Vol. 7, Issue 2, Part C (2025)

Kidney-stone disease (nephrolithiasis) has transitioned from a surgical oddity to one of the fastest-growing non-communicable disorders, accounting for an estimated 67 million new symptomatic episodes and 1.3 million disability-adjusted life-years in 2021. Incidence is accelerating under the combined pressures of global warming, dietary Westernisation and population ageing, yet nearly half of the burden is theoretically preventable. This state-of-the-art review distils evidence published between 2019 and mid-2025 across epidemiology, pathogenesis, risk stratification and management, and maps a future research agenda. We first trace the striking geographic and demographic heterogeneity of nephrolithiasis, highlighting a latitude-linked “stone belt” where crude annual incidence now exceeds 600 cases per 100 000 and prevalence approaches 15 per cent. Although men still account for most cases, sex parity is emerging as metabolic syndrome fuels uric-acid calculi in post-menopausal women. Economic modelling places annual U.S. expenditures near USD 9 billion, and disease-specific quality-of-life decrements rival those of chronic back pain. Pathogenesis is framed as a continuum: urinary supersaturation and heterogeneous nucleation give rise to crystal growth, aggregation and retention on Randall’s plaques or ductal plugs, which are then amplified by oxidative-stress and inflammasome pathways. Crystal modulators such as citrate, magnesium, osteopontin and uromodulin counterbalance promoters including oxalate and urate. Multi-omics studies implicate CLDN14-mediated calcium handling, SLC26A6-dependent oxalate secretion and gut-microbiome dysbiosis as pivotal levers in stone initiation. Risk-factor analysis covers metabolic derangements, diet, dehydration, obesity, comorbidities, medications and special states such as childhood, pregnancy and spinal-cord injury. Universal prevention begins with urine-volume targets (≥ 2.5 L day⁻¹) and pH modulation, then escalates to dietician-guided counselling and pharmacologic prophylaxis thiazide diuretics, potassium citrate, allopurinol, cystine-binding thiols and, more recently, sodium-glucose cotransporter-2 inhibitors. Digital health tools, Bluetooth-enabled water bottles and wearable hydration sensors have demonstrated 30-45 per cent improvements in adherence. Management of acute stone events emphasises non-steroidal anti-inflammatory analgesia, α-blocker-based expulsive therapy and prompt decompression for sepsis or solitary-kidney obstruction. A tiered surgical approach shock-wave lithotripsy, thulium-fibre laser ureteroscopy, mini- and micro-percutaneous nephrolithotomy, retrograde intrarenal surgery and occasional robotic pyelolithotomy achieves stone-free rates exceeding 90 per cent with progressively lower morbidity. Emerging fronts include urine-proteome panels with AUROC > 0.90, polygenic-risk scores that reclassify one-quarter of patients, microbiome engineering with oxalate-degrading consortia, AI-driven recurrence prediction and nano-scale citrate or enzyme carriers capable of dissolving calculi in situ. Key knowledge gaps involve biomarker validation, microbiome causality, AI generalisability, nanomedicine safety and equitable implementation. By integrating molecular discovery with behavioural nudging and minimally invasive technology, kidney-stone care can shift from episodic surgery to precision prevention transforming a painful, recurrent disorder into a largely avoidable condition.