Investigating the Role of Luminal Pressure on Arteriovenous Fistula Maturation

Arteriovenous Fistula Clinical Trial

Official title:

Study Protocol for a Prospective Observational Study Investigating the Role of Luminal Pressure on Arteriovenous Fistula Maturation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04017806
• Other study ID #: N201801091
• Status: Recruiting
• Start date: September 19, 2018
• Est. completion date: May 7, 2020

Study information

• Verified date: September 2018
• Source: Taipei Medical University WanFang Hospital
• Contact: Chung-te Liu, MD
• Phone: 886-970746583
• Email: 96320[@]wtmu.edu.tw
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Introduction Arteriovenous fistula (AVF) is the preferred hemodialysis vascular access due to its higher patency and lower infection rate. However, its major weakness is suboptimal maturation rate. Although that substantial risk factors for AVF maturation failure have been disclosed, a modifiable risk factor remains absent. While contemporary theory for AVF maturation failure focuses on disturbed wall shear stress, complicate assumtions and measurement preclude its clinical applicability. In the process of AVF maturation, elevated luminal pressure is required for outward remodeling, however, exccessively high luminal pressure may also be ditremental to AVF maturation, which remains to be defined. This study hypothesize that higher AVF luminal pressure is harmful to its maturation and investigate its potential as a modifiable factor to improve AVF maturation.

Methods and analysis This prospective study includes patients receiving surgical creation of native AVF. The exclusion criteria include age <20 years, inability to sign inform consent and failure to create native AVF deu to technical difficulty. Demographic and labboratory profile will be collected before AVF surgery. Vascular sonography will be performed within 1 week of AVF creation to measure the blood flow rates and diameters of AVF and its branched veins. The pressure gredient within AVF will be estimated from blood flow rates by Modified Bernoulli Equation. The primary outcome was spontaneous AVF maturation defined as provision of sufficient blood flow for hemodialysis within 2 months of its creation without any interventional procedures. The secondary outcome is assisted AVF mature, which is defined as AVF maturation within 2 months from its creation, which is aided by any interventional procedure before successful use of AVF.

Ethics and dissemination This study has been approved by the ethics committee and Institutional Review Board of Taipei Medical University.

Strengths and limitations

1. The strength of the present study is the prospective design that allows complete collection of parameters and outcomes.

2. The predictor of interest for AVF maturation is luminal pressure of AVF.

3. The study assesses hemodynamic parameters of AVF and its branched veins, including diameters, flow rates, and flow volume.

4. The luminal pressure of AVF will be estimated using Modified Bernoulli Equation.

5. The primary outcome of the study is spontaneous AVF maturation.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 7, 2020
• Est. primary completion date: May 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Patients with hemodialysis who receiving AVF.

2. AVF created at both radial and brachial arteries

Exclusion Criteria:

1. Patients at age <20 years old

2. Patients who are unconscious or unable to sign the inform consent

3. Patient in whom native AVF creation is shifted to arteriovenous graft placement

Related Conditions & MeSH terms

• Arteriovenous Fistula
• Fistula

Locations

Country	Name	City	State
Taiwan	Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Medical University WanFang Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (19)

Anker SD, Doehner W, Rauchhaus M, Sharma R, Francis D, Knosalla C, Davos CH, Cicoira M, Shamim W, Kemp M, Segal R, Osterziel KJ, Leyva F, Hetzer R, Ponikowski P, Coats AJ. Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging. Circulation. 2003 Apr 22;107(15):1991-7. Epub 2003 Apr 21. — View Citation

Bellomo G, Venanzi S, Verdura C, Saronio P, Esposito A, Timio M. Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis. 2010 Aug;56(2):264-72. doi: 10.1053/j.ajkd.2010.01.019. Epub 2010 Apr 10. — View Citation

Bo S, Cavallo-Perin P, Gentile L, Repetti E, Pagano G. Hypouricemia and hyperuricemia in type 2 diabetes: two different phenotypes. Eur J Clin Invest. 2001 Apr;31(4):318-21. — View Citation

Chonchol M, Shlipak MG, Katz R, Sarnak MJ, Newman AB, Siscovick DS, Kestenbaum B, Carney JK, Fried LF. Relationship of uric acid with progression of kidney disease. Am J Kidney Dis. 2007 Aug;50(2):239-47. — View Citation

Edvardsson VO, Kaiser BA, Polinsky MS, Palmer JA, Quien R, Baluarte HJ. Natural history and etiology of hyperuricemia following pediatric renal transplantation. Pediatr Nephrol. 1995 Feb;9(1):57-60. — View Citation

Goicoechea M, de Vinuesa SG, Verdalles U, Ruiz-Caro C, Ampuero J, Rincón A, Arroyo D, Luño J. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010 Aug;5(8):1388-93. doi: 10.2215/CJN.01580210. Epub 2010 Jun 10. — View Citation

Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med. 1984 Jan;76(1):47-56. — View Citation

Hsu SP, Pai MF, Peng YS, Chiang CK, Ho TI, Hung KY. Serum uric acid levels show a 'J-shaped' association with all-cause mortality in haemodialysis patients. Nephrol Dial Transplant. 2004 Feb;19(2):457-62. — View Citation

Iseki K, Oshiro S, Tozawa M, Iseki C, Ikemiya Y, Takishita S. Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res. 2001 Nov;24(6):691-7. — View Citation

Kamatani N, Fujimori S, Hada T, Hosoya T, Kohri K, Nakamura T, Ueda T, Yamamoto T, Yamanaka H, Matsuzawa Y. An allopurinol-controlled, multicenter, randomized, open-label, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 2 exploratory clinical study. J Clin Rheumatol. 2011 Jun;17(4 Suppl 2):S44-9. doi: 10.1097/RHU.0b013e31821d352f. Erratum in: J Clin Rheumatol. 2014 Sep;20(6):E3. Naoyuki, Kamatani [Kamatani, Naoyuki]; Shin, Fujimori [corrected to Fujimori, Shin]; Toshikazu, Hada [corrected to Hada, Toshikazu]; Tatsuo, Hosoya [corrected to Hosoya, Tatsuo]; Kenjiro, Kohri [corrected to Kohri, Kenjiro]; Toshitaka, Nakamura [corrected. — View Citation

Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M, Truong L, Harris R, Johnson RJ. A role for uric acid in the progression of renal disease. J Am Soc Nephrol. 2002 Dec;13(12):2888-97. — View Citation

Levy G, Cheetham TC. Is It Time to Start Treating Asymptomatic Hyperuricemia? Am J Kidney Dis. 2015 Dec;66(6):933-5. doi: 10.1053/j.ajkd.2015.09.002. — View Citation

Madero M, Sarnak MJ, Wang X, Greene T, Beck GJ, Kusek JW, Collins AJ, Levey AS, Menon V. Uric acid and long-term outcomes in CKD. Am J Kidney Dis. 2009 May;53(5):796-803. doi: 10.1053/j.ajkd.2008.12.021. Epub 2009 Mar 20. — View Citation

Sircar D, Chatterjee S, Waikhom R, Golay V, Raychaudhury A, Chatterjee S, Pandey R. Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia: A 6-Month, Double-Blind, Randomized, Placebo-Controlled Trial. Am J Kidney Dis. 2015 Dec;66(6):945-50. doi: 10.1053/j.ajkd.2015.05.017. Epub 2015 Jul 30. — View Citation

Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006 Jan;47(1):51-9. — View Citation

Sonoda H, Takase H, Dohi Y, Kimura G. Uric acid levels predict future development of chronic kidney disease. Am J Nephrol. 2011;33(4):352-7. doi: 10.1159/000326848. Epub 2011 Mar 25. — View Citation

Suliman ME, Johnson RJ, García-López E, Qureshi AR, Molinaei H, Carrero JJ, Heimbürger O, Bárány P, Axelsson J, Lindholm B, Stenvinkel P. J-shaped mortality relationship for uric acid in CKD. Am J Kidney Dis. 2006 Nov;48(5):761-71. — View Citation

Tanaka K, Nakayama M, Kanno M, Kimura H, Watanabe K, Tani Y, Hayashi Y, Asahi K, Terawaki H, Watanabe T. Renoprotective effects of febuxostat in hyperuricemic patients with chronic kidney disease: a parallel-group, randomized, controlled trial. Clin Exp Nephrol. 2015 Dec;19(6):1044-53. doi: 10.1007/s10157-015-1095-1. Epub 2015 Feb 13. — View Citation

Wang H, Wei Y, Kong X, Xu D. Effects of urate-lowering therapy in hyperuricemia on slowing the progression of renal function: a meta-analysis. J Ren Nutr. 2013 Sep;23(5):389-96. doi: 10.1053/j.jrn.2012.08.005. Epub 2012 Nov 4. Review. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome of this study is spontaneous AVF maturation.	Spontaneous AVF maturation, which is defined as successful AVF puncture in hemodialysis for 6 consecutive sessions without any interventional procedure within 2 months.	2 months
Secondary	The secondary outcome is assisted AVF mature.	Assisted AVF maturation, which is defined as successful AVF puncture in hemodialysis for 6 consecutive sessions with any interventional procedure within 2 months.	2 months