Multifaceted Perspectives on Kidney Stone Disease: Pathogenesis, Integrating Diet, Genetics, Management, and Emerging Global Challenges Across the Lifespan

Kidney stone disease (KSD), or nephrolithiasis, is a growing global health concern characterized by the formation of crystalline calculi within the urinary tract. This review provides a comprehensive overview of the multifactorial etiology of KSD, encompassing metabolic abnormalities, genetic predisposition, dietary habits, microbial influences, and environmental factors. The pathogenesis involves urinary supersaturation, crystal nucleation, oxidative stress, inflammation, and biofilm formation, with a key role played by Randall’s plaques and immune responses. Genetic polymorphisms in calcium and phosphate transport genes further increase susceptibility. Risk factors such as inadequate hydration, high oxalate intake, and metabolic disorders are explored alongside age- and sex-specific variations. Global warming, occupational heat exposure, and urbanization are also linked to increased stone incidence. Diagnostic advances include low-dose and dual-energy CT, AI-based stone prediction models, and 24-hour urine analysis. Innovations in treatment, such as laser lithotripsy, robotic ureteroscopy, and mHealth tools, are enhancing outcomes. Preventive strategies—centered on dietary modifications, adequate fluid intake, and pharmacological agents like thiazides and citrate—play a pivotal role in reducing recurrence. The disease’s impact on renal function and quality of life emphasizes the need for early intervention and personalized care. This review underscores the importance of multidisciplinary approaches for effective KSD management.