MP63-04 CLINICAL GENETICS OF KIDNEY STONE DISEASE USING THE NATERA® RENASIGHT™ KIDNEY GENE PANEL

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP63)1 May 2024MP63-04 CLINICAL GENETICS OF KIDNEY STONE DISEASE USING THE NATERA® RENASIGHT™ KIDNEY GENE PANEL Andrewe Baca, Rutul Patel, Kevin Labagnara, Benjamin Green, Michael Zhu, Kavita Gupta, Andrea Asencio, Deep Sharma, Wei Chen, Dima Raskolnikov, Jillian Donnelly, Kara Watts, and Alexander C. Small Andrewe BacaAndrewe Baca , Rutul PatelRutul Patel , Kevin LabagnaraKevin Labagnara , Benjamin GreenBenjamin Green , Michael ZhuMichael Zhu , Kavita GuptaKavita Gupta , Andrea AsencioAndrea Asencio , Deep SharmaDeep Sharma , Wei ChenWei Chen , Dima RaskolnikovDima Raskolnikov , Jillian DonnellyJillian Donnelly , Kara WattsKara Watts , and Alexander C. SmallAlexander C. Small View All Author Informationhttps://doi.org/10.1097/01.JU.0001009436.52988.91.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The etiology of kidney stone disease (KSD) is multifactorial, but genetic links are more common than previously believed. Monogenetic mutations may cause up to 11% of KSD; other heritable factors may contribute to ≥56% cases. We investigated genetics of KSD using the Natera® Renasight™ genetic panel within a diverse patient population. METHODS: This was a single-center prospective study of high-risk KSD patients (i.e., recurrent KSD or KSD plus family history) without known genetic disorders. Buccal saliva DNA samples collected with a Natera® Renasight™ kit were analyzed using next-generation sequencing. The test assesses 385 kidney disease genes, of which 44 are linked to KSD. Tests were categorized as "positive" (pathogenic mutation), "carrier" (autosomal recessive carrier), or "VUS" (only variants of unknown significance). RESULTS: 111 high-risk KSD patients were enrolled. 56% were female; 62% were Hispanic and 11% were Black. The median age was 50 years (IQR 40-60). 105 (95%) provided samples sufficient for genetic analysis. 8 (8%) had positive tests -- only 1 had a KSD-associated pathogenic mutation (SLC7A9, cystinuria), and 7 others included amyloidosis (TTR, N=3), Alport syndrome (COL4A3, N=2), polycystic kidney disease (PKD1, N=1), and susceptibility to ESRD (APOL1, N=1). Patients with positive test were more likely to have chronic kidney disease (38% vs 5%, p<0.01), gout (13% vs 1%, p=0.02) and carbonate apatite stones (38% vs 7%, p<0.01). 49 (47%) were carriers for 66 unique genes, of which 8 (16%) were carriers of KSD genes. All patients had multiple VUS spanning 279 unique genes, of which 57 (54%) had VUS linked to KSD genes. There were no significant differences between KSD-linked VUS and other VUS in demographics or comorbidities. CONCLUSIONS: Our study sheds light on genetic factors of KSD in a diverse patient population. The results suggest that KSD is unlikely to have a monogenetic cause, and is more likely due to a complex interplay of polygenetic and environmental influences. Genetic testing may be most useful in KSD patients with chronic kidney disease. Download PPT Source of Funding: This study was funded by a grant from Natera® Inc © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1032 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Andrewe Baca More articles by this author Rutul Patel More articles by this author Kevin Labagnara More articles by this author Benjamin Green More articles by this author Michael Zhu More articles by this author Kavita Gupta More articles by this author Andrea Asencio More articles by this author Deep Sharma More articles by this author Wei Chen More articles by this author Dima Raskolnikov More articles by this author Jillian Donnelly More articles by this author Kara Watts More articles by this author Alexander C. Small More articles by this author Expand All Advertisement PDF downloadLoading ...