Autosomal Dominant Polycystic Kidney Disease Somatic Mutation Biorepository

• Conditions: Autosomal Dominant Polycystic Kidney Disease

• Registration Number: NCT03901521
• Lead Sponsor: Weill Medical College of Cornell University

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.

Study Timeline

• Study Start: 2018-06-01
• Study First Submitted: 2019-03-13
• Study First Submitted QC: 2019-04-02
• Study First Posted: 2019-04-03
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-21
• Last Update Posted: 2025-02-24
• Primary Completion: 2028-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The presence of somatic PKD 1/2 gene mutations in cyst epithelial cells	10 YEARS	The presence of mutations will be measured by next generation sequencing (NGS) and other tools for mutation analysis.

Trial Locations

Locations (1)

Weill Cornell Medicine; 🇺🇸 New York, New York, United States