Kidney Week

Abstract: SA-PO769

Phenotype or Environment: Mechanisms of CKD Skeletal Muscle Wasting

Session Information

• CKD: Mechanisms - III
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2103 CKD (Non-Dialysis): Mechanisms

Authors

• O'Sullivan, Tom, University of Leicester, Leicester General Hospital, United Kingdom

Tom O'Sullivan,

• Baker, Luke A., University of Leicester, Leicester General Hospital, United Kingdom

Luke A. Baker,

• Smith, Alice C., University of Leicester, Leicester General Hospital, United Kingdom

Alice C. Smith,

• Watson, Emma L., University of Leicester, Leicester General Hospital, United Kingdom

Emma L. Watson,

Group or Team Name

• Leicester Kidney Lifestyle Team

Background

Despite its prevalence and impact, mechanisms of skeletal muscle wasting in non-dialysis dependent chronic kidney disease (NDD-CKD) are unclear. The current investigation used human primary skeletal muscle cells (HDMCs) to investigate the effect of CKD derived serum on HDMC proliferation and differentiation in-vitro.

Methods

Biopsies were taken from the vastus lateralis of NDD-CKD (n=3, 45.3yrs, eGFR 16ml.min.1.73m²) and healthy controls (HC, n=3, 48.3yrs, eGFR>90 ml.min.1.73m²). Isolated HDMCs were cultured for 4 days in medium supplemented with foetal bovine serum (FBS, 20%), HC (sHC) or CKD (sCKD) derived serum (10%). Proliferation was assessed using AlamarBlue^TM assay. To assess differentiation, cells were grown to confluence in FBS, followed by 7 days in either 2% horse serum (HS), sHC or sCKD and myotube morphology was analysed.

Results

Proliferation increased significantly from baseline in all conditions in HC and CKD. There was a significant effect of sera in HC, with greater proliferation in sCKD from D2 compared to FBS and D3 compared to sHC (Fig.1a). There was no effect of sera on CKD proliferation (Fig.1b).
Fusion index (Fig.1c) and myotube diameter (Fig.1e) was generally higher in CKD, but only significantly in sHC and HS, respectively. There was no significant effect of sera on either outcome. There was no effect of donor or sera on desmin index (Fig.1d).

Conclusion

Preliminary findings indicate similar rates of proliferation between HC and CKD. sCKD increased proliferation compared to FBS and sHC in HC but not CKD. There was no effect of sera on measures of differentiation/maturation. Future work will seek to determine what factors increase HDMC proliferation which may inform targets for therapeutic intervention.

Figure 1. The effect of sCKD on proliferation in HC (a) and CKD (b) and differentiation (c-e).

Funding

• Government Support - Non-U.S.