Epigenetic Regulation of Muscle Wasting in End-Stage Renal Failure
Research type
Research Study
Full title
The role of microRNAs, residual renal function and inflammation in muscle wasting in end-stage kidney disease
IRAS ID
212413
Contact name
Edwina Brown
Contact email
Sponsor organisation
Joint Research Compliance Office
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Premature muscle tiring (fatigue) is an important complication of advanced kidney disease, and results in reduced ability to walk and exercise. As patients move from pre-dialysis care to dialysis, they begin to lose their residual kidney function, and experience muscle wasting. The effect of dialysis mode (peritoneal dialysis, PD, and haemodialysis, HD) on muscle wasting is not known.
Muscle wasting also occurs in other chronic diseases like chronic obstructive pulmonary disease (COPD). In COPD, we have identified a role for microRNAs (small RNAs that inhibit the translation or promote degradation of specific mRNAs) in the development of muscle weakness. Muscle-enriched microRNAs can be measured in plasma as markers of ongoing wasting.
We shall recruit patients from Imperial NHS Healthcare Trust who are starting / due to start dialysis soon. With ultrasound and bio-impedance, we will see how muscle bulk and strength changes with regular dialysis. We will determine physical activity changes before and whilst on dialysis. Using blood and optional muscle biopsy samples, we shall investigate molecular mechanisms involved in muscle fatigue in end-stage kidney disease, focusing on microRNAs. In muscle we will quantify the expression of microRNAs shown to promote atrophy and in plasma we will quantify inflammatory markers, muscle-enriched microRNAs and other microRNAs that associate with muscle mass as markers of ongoing wasting or the susceptibility to wasting. Patient follow-up will be for one year, with study duration including recruitment expected to be three years.
This prospective observational trial will determine the effect of PD and HD on residual renal function, inflammation and muscle wasting. It will also determine whether wasting in ESKD has the same microRNA profile as in COPD and whether wasting can be detected early by measuring circulating microRNAs. The contribution of muscle wasting to progressive frailty, hospitalization episodes and mortality will be evaluated.
REC name
London - Camberwell St Giles Research Ethics Committee
REC reference
17/LO/0426
Date of REC Opinion
19 Apr 2017
REC opinion
Further Information Favourable Opinion