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The following is a summary of “Yield of genetic testing in management of Nephrolithiasis,” published in the July 2024 issue of Urology by Pearce et al.

This study aims to comprehensively analyze the yield and clinical indications for genetic testing in patients diagnosed with nephrolithiasis. With technological advancements facilitating rapid accessibility, the investigation focuses on delineating the diagnostic efficacy of genetic testing among high-risk stone formers and identifying specific 24-hour urine parameters that could prompt genetic screening.

Retrospective data from 2020 to 2022 were reviewed, identifying patients who underwent genetic testing for nephrolithiasis at a single institution using a specialized PerkinElmer™ genomics panel. Comparative analysis was conducted between patients with detected genetic abnormalities and those without. Receiver operating characteristic (ROC) analysis was employed to determine potential thresholds for initiating genetic testing based on urinary biochemical profiles.

Among 36 patients tested, genetic mutations were identified in 39% (14/36). Notably, 14% (5/36) harbored known pathogenic mutations associated with primary hyperoxaluria (PH2 and PH3), cystinuria, and enamel renal syndrome. The majority of identified mutations were variants of uncertain significance. Importantly, only 6 of the 14 patients with mutation-positive exhibited concurrent abnormalities in 24-hour urine profiles, including 3 out of 5 with known pathogenic mutations. Within the subgroup exhibiting urine oxalate levels ≥40mg/day, 10.3% (3/29) were diagnosed with PH2 or PH3. ROC analysis suggested that a threshold of ≥80mg/day for urine oxalate could be a reliable indicator for genetic screening.

Genetic testing in nephrolithiasis management remains a topic of debate due to uncertainties surrounding its diagnostic yield and the substantial effort required to discuss results with patients. This study provides preliminary insights into the diagnostic yield of genetic testing, highlighting specific clinical indicators and a potential threshold for urine oxalate that may guide clinicians in determining appropriate candidates for genetic profiling. Further research is warranted to validate these findings and optimize the clinical utility of genetic testing in nephrolithiasis.

Source: sciencedirect.com/science/article/abs/pii/S0090429524005557