From History to Innovation: Pathophysiology and the Evolving Landscape of Urolithiasis Diagnosis and Treatment

Urolithiasis is a multicomponent illness described by the production of calcified stones within the urinary tract. It remains an important global health issue due to its frequency, recurrence, and cost. Urine supersaturation, crystal nucleation, development, aggregation, and retention are all steps in the stone formation process that are influenced by environmental, genetic, and metabolic factors. Calcium oxalate and calcium phosphate account for the majority of cases, whereas uric acid or infection stones develop in the context of particular metabolic or infectious conditions. Breakthroughs in molecular science have uncovered mechanisms such as crystal adhesion, oxidative stress, inflammation, and tubular injury, advancing understanding of disease development. The identification of genetic variants in transporters and metabolic enzymes by genetic studies shows hereditary susceptibility. Innovative diagnostics such as Dual-Energy Computed Tomography (DECT), ultra-low-dose imaging, and machine learning now enable accurate non-invasive characterisation of stones. Technologies like Fourier-Transform Infrared (FTIR), Raman, and micro-spectroscopy, complemented by intraoperative sampling, also facilitate enhanced stone composition analysis. Treatment modalities have evolved from traditional pharmacologic agents like citrate, thiazides, and allopurinol to emerging drugs that target molecular pathways of nucleation and aggregation. New precision-based therapies and innovative formulations are designed to reduce recurrence and enhance outcomes. The future direction focuses on incorporating molecular diagnostics, genomics, and artificial intelligence into practice for individualised management. This review discusses the mechanisms, classification, molecular and genetic determinants, and therapeutic breakthroughs in urolithiasis, emphasising the transition from conventional to emerging approaches and indicating future directions for better patient care.