Autosomal Dominant Polycystic Kidney Disease Somatic Mutation Biorepository

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

— ADPKD  

Official title:

Autosomal Dominant Polycystic Kidney Disease Somatic Mutation Biorepository

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03901521
• Other study ID #: 1710018665
• Status: Enrolling by invitation
• Start date: June 1, 2018
• Est. completion date: December 31, 2028

Study information

• Verified date: August 2023
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2028
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthrogryposis
• Autosomal Dominant Polycystic Kidney Disease
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Locations

Country	Name	City	State
United States	Weill Cornell Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	The Rogosin Institute

Country where clinical trial is conducted

United States, 

References & Publications (7)

Ben-Dov IZ, Tan YC, Morozov P, Wilson PD, Rennert H, Blumenfeld JD, Tuschl T. Urine microRNA as potential biomarkers of autosomal dominant polycystic kidney disease progression: description of miRNA profiles at baseline. PLoS One. 2014 Jan 29;9(1):e86856. — View Citation

Tan AY, Blumenfeld J, Michaeel A, Donahue S, Bobb W, Parker T, Levine D, Rennert H. Autosomal dominant polycystic kidney disease caused by somatic and germline mosaicism. Clin Genet. 2015 Apr;87(4):373-7. doi: 10.1111/cge.12383. Epub 2014 Apr 26. — View Citation

Tan AY, Michaeel A, Liu G, Elemento O, Blumenfeld J, Donahue S, Parker T, Levine D, Rennert H. Molecular diagnosis of autosomal dominant polycystic kidney disease using next-generation sequencing. J Mol Diagn. 2014 Mar;16(2):216-28. doi: 10.1016/j.jmoldx. — View Citation

Tan AY, Zhang T, Michaeel A, Blumenfeld J, Liu G, Zhang W, Zhang Z, Zhu Y, Rennert L, Martin C, Xiang J, Salvatore SP, Robinson BD, Kapur S, Donahue S, Bobb WO, Rennert H. Somatic Mutations in Renal Cyst Epithelium in Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2018 Aug;29(8):2139-2156. doi: 10.1681/ASN.2017080878. Epub 2018 Jul 24. — View Citation

Zhang W, Stephens CJ, Blumenfeld JD, Behzadi AH, Donahue S, Bobb WO, Newhouse JH, Rennert H, Zhao Y, Prince MR. Relationship of Seminal Megavesicles, Prostate Median Cysts, and Genotype in Autosomal Dominant Polycystic Kidney Disease. J Magn Reson Imaging — View Citation

Zhang W, Tan AY, Blumenfeld J, Liu G, Michaeel A, Zhang T, Robinson BD, Salvatore SP, Kapur S, Donahue S, Bobb WO, Rennert H. Papillary renal cell carcinoma with a somatic mutation in MET in a patient with autosomal dominant polycystic kidney disease. Can — View Citation

Zhang Z, Bai H, Blumenfeld J, Ramnauth AB, Barash I, Prince M, Tan AY, Michaeel A, Liu G, Chicos I, Rennert L, Giannakopoulos S, Larbi K, Hughes S, Salvatore SP, Robinson BD, Kapur S, Rennert H. Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome Sequencing. J Am Soc Nephrol. 2021 Dec 1;32(12):3114-3129. doi: 10.1681/ASN.2021050690. Epub 2021 Dec 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The presence of somatic PKD 1/2 gene mutations in cyst epithelial cells	The presence of mutations will be measured by next generation sequencing (NGS) and other tools for mutation analysis.	10 YEARS