TY - JOUR
T1 - Fibrotic venous remodeling and nonmaturation of arteriovenous fistulas
AU - Martinez, Laisel
AU - Duque, Juan C.
AU - Tabbara, Marwan
AU - Paez, Angela
AU - Selman, Guillermo
AU - Hernandez, Diana R.
AU - Sundberg, Chad A.
AU - Sheng Tey, Jason Chieh
AU - Shiu, Yan Ting
AU - Cheung, Alfred K.
AU - Allon, Michael
AU - Velazquez, Omaida C.
AU - Salman, Loay H.
AU - Vazquez-Padron, Roberto I.
N1 - Funding Information:
This study was supported by the National Institutes of Health (NIH) grantR01DK098511toL.H.S.andR.I.V.-P.,andR01DK100505toY.-T.S. We also acknowledge the statistical assistance by the University of Utah Study Design and Biostatistics Center, with funding, in part, from the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH grant 8UL1TR000105 (formerly NIH grant UL1RR025764). Second harmonic generation microscopy imaging was performed at the Cell Imaging Core Facility, a part of the Health Sciences Cores at the University of Utah. Microscopy equipment was obtained using the National Center for Research Resources Shared Equipment grant 1S10RR024761-01.
Funding Information:
This study was supported by the National Institutes of Health (NIH) grant R01DK098511 to L.H.S. and R.I.V.-P., and R01DK100505 to Y.-T.S. We also acknowledge the statistical assistance by the University of Utah Study Design and Biostatistics Center, with funding, in part, from the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH grant 8UL1TR000105 (formerly NIH grant UL1RR025764). Second harmonic generation microscopy imaging was performed at the Cell Imaging Core Facility, a part of the Health Sciences Cores at the University of Utah. Microscopy equipment was obtained using the National Center for Research Resources Shared Equipment grant 1S10RR024761-01.
Publisher Copyright:
Copyright © 2018 by the American Society of Nephrology.
PY - 2018/3
Y1 - 2018/3
N2 - The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR],1.55; 95% confidence interval [95%CI],1.05 to 2.30;P=0.03, per 10% absolute increase infibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population's median value (OR, 2.63; 95% CI, 1.07 to 6.46; P=0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95%CI, 1.03 to 1.84; P=0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.
AB - The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR],1.55; 95% confidence interval [95%CI],1.05 to 2.30;P=0.03, per 10% absolute increase infibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population's median value (OR, 2.63; 95% CI, 1.07 to 6.46; P=0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95%CI, 1.03 to 1.84; P=0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.
UR - http://www.scopus.com/inward/record.url?scp=85042721951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042721951&partnerID=8YFLogxK
U2 - 10.1681/ASN.2017050559
DO - 10.1681/ASN.2017050559
M3 - Article
C2 - 29295872
AN - SCOPUS:85042721951
VL - 29
SP - 1030
EP - 1040
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
SN - 1046-6673
IS - 3
ER -