ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO616

Circulating Small Non-Coding RNA Profiles for Premature Cardiovascular Death in Hemodialysis Patients

Session Information

Category: Hypertension and CVD

  • 1501 Hypertension and CVD: Epidemiology‚ Risk Factors‚ and Prevention

Authors

  • Sumida, Keiichi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Naik, Surabhi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Han, Zhongji, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Mallisetty, Yamini, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Kuscu, Cem, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Kovesdy, Csaba P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Kuscu, Canan, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
Background

Patients with ESKD suffer from disproportionately high cardiovascular disease (CVD) burden. Circulating small non-coding RNAs (c-sncRNAs) have emerged as novel epigenetic regulators and are suggested as novel biomarkers and therapeutic targets for CVD; however, little is known about the associations of c-sncRNAs with premature CV death in ESKD.

Methods

Using plasma samples of 50 hemodialysis (HD) patients who died of CV events (cases) and of 50 HD controls who remained alive during a median follow-up of 2.0 years, matched by age, sex, race, and dialysis vintage, we performed c-sncRNAs profile using next-generation sequencing to identify differentially expressed microRNAs (miRNAs) between cases and controls. The association of differentially expressed miRNAs with CV mortality were examined using multivariable conditional logistic regression.

Results

Patient characteristics were similar between cases and controls, with a mean age of 63 years, 48% male, and 54% African American in both groups. Among 613 miRNAs detected in the plasma, five miRNAs (i.e., miR-129-1-5p, miR-500b-3p, miR-125b-1-3p, miR-3648-2-5p, and miR-3150b-3p) were identified to be significantly differentially expressed between cases and controls with cut-offs of p <0.01 and log2 fold-change (log2FC) >1. When using more stringent cut-offs of p-adjusted <0.05 and log2FC >1, only miR-129-1-5p, which is involved in oxidative stress, inflammation, and cardiovascular pathophysiology, remained significant with higher levels of miR-129-1-5p in cases than in controls (Figure A). The expression levels of miR-129-1-5p were significantly associated with risk of CV death (adjusted ORs [95%CI], 1.03 [1.00-1.06] for 1 increase in DESeq2 normalized counts), independent of matched variables, diabetes, history of CVD, and serum albumin and phosphorus levels (Figure B).

Conclusion

Circulating miR-129-1-5p may serve as a novel biomarker for premature CV death in ESKD.

(A) MiR129-1-5p normalized counts in plasma of cases and controls; and (B) Odds ratios and 95% confidence interval for cardiovascular death associated with circulating miR-129-1-5p