Abstract: FR-PO709
Role of Mevalonate Pathway on Vascular Access Failure in Maintenance Hemodialysis
Session Information
- Dialysis: Vascular Access - I
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 704 Dialysis: Vascular Access
Authors
- Kanda, Manabu, Japan Community Health Care Organization Sendai Hospital, Sendai, Japan
- Sanada, Satoru, Japan Community Health Care Organization Sendai Hospital, Sendai, Japan
- Sato, Mitsuhiro, Japan Community Health Care Organization Sendai Hospital, Sendai, Japan
- Sato, Toshinobu, Japan Community Health Care Organization Sendai Hospital, Sendai, Japan
- Taguma, Yoshio, Japan Community Health Care Organization Sendai Hospital, Sendai, Japan
Background
We have reported the effectiveness of statins against vascular access (VA) dysfunction. Despite statin administration, there was no difference in serum cholesterol levels between the statin users and the non-users, suggesting that the VA protective role of statin is different from the cholesterol lowering effect.
In recent years, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) were found as a new pathway associated with arteriosclerosis. The turbulence of intravascular blood flow triggers the YAP/TAZ pathway, which enhances gene expressions correlated with inflammation and fibrosis, resulting in arteriosclerosis. Mevalonate acid (MA) activates this pathway and statins are known to inhibit the MA production. Therefore, we hypothesized that VA protective effect of statin could be inhibition of YAP/TAZ pathway via MA reduction.
Methods
Patients on maintenance hemodialysis and people with stage 4 or 5 chronic kidney disease were enrolled in this study. The serum MA levels were measured using an enzyme cycling method. Gene expressions of connective tissue growth factor (CTGF) and cysteine-rich angiogenic inducer 61 (CYR61) in the peripheral blood mononuclear cells were evaluated using real-time PCR.
Results
Serum MA levels in patients with CKD and maintenance hemodialysis increased compared to healthy subjects (6.6±0.7, 8.8±0.6, and 4.6±0.8 µg/dL, respectively). Among hemodialysis patients, serum MA levels were higher in patients with VA dysfunction than without dysfunction (9.2±0.6 vs 6.6±0.7 µg/dL, p=0.07). Moreover, serum MA levels in patients who required VA angioplasty more than a year showed a higher value than those without repeated angioplasty (9.4±0.9 vs 8.7±0.7 µg/dL, p=0.60). These data suggest that serum MA levels associate with an increased risk of VA dysfunction. Serum MA levels were lower in statin users compared to non-users (7.4±1.1 vs 9.4±0.6 µg/dL, p=0.10), indicating that statin could decrease serum MA levels. Lastly, CTGF and CYR61 gene expressions were decreased in statin users compared to non-users (0.13±0.02 vs 0.17±0.01, 0.48±0.05 vs 0.67±0.11, respectively), implying that statin inhibits the YAP/TAZ pathway.
Conclusion
Statin treatment could be effective on VA dysfunction through lowering MA and YAP/TAZ suppression.
Funding
- Private Foundation Support