Genetic susceptibility to kidney stone disease: unveiling pathogenesis and potential therapeutic targets

Kidney stone disease (KSD) arises from a complex interplay of genetic predisposition, diet, metabolic disorders, and other environmental factors. In this issue of the JCI, Lovegrove et al. report a large GWAS that identifies 71 loci associated with an increased risk of KSD. Through an integrative approach combining Mendelian randomization and functional validation, they emphasize the roles of DGKD, SLC34A1, and CYP24A1 in maintaining homeostasis of calcium and phosphate. These findings offer insights into the pathogenesis of KSD and suggest potential targets for intervention. Further studies are needed to validate these findings across diverse populations and clinical settings.