Evaluation of Iliac and Renal Artery for Mechanism of Intracranial Aneurysm in ADPKD

Kidney Transplant; Complications Clinical Trial

Official title:

Evaluation of Intima and Media Layer of Iliac and Renal Artery to Verify a Mechanism of Intracranial Aneurysm Development in Autosomal Dominant Polycystic Kidney Disease Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03726463
• Other study ID #: 2018-1210
• Status: Recruiting
• Start date: December 20, 2018
• Est. completion date: November 2023

Study information

• Verified date: March 2019
• Source: Asan Medical Center
• Contact: Sung Shin, MD, PhD
• Phone: 82-2-3010-3964
• Email: sshin[@]amc.seoul.kr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

ADPKD is the most common form of hereditary kidney disease and is known to occur in 1 of 400 to 1000 population in the U.S. ADPKD consists of 2.8% of patients receiving kidney transplantation in our center. It is known that ADPKD is associated with vascular anomalies, including abdominal aneurysms, valvular anomalies and especially intracranial aneurysms. Intracranial aneurysms occur in 9~12% of the ADPKD population which is higher than 2~3% in the general population and is known to be associated with PKD1 or PKD2 heritage.

Until now, most of the studies regarding intracranial aneurysms in ADPKD are conducted in animal models, and there are only few cellular studies conducted from human samples. While performing kidney transplantation to ESRD ADPKD patients, arterial tissues from nephrectomy specimens can be obtained. The objective of this study is to investigate the mechanism of intracranial aneurysm in ADPKD patients by analyzing iliac and renal artery characteristics.

Description:

ADPKD is associated with PKD1 gene on chromosome 16 and PKD2 gene on chromosome 4 and these gene respectively code polycystin 1 and polycystin 2. Currently the hypotheses for increased intracranial aneurysm rate in ADPKD patients is that mutation of polycystin is not only confined to nephron tissues but also in endothelial cells and vascular smooth muscle cells and results in mutation of vascular phenotype. Also recent studies show polycystin complex causes cystic changes through mutation in primary cilia in renal epithelium. Wild type endothelial cells respond to fluid shear stress by regulating levels of intracellular calcium and nitric oxide, however, PKD1 or PKD2 mutation in fetal aortic endothelial cells revealed loss of these responses.

During kidney transplantation, bilateral nephrectomies are routinely performed to ADPKD patients. In this study, blood, urine, iliac artery and renal artery tissues will be collected from ADPKD patients receiving kidney transplantation to analyze the arterial characteristic and gene mutation of ADPKD patients. The aim of this study is to evaluate mechanisms associated with intracranial aneurysm occurence in ADPKD patients by analyzing the genetic mutation and vascular deformities of these patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 2023
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• ADPKD patients from ages 18 to 80 receiving kidney transplantation at Asan Medical Center

Exclusion Criteria:

• those who refuse or are unable to provide consent form

• pregnancy

Related Conditions & MeSH terms

• Aneurysm
• Aneurysm, Brain
• Intracranial Aneurysm
• Kidney Diseases
• Kidney Transplant; Complications
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Procedure:
• Kidney transplantation
Bilateral nephrectomy of polycystic kidneys are routinely performed during kidney transplantation in ADPKD patients

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (4)

Collins AJ, Foley RN, Chavers B, Gilbertson D, Herzog C, Johansen K, Kasiske B, Kutner N, Liu J, St Peter W, Guo H, Gustafson S, Heubner B, Lamb K, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Thompson B, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Daniels F, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers P, Agodoa L. 'United States Renal Data System 2011 Annual Data Report: Atlas of chronic kidney disease & end-stage renal disease in the United States. Am J Kidney Dis. 2012 Jan;59(1 Suppl 1):A7, e1-420. doi: 10.1053/j.ajkd.2011.11.015. — View Citation

Ecder T, Schrier RW. Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease. Nat Rev Nephrol. 2009 Apr;5(4):221-8. doi: 10.1038/nrneph.2009.13. Review. — View Citation

Iglesias CG, Torres VE, Offord KP, Holley KE, Beard CM, Kurland LT. Epidemiology of adult polycystic kidney disease, Olmsted County, Minnesota: 1935-1980. Am J Kidney Dis. 1983 May;2(6):630-9. — View Citation

Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007 Apr 14;369(9569):1287-1301. doi: 10.1016/S0140-6736(07)60601-1. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intracranial aneurysm	Occurrence of intracranial aneurysm	through study completion, average of 2 years