Department of Urology, University of California San Francisco, San Francisco, CA.
Department of Urology, University of California San Francisco, San Francisco, CA.
Urology. 2024 Nov;193:27-34. doi: 10.1016/j.urology.2024.07.002. Epub 2024 Jul 9.
To describe the yield and indications for performing genetic testing in patients with nephrolithiasis. Genetic testing for nephrolithiasis is becoming more accessible and rapid due to technologic advances. This study aimed to determine the diagnostic yield of genetic testing in a cohort of high-risk stone formers and to identify 24-hour urine characteristics to prompt genetic screening.
We retrospectively identified patients who underwent genetic testing for nephrolithiasis from 2020 to 22 at a single institution using a custom PerkinElmer genomics panel for nephrolithiasis. We compared characteristics of patients with and without genetic abnormalities. We used receiver operator characteristic (ROC) analysis to identify candidate thresholds for genetic testing.
Fourteen of 36 patients (39%) who underwent genetic testing had identifiable mutations. Five patients (14%) had known pathogenic mutations, including genes for primary hyperoxaluria (PH2 and PH3), cystinuria, and enamel-renal syndrome. The remaining mutations were variants of uncertain significance. Of the 14 patients with identified mutations, only 6 had concordant 24-hour urine abnormalities, including 3/5 with known pathogenic mutations. In patients with urine oxalate ≥ 40 mg/day, 3/29 (10.3%) had PH2 or PH3. ROC analysis showed that an oxalate threshold of ≥ 80 mg/day may have promising screening characteristics.
Genetic testing for nephrolithiasis remains controversial due to unknown yield and the time and energy required to discuss results with patients. This preliminary report describes the yield and identifies clinical factors and a potential cut-off that may assist clinicians in deciding when genetic profiling should be pursued.
描述肾结石患者进行基因检测的产量和适应证。由于技术进步，肾结石的基因检测变得更加便捷和快速。本研究旨在确定遗传检测在高风险结石形成者中的诊断产量，并确定 24 小时尿液特征以提示遗传筛查。
我们使用定制的 PerkinElmer 肾结石基因组学检测 panel，回顾性地确定了 2020 年至 2022 年期间在一家机构接受肾结石基因检测的患者。我们比较了有和无遗传异常患者的特征。我们使用接受者操作特征 (ROC) 分析来确定基因检测的候选阈值。
在接受基因检测的 36 名患者中，有 14 名（39%）患者可识别出突变。有 5 名患者（14%）有已知的致病性突变，包括原发性高草酸尿症（PH2 和 PH3）、胱氨酸尿症和牙釉质-肾综合征的基因。其余突变是意义不明的变异。在 14 名有明确突变的患者中，只有 6 名患者的 24 小时尿液异常具有一致性，包括 3/5 名有已知致病性突变的患者。在尿草酸盐≥40mg/天的患者中，有 3/29（10.3%）患者存在 PH2 或 PH3。ROC 分析显示，草酸阈值≥80mg/天可能具有有前途的筛查特征。
由于遗传检测的产量未知，以及与患者讨论结果所需的时间和精力，肾结石的基因检测仍然存在争议。本初步报告描述了产量，并确定了临床因素和潜在的截止值，可能有助于临床医生决定何时应进行基因分析。
