Evaluation of Nephrectomy Specimen for Intracranial Aneurysm Development in ADPKD

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 the investigator's 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. Total 154 patients received kidney transplantation for ADPKD from 1994 to December 2018 at Asan Medical Center, Seoul, Korea. While performing kidney transplantation to ESRD ADPKD patients, nephrectomy has been routinely performed for polycystic kidney and the nephrectomy specimens can be obtained. The objective of this study is to investigate the mechanism of intracranial aneurysm in ADPKD patients by analyzing gene characteristics from nephrectomy specimens.

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Key information

Conditions

Kidney Transplant; Complications Abnormalities, Multiple Aneurysm Aneurysm, Brain Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Intracranial Aneurysm Intracranial Arterial Diseases Kidney Diseases Kidney Diseases, Cystic Male Urogenital Diseases Nervous System Diseases Polycystic Kidney Diseases Urogenital Diseases Urologic Diseases Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Observational

About this study

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, the investigators plan to perform PKD gene tests and gene sequencing from polycystic kidney nephrectomy specimens of154 ADPKD patients who received kidney transplantation at Asan Medical Center between 1994 and 2018. The aim of this study to analyze the gene mutation of ADPKD patients and investigate mechanisms associated with intracranial aneurysm occurence in ADPKD patients.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Adult patients between age 18 and 80,
Patients who received kidney transplantation for ADPKD at Asan Medical Center between 1994 and 2018,
Patients who received nephrectomy for polycystic kidney

Exclusion criteria

those who refuse or are unable to provide consent form,
pregnancy

Treatment and study plan

Kidney transplantation and nephrectomy

Procedure

Bilateral nephrectomy of polycystic kidneys are routinely performed during kidney transplantation in ADPKD patients

Primary outcomes

Intracranial aneurysm

Time frame: average of 5 years

Occurrence of intracranial aneurysm

Sponsors and collaborators

Lead sponsor

Asan Medical Center

Other

Registry information

Official study title

Evaluation of Nephrectomy Specimen to Verify a Mechanism of Intracranial Aneurysm Development in Autosomal Dominant Polycystic Kidney Disease Patients

Important dates

Study start: 1994
Primary completion: 2018
Study completion: 2018
First posted: Mar 26, 2019
Registry last updated: Mar 26, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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