Clinical trial NCT03726463: Evaluation of Iliac and Renal Artery for Mechanism of Intracranial Aneurysm in ADPKD
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Kidney Transplant; Complications
Polycystic Kidney Diseases
Aneurysm, Brain
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2018-10-31
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: ADPKD patients from ages 18 to 80 receiving kidney transplantation at Asan Medical Center, which consists of approximately 2.8% of kidney transplantation patients

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Intracranial aneurysm
timeFrame: through study completion, average of 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
References:
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