Evaluation of Nephrectomy Specimen for Intracranial Aneurysm Development in ADPKD

March 25, 2019 updated by: Sung Shin, Asan Medical Center

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

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.

Study Overview

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, 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.

Study Type

Observational

Enrollment (Actual)

154

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
polycystic kidney disease
Adult autosomal dominant polycystic kidney disease patients who received kidney transplantation at Asan Medical Center between 1994 and 2018
Bilateral nephrectomy of polycystic kidneys are routinely performed during kidney transplantation in ADPKD patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial aneurysm
Time Frame: average of 5 years
Occurrence of intracranial aneurysm
average of 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 1994

Primary Completion (Actual)

December 31, 2018

Study Completion (Actual)

December 31, 2018

Study Registration Dates

First Submitted

March 18, 2019

First Submitted That Met QC Criteria

March 25, 2019

First Posted (Actual)

March 26, 2019

Study Record Updates

Last Update Posted (Actual)

March 26, 2019

Last Update Submitted That Met QC Criteria

March 25, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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