Clinical trial NCT03901521: Autosomal Dominant Polycystic Kidney Disease Somatic Mutation Biorepository
Official title: Autosomal Dominant Polycystic Kidney Disease Somatic Mutation Biorepository
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Autosomal Dominant Polycystic Kidney Disease
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: The Rogosin Institute
First posted: 2019-04-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Inclusion criteria include patients with a diagnosis of end-stage renal disease caused by ADPKD who are scheduled for native nephrectomy. The clinical indications for native nephrectomy will be determined by the surgeon prior to enrollment of the subject. These patients will be identified during the pre-operative evaluation that occurs prior to the surgery. At the time of this evaluation, subject eligibility will be assessed by a co-investigator and their willingness to participate will be evaluated. Subjects who agree to participate will provide informed consent, and blood samples (30 mL) will be obtained for extraction of nucleic acids, in addition to the routine preoperative blood tests.

Brief summary: This study will analyze the germline and somatic mutations underlying the development of ADPKD in order to better understand the genetic mechanism responsible for the cystic transformation. Once identified, these mutations could help us understand better the mechanism leading to the development of this disease and may explain at least in part the phenotypic variability.

Detailed description: The presentation of ADPKD renal and extrarenal manifestations varies widely, even within families, and has been attributed to numerous genetic factors. One principal explanation came with the discovery that renal cyst lining cells from ADPKD patients undergo secondary somatic mutations, selective loss of the second copy of a respective normal polycystic kidney disease (PKD) gene. These somatic mutations can occur in either polycystic kidney disease 1 (PKD1) or polycystic kidney disease 2 (PKD2). Furthermore, various cysts in the same patient have been reported to harbor different somatic mutations. These findings implicated a cellular recessive mechanism for cyst formation in ADPKD, suggesting the possibility that the observed intra-familial variation in disease phenotype may, at least in part, be explained by variation in mutation type, the timing and number of somatic "second-hit" mutations in individual family members affected with the disease. However, there is currently very little known about the cellular genetic mechanism leading to cysts development and very few studies, addressing this issue.

Eligibility criteria: Inclusion Criteria:

* Males or females
* 18 years of age or older
* Confirmed diagnosis of ADPKD
* Undergoing a native nephrectomy
* Willing and able to provide informed consent

Exclusion Criteria:

* Unable or unwilling to provide informed consent

Primary outcomes:
measure: The presence of somatic PKD 1/2 gene mutations in cyst epithelial cells
timeFrame: 10 YEARS
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Priya Velu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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