-term health of kidney patients

• How the genes, cells and factors differ between individual kidney patients (to help us tailor future treatments to the patients who will benefit the most)

• How the genes, cells and factors differ in kidney patients and healthy people

The longer-term aim is to identify and develop lifestyle interventions such as exercise to improve the health of people living with kidney disease.

Progress and main findings

37 people volunteered to participate in the study: 8 kidney transplant recipients, 14 people with early-stage chronic kidney disease (CKD) and 15 people who do not have kidney disease (controls). Lab analysis gave a wealth of information about differences in the blood cells and factors of people with kidney disease. The main findings were as follows:

• People with kidney disease have higher levels of inflammatory cytokines in their blood, which have been shown to be partially responsible for the muscle weakness noted in this population. Follow this link to the manuscript regarding these findings in more detail.

• People with kidney disease have higher levels of a compound called Chemerin in their blood and urine, which is related to high levels of inflammation and reduced muscle mass (manuscript currently in preparation).

• People with a kidney transplant can undertake high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) without negative effects on the immune cells in the blood. This was previously a concern to those who had received a kidney transplant and is the first research of its kind. Follow this link to the manuscript regarding these findings in more detail.

• Factors extracted from the blood of people with kidney disease can exert similar effects on muscle cells grown in the lab as we see in the living human being. This novel work will allow us to identify and target ways to prevent muscle loss and weakness in the future. Follow this link to the manuscript regarding these findings in more detail.

• We have identified a kidney disease-specific panel of blood proteins which may provide a quick and simple way to diagnose clinically significant loss of muscle mass or function. This work is being taken forward in our ongoing research studies.

Evidence

Details of the study can be viewed here.