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Please note that you are viewing an archived section from 2019 and some content may be unavailable. To unlock all content for 2019, please visit the archives.

Abstract: SA-PO770

Discovery and Validation of Skeletal Muscle MicroRNA Expression in Non-Dialysis CKD

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

  • Robinson, Kate A., University of Leicester, Leicester, United Kingdom
  • Baker, Luke A., University of Leicester, Leicester, United Kingdom
  • Graham-Brown, Matthew P.M., University of Leicester, Leicester, United Kingdom
  • Ashford, Robert U., University of Leicester, Leicester, United Kingdom
  • Watson, Emma L., University of Leicester, Leicester, United Kingdom
Background

Skeletal muscle (SM) wasting is a common complication of chronic kidney disease (CKD), and is significantly associated with an increased risk of morbidity and mortality. The precise mechanisms of SM wasting are not fully defined, but multiple studies have identified a major contribution of aberrant microRNA (miR) expression and regulation. The involvement of miRs has been described in animal models of CKD SM wasting, however there is no evidence for their involvement in human CKD SM wasting. Therefore, we investigated SM miR expression in non-dialysis CKD patients compared to matched healthy controls (HCs).

Methods

Next Generation Sequencing (NGS) was performed on lower limb (LL) SM biopsies collected from 5 CKD patients stage 3b-5 (mean eGFR 22.0 ± 8.1 ml/min/1.73m2; mean age 59.2 ± 9.4 years) and 5 HCs (mean age 54.7 ± 7.9 years). MiR expression was then validated in LL SM biopsies collected from a further 10 CKD patients stage 3a-5 (mean eGFR 30.8 ± 13.6 ml/min/1.73m2; mean age 61.6 ± 11.8 years) and 10 HCs (mean eGFR 83.2 ± 4.4 ml/min/1.73m2; mean age 61.5 ± 13.4 years) by qPCR with let-7f as an internal control. Relative expression was calculated by 2-DCT).

Results

NGS identified differential expression of 15 miRs in SM of CKD patients compared to HCs (fold-change ≥1.5; increased: miR-128, 148a, 182, 21, 22, 29c, 92a; decreased: let-7a, 7e, miR-100, 191, 206, 486, 99a, 99b). Upon validation in a larger sample, miR-148a expression was significantly decreased in CKD patients compared to HCs (p=0.03), and there was a non-significant trend towards decreased miR-191 expression in CKD patients (p=0.061). No further differences were maintained upon validation of the other miRs.

Conclusion

Patients with non-dialysis CKD exhibit altered SM miR expression compared to HCs. However, the miR signature reported here does not reflect those previously reported in animal models of CKD SM wasting. For the first time, we report that miR-148a expression is significantly decreased in SM in CKD. Future work will explore the role of dysregulated miR-148a in CKD SM wasting, thus providing a rational for use as a potential therapeutic target in this population.