尿酸性肾结石中代谢发病机制的现状 与展望

Metabolic Pathogenesis of Uric Acid Nephrolithiasis: Current Status and Perspectives

摘要: 尿酸性肾结石是泌尿系统常见疾病，全球患病率呈逐步上升趋势，复发率高，且与代谢综合征、肥胖及2型糖尿病密切相关，疾病负担重。近年来研究将其重新认识为一种与全身代谢异常紧密关联的系统性疾病，其中内脏脂肪堆积驱动的胰岛素抵抗通过损害肾小管泌氨功能导致持续性低尿pH，构成核心致病环节。本文从流行病学趋势与结石谱系变迁、体成分异常与代谢紊乱、尿液理化异常机制、肠–肾代谢轴、遗传与分子机制及饮食与环境因素六个维度，系统综述了尿酸性肾结石代谢发病机制的研究进展，重点阐述了内脏脂肪、胰岛素抵抗与低尿pH在结石形成中的关键作用，明确代谢综合征各组分通过胰岛素抵抗–低尿pH通路及高尿酸尿通路协同促进结石形成。体成分多维评估具有超越传统体质量指数的风险分层潜力，可为精准预防提供新工具。未来将以整合多组学技术、构建精准预测模型、开发靶向代谢与肠道菌群的新型干预策略为主要方向，推动尿酸性肾结石从经验性预防向个体化精准管理的临床转化。

Abstract: Uric acid nephrolithiasis is a common urological disease with progressively increasing global prevalence and a high recurrence rate. It is closely associated with metabolic syndrome, obesity, and type 2 diabetes mellitus, imposing a substantial disease burden. Recent studies have redefined this condition as a systemic disorder intimately linked to generalized metabolic dysfunction, in which visceral adiposity-driven insulin resistance impairs renal tubular ammoniagenesis, leading to persistently low urinary pH—the core pathogenic mechanism. This review systematically examines the metabolic pathogenesis of uric acid nephrolithiasis across six dimensions: epidemiological trends and stone composition shifts, body composition abnormalities and metabolic disturbances, urinary physicochemical derangements, the gut-kidney metabolic axis, genetic and molecular mechanisms, and dietary and environmental factors. Emphasis is placed on the pivotal role of visceral adiposity, insulin resistance, and low urinary pH in stone formation, highlighting how individual components of metabolic syndrome synergistically promote stone formation through the insulin resistance-low urinary pH axis and the hyperuricosuria pathway. Multidimensional body composition assessment offers risk stratification potential that surpasses that of traditional body mass index, providing a novel tool for precision prevention. Future research should prioritize integrating multi-omics technologies, constructing precision prediction models, and developing novel intervention strategies targeting metabolism and the gut microbiota, thereby accelerating the clinical translation of uric acid nephrolithiasis management from empirical prevention to individualized precision care.