Evaluation of Nephrectomy Specimen for Intracranial Aneurysm Development in ADPKD
Condition: Kidney Transplant; Complications; Aneurysm, Brain; Polycystic Kidney Diseases
MeSH terms: Intracranial Aneurysm; Kidney Diseases; Polycystic Kidney Diseases; Aneurysm
Study type: Observational

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 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.
    

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.
    

Intervention name(s): Kidney transplantation and nephrectomy
Intervention type(s): Procedure
Intervention description(s): Bilateral nephrectomy of polycystic kidneys are routinely performed during kidney transplantation in ADPKD patients
Observational model: Cohort
Time perspective: Retrospective
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
      
Biospecimen description: 
      polycystic kidney specimen from nephrectomy operation during kidney transplantation