Background: AVF is the preferred vascular access for maintenance hemodialysis. However, AVF is not an ideal vascular access without any drawback. Previous studies had revealed several risk factors of AVF maturation failure, including anemia, diabetes mellitus, and smoking. On the other hand, basic studies have revealed molecular pathogenic factors of AVF maturation failure, including localized inflammation, hypoxic injury, oscillating wall shear stress, uremic milieu and oxidative stress. Despite of these substantial studies exploring the role of pathogenic factors, a modifiable pathogenic factor that is applicable to improve AVF maturation remains lacking.

Maturation failure of AVF results from luminal stenosis due to neointimal hyperplasia, signifying thickening of subintimal area caused by proliferation of myofibroblast, which is remarkably stained for α-smooth muscle actin and vimentin. Neointimal hyperplasia of AVF occurs mainly at the arteriovenous junction and venous limb of AVF, where venous endothelium is exposed to non-physiologically high blood flow rate, oscillatory shear stress and pulsatile stretching strain by arterial blood flow, suggesting the role of altered hemodynamics on AVF subintimal proliferation. It has also been reported that endothelial cells from arterial and venous parts of circulation system show different genetic expression, indicating that different hemodynamic environment regulates phenotypes of endothelial cells. Therefore, it is reasonable that elevated luminal pressure may stimulate proliferation in venous endothelium of AVF and result in maturation failure. In contrast, elevated AVF luminal pressure also provides stretching force for outward remodeling, which is required for AVF maturation. Therefore, this prospective observational study is conducted to investigate the optimal AVF luminal pressure for AVF maturation, which may be modified surgically or pharmaceutically to improve AVF maturation rate.

Specific aims Aim 1: To characterize the altered blood flow rates and luminal pressures in different segments of AVF. Aim 2: To characterize the association between luminal pressures and vessel diameters of different segments of AVF. Aim 3: To investigate the association between AVF luminal pressure and AVF maturation rate. Aim 4: To investigate the association between AVF luminal pressure and known risk factors of AVF maturation failure.

Methods and analysis: This prospective observational study is mainly aimed to investigate the association between AVF luminal pressure and maturation rate. Patients who meet the following eligibility criteria are eligible for enrollment: (1) Patient at pre-dialysis or post-dialysis status who undergoes surgical creation of native AVF for hemodialysis will be included. (2) AVF created at both radial and brachial arteries are eligible for inclusion. Exclusion criteria: (1) Patients at age \<20 years old will be excluded (2) Patients who are unconscious or unable to sign the inform consent will be excluded (3) Patient in whom native AVF creation is shifted to arteriovenous graft placement due to technical difficulty will be excluded from this study. The recruit of participants, collection of parameters, and confirmation of the outcomes are performed by a full-time study nurse.

Statistic methods: Continuous variables will be expressed as mean ± standard deviation, while nominal variables are expressed in frequency and percentage. Comparisons of continuous variables will be performed using the two-tailed t-test for unpaired samples or Welch's t-test as appropriate. Comparisons of nominal variables will be performed using the Chi-square test or Fisher's exact test as appropriate. Multivariate logistic regression test will be used to evaluate the association between predictor variables and outcome variables. Statistical significance will be defined by a P value of \<0.05. The statistics will be performed using SAS 9.4 (SAS Institute Inc, Cary, NC, USA). G\*Power 3.1.9.4 was used to estimate the sample size to reach statistical significance in the t-test. Assuming the effect size to be 0.6. Under the condition that α error is defined as 0.05; power was defined as 0.8; and the allocation ratio was defined as 1. Therefore, the sample size required to achieve statistical significance is 90 patients. The data used for the study will be preserved and analyzed by the primary investigator. The data is accessible only to the primary investigator and study nurse for data safety. The data will be preserved for 2 years after the end of the study.