Presented by: Robert Pearce BA
University of California, San Francisco, Department of Urology

Introduction

There are no established guidelines regarding indications for genetic testing in stone formers. 24-hour urine testing has long been utilized to identify downstream urinary abnormalities to target for treatment in hopes of preventing recurrent kidney stones. However, few studies have explored the relationship between genetic mutations and 24-hour urine results. In this study, we hypothesized that patients with abnormal 24-hour urine analytes would be more likely to test positive for genetic abnormalities.

Materials

We retrospectively identified patients who underwent genetic testing to assess etiology of nephrolithiasis between 2020 and 2022 at a single institution using the PerkinElmers specialized genomics panel for nephrolithiasis. The most common reason for genetic testing was hyperoxaluria (>40mg/day) without enteric etiology. Analyses were performed to compare patient characteristics with and without genetic abnormalities. We also performed cutpoint analysis to identify candidate thresholds for genetic testing.

Results

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14 of 36 patients who underwent genetic testing had identifiable mutations. The most commonly found mutations were associated with cystinuria, xanthinuria and primary hyperoxaluria.  Of the 29 patients tested with hyperoxaluria, the mean oxalate level was 71mg/day (± 32) and three were found to have primary hyperoxaluria types 2 and 3. Cutpoint analysis showed that using a urinary oxalate value greater than 80mg/day, 60% of patients were found to have a genetic abnormality (Figure 1). A trend was noted toward a higher proportion of genetic mutations with increasing oxalate cutoffs. A similar cutpoint analysis for calcium revealed that 60% of patients with urinary calcium >120mg/day had a genetic abnormality; most of these patients were found to have cystinuria, xanthinuria, or primary hyperoxaluria.

Conclusion

Genetic testing in patients with nephrolithiasis remains controversial due to the unknown yield of positive results and the time and energy required to discuss these with our patients. This preliminary report identifies potential cut-offs that may help guide the clinician to decide when a genetic profile should be undertaken to help determine optimal therapy. In our practice, this was used to identify and confirm candidates for clinical trial enrollment for cystinuria and primary hyperoxaluria.

Funding

None

Lead Authors

Wilson Sui, MD
University of California, San Francisco, Department of Urology

Co-Authors

Heiko Yang, MD, PHD
University of California, San Francisco, Department of Urology

Thomas Chi, MD
University of California, San Francisco, Department of Urology

Marshall Stoller, MD
University of California, San Francisco, Department of Urology