Once they mature, dialysis fistulas have longer survival and require fewer interventions to maintain long-term patency for dialysis, as compared with grafts. However, 20-60% of new fistulas fail to mature adequately to be suitable for dialysis. Preoperative vascular mapping is widely promoted to identify vessels suitable for fistula creation, by setting minimum vascular diameters and ensuring vessel patency. Although vascular mapping increases fistula placement, it does not decrease fistula non- maturation. This disappointing outcome suggests the existence of additional vascular properties affecting fistula immaturity, which are not measured by standard preoperative mapping. During a 3- month pilot study, we obtained arterial specimens from 23 patients undergoing fistula creation. Severe medial fibrosis was present in 65% (15/23) of the arteries. In 14 patients with >6 months of follow-up, fistula non-maturation occurred in 50% (5/10) of patients with medial fibrosis vs. 0% (0/4) of those without medial fibrosis. Medial fibrosis may limit arterial dilation after fistula creation. Endothelial heme oxygenase-1 (HO-1) expression was decreased in arteries with medial fibrosis, as compared to arteries without medial fibrosis, providing a potential mechanism for impaired vasodilation. Our hypothesis is that preexisting arterial medial fibrosis, which can be identified by vascular histology or by duplex ultrasound, is a strong predictor of fistula non-maturation in CKD patients. This grant proposes to measure preoperative arterial medial fibrosis in CKD patients receiving a fistula, and correlate it with fistula non-maturation. Specifically, we will:
Aim 1 : Determine whether preexisting medial fibrosis in the artery used to create a fistula is predictive of fistula non-maturation.
Aim 2 : Evaluate whether increased arterial intima-media thickness (IMT) and decreased flow- mediated dilation on preoperative ultrasound are surrogate markers of medial fibrosis.
Aim 3 : Determine whether fistula non-maturation is associated with altered expression of vasoactive substances, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-2), and heme oxygenase-1 (HO-1). To achieve the specific aims, a multidisciplinary team has been assembled, consisting of nephrology, radiology, surgery, and pathology. Planned studies will: (1) measure the IMT and flow-mediated dilation of the arteries during preoperative ultrasound mapping;(2) score vessel characteristics clinically at the time of surgery;(3) grade histologically medial fibrosis in the artery used to create the fistula;(4) score vascular expression of PDGF, TGF-2, and HO-1;(5) measure fistula blood flow postoperatively by ultrasound;and (6) determine fistula suitability for dialysis (clinical maturation).

Public Health Relevance

Fistulas are created surgically in dialysis patients to provide a way to purify blood during dialysis treatments. Unfortunately, about 50% of fistulas don't mature, and therefore cannot be used for dialysis. The goal of this study is to identify abnormalities of the arteries and veins that predict whether a fistula will mature.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK085027-03
Application #
8296317
Study Section
Special Emphasis Panel (ZRG1-DKUS-B (03))
Program Officer
Kimmel, Paul
Project Start
2010-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$349,511
Indirect Cost
$110,937
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Feng, Wenguang; Chumley, Phillip; Allon, Michael et al. (2014) The transcription factor E26 transformation-specific sequence-1 mediates neointima formation in arteriovenous fistula. J Am Soc Nephrol 25:475-87
Allon, Michael; Robbin, Michelle L; Young, Carlton J et al. (2013) Preoperative venous intimal hyperplasia, postoperative arteriovenous fistula stenosis, and clinical fistula outcomes. Clin J Am Soc Nephrol 8:1750-5
Allon, Michael; Zhang, Li; Maya, Ivan D et al. (2012) Association of factor V gene polymorphism with arteriovenous graft failure. Am J Kidney Dis 59:682-8
Allon, Michael; Litovsky, Silvio; Young, Carlton J et al. (2011) Medial fibrosis, vascular calcification, intimal hyperplasia, and arteriovenous fistula maturation. Am J Kidney Dis 58:437-43