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Kidney Week

Abstract: SA-PO979

Chemerin/ChemR23 Axis: A New Therapeutic Target for Uraemic Sarcopenia

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Baker, Luke A., University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
  • Wilkinson, Thomas James, University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
  • Abbott, Milly, University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
  • Cardoso, Daniela Filipa, Instituto Universitario da Maia, Castelo da Maia, Porto, Portugal
  • Parker, Nicola, University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
  • Graham-Brown, Matthew, University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
  • Viana, Joao L., Instituto Universitario da Maia, Castelo da Maia, Porto, Portugal
  • Watson, Emma L., University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
  • Smith, Alice C., University of Leicester College of Life Sciences, Leicester, East Midlands, United Kingdom
Background

People with chronic kidney disease (CKD) often experience muscle quality, wasting and dysfunction contributing to a reduced quality of life and increased risk of morbidity and mortality. The adipokine chemerin is associated with CKD progression and involved in inflammatory-related signalling processes. With chronic inflammation recognised as a key factor in uraemic sarcopenia, we aimed to investigate the potential role of chemerin as a uraemic toxin in CKD and identify the mechanisms of action to elucidate therapeutic opportunities in uraemic sarcopenia.

Methods

Chemerin levels from EDTA-plasma and urine samples were quantified via ELISA on basal samples from non-CKD controls (CON, n=32), CKD patients (CKD, n=100), and kidney transplant recipients (KTR, n=20). Chemerin levels were correlated with eGFR and measures of body composition, physical performance, muscle mass, and muscle quality. A sub-set of participants from each group underwent skeletal muscle biopsies and samples were processed for gene and protein analysis, or cells extracted for in-vitro experimentation.

Results

Higher chemerin concentrations were found in the urine of those with CKD compared to non-CKD controls (p<0.001). Higher circulating chemerin was associated with lower eGFR (p<0.001, r=-0.571). Positive correlations with body fat % and BMI were noted in CKD patients. Higher circulatory chemerin was associated with poorer muscle quality (r=0.396, p=0.003). No associations were noted across other in-vivo muscle related assessments. Molecular analysis detected the presence of 2 out of 3 receptors of interest for chemerin in skeletal muscle, but no significant elevation in the expression in of chemerin itself in this tissue type in those with CKD. In-vitro analysis showed that the exposure of CKD derived muscle cells to chemerin induced a significant inflammatory response (IL-6 p<0.001; TNFa p=0.0215), which was halved using the ChemR23 receptor inhibitor aNETA (IL-6 p<0.001; TNFa p<0.001).

Conclusion

We report that chemerin is a uraemic toxin in those with CKD and that it may contribute to poorer muscle quality in these people. Chemerin can moderate indicators of inflammation within skeletal muscle via the activation of ChemR23 and as such proposes a new therapeutic target to alleviate the symptoms of uraemic sarcopenia.