ckdexplore

Muscle wasting is a common complication of chronic kidney disease (CKD) and is clinically important due to its association with morbidity and mortality.

Aside from a small amount of work performed using an animal model of CKD, there has been little research into the underlying causes of muscle loss in human CKD patients.

If we are better able to understand the mechanisms causing muscle wasting, we may be able to identify therapies to help patients gain muscle mass, or prevent further loss. An increased muscle mass is desirable in these patients, not only because muscle has strong positive metabolic and anti-inflammatory effects, but because it also increases quality of life and physical functioning, with the potential to reduce cardiovascular risk.

The Explore CKD study involves the collection of skeletal muscle biopsies from patients with CKD and matched healthy controls which will then be used to establish primary cultures through isolation of the progenitor cells. Using this model we can then determine how these cells respond to anabolic and catabolic agents, how they repair themselves following injury and the potential for exercise to be used as a therapy.

Understanding the mechanisms that initiate muscle wasting in this patient population will provide potential targets for a range of interventions including exercise recommendations through to small molecule inhibitor delivery.

 

Milestones

  • We have identified that when muscle cells collected from the patients are cultured outside of the uraemic environment they appear to retain their ability to respond to anabolic stimuli compared to healthy controls. However, once the cells are incubated together with patient serum impairments in signalling to protein synthesis occur. This suggests a molecule within uraemic serum may trigger protein wasting. These experiments are on-going.
  • We have identified 18 differentially expressed microRNA’s in skeletal muscle biopsies from CKD patients relative to aged and sexed matched healthy controls. MiRNAs are short non-coding RNA molecules that regulate gene and protein expression making them possible candidates for a role in muscle wasting in CKD. These miRNA’s are currently being validated in a larger number of individuals by PCR.
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