Bioinformatics Identifies Predictors of Arteriovenous Fistula Maturation

Overview

Journal J Vasc Access

Publisher Sage Publications

Date 2022 Jun 10

PMID 35686495

Authors

Jia Liu

Dingyao Zhang

Anand Brahmandam

Yutaka Matsubara

Mingjie Gao

Jingru Tian

Bing Liu

Chang Shu

Alan Dardik

Affiliations

Soon will be listed here.

Abstract

Background: Arteriovenous fistulae (AVF) are the preferred access for hemodialysis but still have poor rates of maturation and patency limiting their clinical use. The underlying mechanisms of venous remodeling remain poorly understood, and only limited numbers of unbiased approaches have been reported.

Methods: Biological Gene Ontology (GO) term enrichment analysis and differentially expressed genes (DEG) analysis were performed for three AVF datasets. A microRNA enrichment analysis and L1000CDS query were performed to identify factors predicting AVF patency.

Results: The inflammatory and immune responses were activated during both early and late phases of AVF maturation, with upregulation of neutrophil and leukocyte regulation, cytokine production, and cytokine-mediated signaling. In men with failed AVF, negative regulation of myeloid-leukocyte differentiation and regulation of macrophage activation were significantly upregulated. Compared to non-diabetic patients, diabetic patients had significantly reduced immune response-related enrichment such as cell activation in immune response, regulation of immune-effector process, and positive regulation of defense response; in addition, diabetic patients showed no enrichment of the immune response-regulating signaling pathway.

Conclusions: These data show coordinated, and differential regulation of genes associated with AVF maturation, and different patterns of several pathways are associated with sex differences in AVF failure. Inflammatory and immune responses are activated during AVF maturation and diabetes may impair AVF maturation by altering these responses. These findings suggest several novel molecular targets to improve sex specific AVF maturation.

Citing Articles

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References

Levula M, Oksala N, Airla N, Zeitlin R, Salenius J, Jarvinen O . Genes involved in systemic and arterial bed dependent atherosclerosis--Tampere Vascular study. PLoS One. 2012; 7(4):e33787. PMC: 3324479. DOI: 10.1371/journal.pone.0033787. View

Yan Y, Ye D, Yang L, Ye W, Zhan D, Zhang L . A meta-analysis of the association between diabetic patients and AVF failure in dialysis. Ren Fail. 2018; 40(1):379-383. PMC: 6014481. DOI: 10.1080/0886022X.2018.1456464. View

Edgar R, Domrachev M, Lash A . Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2001; 30(1):207-10. PMC: 99122. DOI: 10.1093/nar/30.1.207. View

Han H, Hahn S, Jeong H, Jee J, Nam M, Kim H . LINCS L1000 dataset-based repositioning of CGP-60474 as a highly potent anti-endotoxemic agent. Sci Rep. 2018; 8(1):14969. PMC: 6175892. DOI: 10.1038/s41598-018-33039-0. View

Miller P, Tolwani A, Luscy C, Deierhoi M, Bailey R, Redden D . Predictors of adequacy of arteriovenous fistulas in hemodialysis patients. Kidney Int. 1999; 56(1):275-80. DOI: 10.1046/j.1523-1755.1999.00515.x. View

Sung S, Ko G, Jo S, Cho W, Kim H, Lee S . Interleukin-10 and tumor necrosis factor-alpha polymorphisms in vascular access failure in patients on hemodialysis: preliminary data in Korea. J Korean Med Sci. 2008; 23(1):89-93. PMC: 2526491. DOI: 10.3346/jkms.2008.23.1.89. View

Lok C, Huber T, Lee T, Shenoy S, Yevzlin A, Abreo K . KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update. Am J Kidney Dis. 2020; 75(4 Suppl 2):S1-S164. DOI: 10.1053/j.ajkd.2019.12.001. View

Barhoumi T, Kasal D, Li M, Shbat L, Laurant P, Neves M . T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension. 2011; 57(3):469-76. DOI: 10.1161/HYPERTENSIONAHA.110.162941. View

Allon M . Current management of vascular access. Clin J Am Soc Nephrol. 2007; 2(4):786-800. DOI: 10.2215/CJN.00860207. View

10.

Cui J, Kessinger C, Jhajj H, Grau M, Misra S, Libby P . Atorvastatin Reduces Fibrin Deposition and Macrophage Accumulation, and Improves Primary Patency Duration and Maturation of Murine Arteriovenous Fistula. J Am Soc Nephrol. 2020; 31(5):931-945. PMC: 7217409. DOI: 10.1681/ASN.2019060612. View

11.

Owens C, Wake N, Kim J, Hentschel D, Conte M, Schanzer A . Endothelial function predicts positive arterial-venous fistula remodeling in subjects with stage IV and V chronic kidney disease. J Vasc Access. 2010; 11(4):329-34. PMC: 3164886. DOI: 10.5301/jva.2010.5833. View

12.

Nath K, OBrien D, Croatt A, Grande J, Ackerman A, Nath M . The murine dialysis fistula model exhibits a senescence phenotype: pathobiological mechanisms and therapeutic potential. Am J Physiol Renal Physiol. 2018; 315(5):F1493-F1499. PMC: 6293292. DOI: 10.1152/ajprenal.00308.2018. View

13.

Martinez L, Tabbara M, Duque J, Selman G, Santos Falcon N, Paez A . Transcriptomics of Human Arteriovenous Fistula Failure: Genes Associated With Nonmaturation. Am J Kidney Dis. 2019; 74(1):73-81. PMC: 10980359. DOI: 10.1053/j.ajkd.2018.12.035. View

14.

Kasal D, Barhoumi T, Li M, Yamamoto N, Zdanovich E, Rehman A . T regulatory lymphocytes prevent aldosterone-induced vascular injury. Hypertension. 2011; 59(2):324-30. DOI: 10.1161/HYPERTENSIONAHA.111.181123. View

15.

Allon M, Robbin M . Increasing arteriovenous fistulas in hemodialysis patients: problems and solutions. Kidney Int. 2002; 62(4):1109-24. DOI: 10.1111/j.1523-1755.2002.kid551.x. View

16.

Kuwahara G, Hashimoto T, Tsuneki M, Yamamoto K, Assi R, Foster T . CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation. Arterioscler Thromb Vasc Biol. 2017; 37(6):1147-1156. PMC: 5467640. DOI: 10.1161/ATVBAHA.117.309385. View

17.

Shu C, Benoist C, Mathis D . The immune system's involvement in obesity-driven type 2 diabetes. Semin Immunol. 2013; 24(6):436-42. PMC: 3582811. DOI: 10.1016/j.smim.2012.12.001. View

18.

Tan A, Swain S . Review of flavopiridol, a cyclin-dependent kinase inhibitor, as breast cancer therapy. Semin Oncol. 2002; 29(3 Suppl 11):77-85. DOI: 10.1053/sonc.2002.34059. View

19.

Cai C, Kilari S, Singh A, Zhao C, Simeon M, Misra A . Differences in Transforming Growth Factor-β1/BMP7 Signaling and Venous Fibrosis Contribute to Female Sex Differences in Arteriovenous Fistulas. J Am Heart Assoc. 2020; 9(16):e017420. PMC: 7660821. DOI: 10.1161/JAHA.120.017420. View

20.

Lontchi-Yimagou E, Sobngwi E, Matsha T, Kengne A . Diabetes mellitus and inflammation. Curr Diab Rep. 2013; 13(3):435-44. DOI: 10.1007/s11892-013-0375-y. View