Seq-ing the Truth: Baseline snRNA-Seq Links Endothelial Interferon/TNF-NFκB Signalling and Smooth Muscle Bioenergetic Suppression to Arteriovenous Fistula Maturation.

Authors

Nasir A Shah, Renu Thomas, Shannon D Thomas, Amy Y M Au, Trent Davidson, Christopher J O'Keeffe, Orion Tong, Zoltan H Endre, Tracie J Barber, Blake J Cochran, Jonathan H Erlich

Published in

Kidney360. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Arteriovenous fistula (AVF) non-maturation remains common. Although attention has historically focused on post-operative processes, evidence suggests that pre-anastomotic vessel wall signaling, at AVF creation, contributes to subsequent AVF outcomes. To integrate quantitative baseline biochemistry, and vein histology with single-nucleus RNA sequencing (snRNA-seq) from intraoperative tissue and relate structural, cellular, and molecular features to subsequent AVF maturation.
In a prospective single-centre observational cohort, 17 consecutive patients undergoing first AVF creation contributed venous tissue for snRNA-seq. Maturation was adjudicated using clinical and/or ultrasound criteria. snRNA-seq used donor-level pseudobulk differential expression within annotated cell types with pre-ranked Hallmark pathway enrichment; serum IL-6 (where available) was included.
Nine AVFs matured and eight failed to mature. Histologic intima-media thickness did not differ by outcome. An intact endothelial layer was more frequent in matured AVFs but did not reach significance (78% vs 25%; P=0.06). Serum IL-6 did not differ (P=0.69). Brachial artery flow at assessment was markedly higher in matured AVFs (mean 973 vs 146 mL/min; p<0.001). Endothelial cells from failed-to-mature AVFs showed strong enrichment of interferon-α/γ responses and TNFα/NF-κB signalling (FDR<0.001), with additional enrichment of mTORC1 and MYC targets. In vascular smooth muscle cells, failed-to-mature AVFs showed depletion of oxidative phosphorylation, MYC/E2F targets, and translation/ribosome programs, alongside enrichment of TNFα/NF-κB signalling.
Baseline vessel-wall transcriptomes were associated with endothelial inflammatory priming and reduced vascular smooth muscle bioenergetic/proliferative programs in AVFs that subsequently failed to mature. This may inform early risk stratification.

PMID:
42467961
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.

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