Abstract: TH-PO830
Effect of IV-Iron on Markers of Skeletal Muscle Health in Iron Deficient CKD Patients: Initial Findings From the Iron and Muscle Study
Session Information
- Health Maintenance, Nutrition, Metabolism
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance‚ Nutrition‚ and Metabolism
- 1400 Health Maintenance‚ Nutrition‚ and Metabolism
Authors
- Baker, Luke A., University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
- Oliveira, Benjamin A., King's College London, London, London, United Kingdom
- Parker, Nicola, University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
- Bramham, Kate, King's College Hospital NHS Foundation Trust, London, London, United Kingdom
- Greenwood, Sharlene A., King's College Hospital NHS Foundation Trust, London, London, United Kingdom
- Macdougall, Iain C., King's College Hospital NHS Foundation Trust, London, London, United Kingdom
- Okonko, Darlington, King's College London, London, London, United Kingdom
- Smith, Alice C., University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
- Watson, Emma L., University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
Background
Many people with chronic kidney disease (CKD) present with non-anaemic iron deficiency but are not routinely offered intravenous iron (IV) supplementation. With this population known to present with impaired muscle health, and previous studies showing a cardiovascular benefit of IV-iron usage, the Iron & Muscle study investigated the effect of 4-weeks IV iron on skeletal muscle function and health; we now report initial results from a mechanistic muscle biopsy sub-study.
Methods
This was a prospective, double-blind multicentre randomised controlled trial in 75 non-dialysis CKD patients with non-anaemic iron deficiency, of which 29 provided samples for the sub-study, Patients were randomly assigned to either; IV-Iron or placebo. and muscle biopsy samples were taken pre and 4 weeks post-intervention. This initial analysis involved mRNA expression analysis of indicators of mitochondrial biogenesis, protein turnover and inflammation. Baseline samples were also collected from healthy volunteers (HV, n=6) and non-iron deficient CKD controls (CKD, n=8) to allow for cohort comparisons.
Results
At baseline, significantly higher mRNA expression of several markers was seen in ID-CKD compared to CKD and HV cohorts: SOD2 (vs. HV p=0.021; vs. CKD p=0.016); Parkin (vs. HV p<0.001; vs. CKD p<0.001); TNFa(vs. HV p=0.032; vs. CKD p=0.012). A significant reduction in Murf-1 was noted in the CKD cohort in relation to both the ID-CKD cohort (p=0.001) as well as the HV cohort (p=0.011). No further differences were noted in relation to other markers of mitochondrial biogenesis, oxidative stress, or inflammation. Initial analysis of the effect of 4-weeks of IV-Iron in our ID-CKD cohort showed no significant change in any of our panel of markers related to mitochondrial biogenesis, inflammation, or oxidative stress.
Conclusion
This preliminary analysis suggests that skeletal muscle in those with ID-CKD have elevated levels of oxidative stress, mitophagy and inflammation in comparison to those without ID and HV. The use of 4-week IV-Iron does not influence any of these markers at the transcriptional level. Subsequent analysis will seek to examine whether IV-Iron produces beneficial effects on the translational & structural, components of skeletal muscle.