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
