Presented by: Nicolette Payne MD
Mayo Clinic Arizona, Department of Urology

Introduction

Recent studies have shown that up to 10% of adult stone formers have an underlying monogenic cause. Over 30 genes contributing to stone formation have been identified, but additional clinically significant genetic variants remain unidentified. We sought to describe genetic and clinical characteristics for patients undergoing genetic testing at a large urology practice with a multi-disciplinary stone clinic

Materials

A retrospective review was performed on patients evaluated in our multi-disciplinary stone clinic and referred to our nephrolithiasis genetics clinic between 2018 and 2022. Patient demographic, clinical, stone, and genetic data were included. Specifically, we included stone history, composition, as well as the presence or absence of a genetic variant and its associated pathogenic significance if known.

Results

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Of 825 patients seen in the multi-disciplinary stone clinic from 2018-2022, 50 patients were referred to the nephrolithiasis genetics clinic. Among these patients, 33 (66%) underwent genetic testing and were included in analysis. Genetic testing identified a variant in 19 (58%) patients of which 6 (32%) had a variant with a known pathogenic association. For patients with a variant identified, the majority had a family history of stones (68%), a prior stone event (95%), calcium-based stones (68%), and had undergone medical (79%) or surgical (79%) management prior to testing. A large proportion (37%) had their first stone episode prior to age 18. There were no significant differences in demographic or clinical parameters between patients with pathogenic variants vs. variants of unknown significance (VUS). Solute-carrier (SLC) gene abnormalities were the most common variants identified among both groups.

Conclusion

Among a high volume, multidisciplinary stone practice, more than half of the patients referred for a genetics consultation were found to have a genetic variant. However, the majority of these variants were of unknown significance. Further evaluation into associations of these VUS with clinical indicators/outcomes is warranted.

Funding

None

Co-Authors

Sayi Boddu, BA
Mayo Clinic Alix School of Medicine

Kevin Wymer, MD
Mayo Clinic Arizona, Department of Urology

Daniel Heidenberg, MD
Mayo Clinic Arizona, Department of Urology

Charles Van De Walt, BS
Mayo Clinic, Department of Qualitative Health Sciences

Lanyu Mi, MS
Mayo Clinic, Department of Qualitative Health Sciences

Mira Keddis, MD
Mayo Clinic Arizona, Department of Nephrology

Karen Stern, MD
Mayo Clinic Arizona, Department of Urology