UROLITHIASIS: EXPERIMENTAL MODELS, ETIOPATHOGENESIS, AND SCREENING APPROACHES FOR DRUG EVALUATION

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  Dhanenjay Roy, Sanuj Muralidharan, Atul Kabra

• Dhanenjay Roy, Sanuj Muralidharan, Atul Kabra
• UROLITHIASIS: EXPERIMENTAL MODELS, ETIOPATHOGENESIS, AND SCREENING APPROACHES FOR DRUG EVALUATION

Abstract

Urolithiasis, the pathological formation of crystalline deposits within the urinary tract, remains a prevalent global health concern with significant clinical and socio-economic impact. Its multifactorial etiopathogenesis involves complex interactions between genetic predisposition, metabolic abnormalities, dietary influences, and environmental factors, leading to various stone types such as calcium oxalate, calcium phosphate, uric acid, and cystine. This review consolidates current understanding of epidemiology, causative mechanisms, and experimental screening strategies for antiurolithiatic agents, with particular focus on in vivo animal models and in vitro methodologies. Widely employed experimental models include ethylene glycol, sodium oxalate, glyoxylate, hydroxy-L-proline, diet-induced protocols, zinc-disc implantation, and infection-mediated struvite formation, each reproducing specific aspects of stone pathogenesis. We detail the mechanisms underlying these models, standard induction protocols, and their respective strengths and limitations in reflecting human disease. Emerging approaches such as microfluidic organ-on-chip platforms, integration of genomics and metabolomics (“omics”), and advanced imaging technologies offer enhanced physiological relevance and real-time monitoring capabilities. However, translational challenges persist, notably the variability between animal and human urinary biochemistry, ethical considerations, and lack of standardized evaluation criteria. Addressing these gaps will require harmonized methodologies and more representative models integrating host–microbiome interactions and personalized metabolic profiles. By synthesizing conventional and innovative experimental strategies, this review aims to serve as a practical reference for researchers and clinicians, facilitating informed model selection and robust experimental design in the ongoing quest to identify and develop effective antiurolithiatic therapies.