Work

Understanding the clinical genetics of kidney stone disease using the Natera Renasight panel

Year: 2025

Type: article

Abstract: We aimed to characterize the underlying genetics of kidney stone disease (KSD) in an urban and diverse population using the Natera Renasight genetic panel. This was a single-center prospective study of high-risk KSD patients, defined as recurrent stone formers or those with a family history with KSD. Buccal saliva DNA samples were collected with the commercially available Natera Renasight genetic panel and were analyzed using next-generation sequencing. The panel assesses 385 kidney disease related genes, including 45 linked to KSD. One hundred eleven high-risk KSD patients were enrolled. The majority were female (56%) with a median age of 50 (IQR 39.5-59.5), compromising a diverse ethnic background with 62% Hispanic, 23% White and 11% Black. Patients had median 3 (IQR 2-5) lifetime stone episodes, and 41% had family history of KSD. Genetic analysis was possible for 105 patients (95%). Eight (8%) had positive tests with only one patient found to have a pathogenic mutation associated with KSD (SLC7A9, cystinuria). The other 7 positive tests 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 tests 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). Our study sheds light on genetic factors of KSD in a diverse patient population. The results suggest that KSD is unlikely monogenetic in nature, but 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.

Source: Urolithiasis

DOI: 10.1007/s00240-025-01723-2