Li Shiwei, Wang Xuemei, Liu Ming
Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
Department of Endocrinology and Nephrology, Tianjin Ninghe Hospital, Tianjin, China.
J Clin Invest. 2025 Aug 1;135(15). doi: 10.1172/JCI195624.
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.
肾结石病（KSD）源于遗传易感性、饮食、代谢紊乱及其他环境因素之间的复杂相互作用。在本期《临床研究杂志》（JCI）中，洛夫格罗夫等人报告了一项大规模全基因组关联研究（GWAS），该研究确定了71个与肾结石病风险增加相关的基因座。通过结合孟德尔随机化和功能验证的综合方法，他们强调了二酰甘油激酶δ（DGKD）、溶质载体家族34成员1（SLC34A1）和细胞色素P450 24A1（CYP24A1）在维持钙和磷稳态中的作用。这些发现为肾结石病的发病机制提供了见解，并提示了潜在的干预靶点。需要进一步的研究来在不同人群和临床环境中验证这些发现。
