Genetic Variations That Increase the Risk for Calcium Kidney Stones: a Family-based Study

NCT06211842 | Completed

• 1 other identifier: RHM PAT0295
• Study Type: observational
• Target: 47
• Locations: 0 countries
• Sites: N/A

Brief Summary

Many things, like not drinking enough fluids, contribute to making kidney stones and there is also a genetic tendency. We looked into this in 1998-2000 in 14 families with several stone-formers. In four of these the risk for stones was passed down through one line of the family. We have now had a close look at the DNA of 47 members of these four families using a very sensitive technique called exome sequencing. We wanted to see if these individuals had inherited any rare changes (variations) in their DNA which would add to their risk of making stones. We found 11 variations which might be important. Surprisingly, these were not in genes which have been regarded as the main causes of stones. Most of them are unfamiliar to clinicians and scientists world-wide. Experts on the genes gave us helpful advice about the likely significance of the variations. Researchers in Paris, Lille and the UK (Oxford, Cambridge and Sheffield) did analyses to help to decide this. An exciting finding was that one of the variants, not previously identified in stone formers, had just been found in a large Italian family with stones. This small study has shown that: variations in a wide range of genes may contribute to stone formation; these occur in genes that we have not come across before; further laboratory studies are essential to investigate potentially important variants; sharing findings between laboratories doing similar studies world-wide is crucial.

Conditions

Urolithiasis

Keywords

gene polymorphisms

Outcome Measures

Primary Outcomes (1)

• Gene variants linked to kidney stone formation

  The number of stone-formers within a kindred with a gene variant relevant to stones compared with the number of non-stone formers with the variant in the kindred. Stone formation ascertained from interviews with family members in 1998-2000, follow-up questionnaires in 2016 and hospital records.

  up to 12 months from end of the study to complete functional studies of identified variants

Secondary Outcomes (1)

• Gene variants linked to biochemical traits which increase the risk for kidney stones.

  up to 12 months from end of the study to complete functional studies of identified variants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Four families met the above criteria. A total of 77 family members in primary care were eligible. Of these: 71 were contacted: 47 were recruited; 3 declined; and 21 did not respond to two letters of invitation

You may qualify if:

• Stone-forming families who participated in our 1998-2000 study
• Apparent autosomal dominant inheritance of stones transmitted through one line of the family.
• Calcium kidney stone formers.
• Men and women aged 18 year or over.

You may not qualify if:

• A known hereditary cause of stones
• Children under 18 years of age.
• Uric acid stone formers.

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• University of Southampton: collaborator

Related Publications (1)

• Jabalameli MR, Fitzpatrick FM, Colombo R, Howles SA, Leggatt G, Walker V, Wiberg A, Kunji ERS, Ennis S. Exome sequencing identifies a disease variant of the mitochondrial ATP-Mg/Pi carrier SLC25A25 in two families with kidney stones. Mol Genet Genomic Med. 2021 Dec;9(12):e1749. doi: 10.1002/mgg3.1749. Epub 2021 Aug 4.

  PMID: 34346195 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

DNA extracted from stored whole blood will be retained for use in other studies subject to the consent of the participants (46 consented). DNA from 1 participant who did not consent to this will be discarded

MeSH Terms

Conditions

Urolithiasis

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Paul Cook, MRCPPhDFRCPa

  University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 18, 2024
• Study Start: October 12, 2016
• Primary Completion: May 25, 2022
• Study Completion: November 8, 2023
• Last Updated: January 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: When the request for information is made \& has been approved by Dr Walker or the PI. No time limit since this is anonymised data
• Access Criteria: Email approach to Dr Walker or the PI who will review the request. Details of the gene variants found and biochemical data from the original study will be shared.