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Thromb Haemost
DOI: 10.1055/a-2413-2792
Stroke, Systemic or Venous Thromboembolism

Transfer RNAs are Linked to Ischemic Stroke and Major Bleeding in Patients with End-Stage Kidney Disease

Stephan Nopp
1   Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
,
Oliver Königsbrügge
1   Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
,
Sabine Schmaldienst
2   Department of Medicine I, Clinic Favoriten, Vienna, Austria
,
Marcus Säemann
3   Department of Medicine VI, Clinic Ottakring, Vienna, Austria
,
Ingrid Pabinger
1   Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
,
Anne Yaël Nossent   *
4   Department for Nutrition, Exercise and Sports (NEXS), University of Copenhagen, Copenhagen, Denmark
,
Cihan Ay   *
1   Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
› Institutsangaben Funding The VIVALDI study was supported by an unrestricted grant from the Austrian National Bank (Jubiläumsfond Österreichische Nationalbank, Project Number 16433), Joseph-Skoda-Prize of the Austrian Association of Internal Medicine (ÖGIM), and the Austrian Science Fund (FWF), Special Research Program (SFB) 54.
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Abstract

Background Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small noncoding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population.

Methods In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case–control studies, each comprising 18 participants. The primary outcomes were ischemic stroke in the first study and major bleeding in the second. Plasma samples were processed using the miND pipeline for RNA-seq analysis to investigate differential expression of microRNAs and tRNA/tRFs between cases and their respective matched controls, with results stringently adjusted for the false discovery rate (FDR).

Results No significant differential expression of microRNAs for either ischemic stroke or major bleeding outcomes was observed in the two nested case–control studies. However, we identified four tRNAs significantly differentially expressed in ischemic stroke cases and seven in major bleeding cases, compared with controls (FDR < 0.1). Coverage plots indicated that specific tRNA fragments (tRFs), rather than full-length tRNAs, were detected, however. Alternative mapping approaches revealed challenges and technical limitations that precluded in-depth differential expression analyses on these specific tRFs. Yet, they also underscored the potential of tRNAs and tRFs as markers for thromboembolism and bleeding.

Conclusion While microRNAs did not show significant differential expression, our study identifies specific tRNAs/tRFs as potential novel biomarkers for ischemic stroke and major bleeding in ESKD patients.

Keywords

microRNAs - kidney diseases - thromboembolism - hemostasis - biomarkers - tRNAs - RNA-seq analysis

Data Availability Statement

The RNA-Seq data will be deposited in NCBI Gene Expression Omnibus data repository with the accession number GSE272125. The data are freely available.


Authors' Contribution

Concept and design: O.K., S.N., I.P., M.S., A.Y.N., C.A.; acquisition, analysis, or interpretation of data: S.N., O.K., I.P., A.Y.N., C.A.; drafting of the manuscript: S.N.; critical revision of the manuscript for important intellectual content: all authors; statistical analysis: S.N.; administrative, technical, or material support: S.S., M.S., I.P., A.Y.N., C.A.; supervision: A.Y.N., C.A.


* These authors contributed equally as senior authors.


Supplementary Material



Publikationsverlauf

Eingereicht: 23. Mai 2024

Angenommen: 09. September 2024

Accepted Manuscript online:
11. September 2024

Artikel online veröffentlicht:
03. Oktober 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 

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