Exploratory Transcriptomic Profiling of Vein Tissue from Diabetic Patients Undergoing Arteriovenous Fistula Creation for Hemodialysis.
Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis; however, its patency is limited, particularly in patients with diabetes mellitus (DM). This study aimed to obtain exploratory data on whether changes in the venous transcriptome are present at the time of AVF creation in patients with DM and whether these changes are related to the graft prognosis.
We conducted prospective transcriptome analyses using venous samples obtained during AVF creation from 22 patients (12 with DM and 10 without DM). RNA sequencing was performed, and clinical outcomes, including primary patency, were tracked for one year.
AVF patency was significantly lower in the DM group (median patency: 134 vs. 365 days, p＜0.05). Transcriptome profiling identified 285 differentially expressed genes, including those related to extracellular matrix organization, mitochondrial electron transport, TGF-β signaling, and the unfolded protein response. A network analysis highlighted hub genes, including MRPL27, MRPL23, and MRPL1, as potential biomarkers. A Cox regression analysis identified genes associated with the AVF prognosis, including PER3, SERINC2, COMMD10, TTC4, FKBP2, FN3KRP, KIF24, SNX32, MOB3C, SUV39H1, and TIGD6. Notably, a high COMMD10 expression, a core component of the commander complex, was associated with a shortened patency in patients with DM.
Our findings demonstrate that DM is associated with distinct transcriptomic alterations in the access veins at the time of AVF creation. This integrative approach provides novel insights into the molecular basis of DM-related AVF failure and the potential to identify novel therapeutic targets.
We conducted prospective transcriptome analyses using venous samples obtained during AVF creation from 22 patients (12 with DM and 10 without DM). RNA sequencing was performed, and clinical outcomes, including primary patency, were tracked for one year.
AVF patency was significantly lower in the DM group (median patency: 134 vs. 365 days, p＜0.05). Transcriptome profiling identified 285 differentially expressed genes, including those related to extracellular matrix organization, mitochondrial electron transport, TGF-β signaling, and the unfolded protein response. A network analysis highlighted hub genes, including MRPL27, MRPL23, and MRPL1, as potential biomarkers. A Cox regression analysis identified genes associated with the AVF prognosis, including PER3, SERINC2, COMMD10, TTC4, FKBP2, FN3KRP, KIF24, SNX32, MOB3C, SUV39H1, and TIGD6. Notably, a high COMMD10 expression, a core component of the commander complex, was associated with a shortened patency in patients with DM.
Our findings demonstrate that DM is associated with distinct transcriptomic alterations in the access veins at the time of AVF creation. This integrative approach provides novel insights into the molecular basis of DM-related AVF failure and the potential to identify novel therapeutic targets.
Authors
Shirouzu Shirouzu, Koga Koga, Katafuchi Katafuchi, Nagai Nagai, Suga Suga, Sanada Sanada, Ueno Ueno, Nakazono Nakazono, Hasegawa Hasegawa, Miyamoto Miyamoto, Nakayama Nakayama, Kataoka Kataoka
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