Revealing the molecular landscape of calcium oxalate renal calculi utilizing a tree shrew model: a transcriptomic analysis of the kidney.

Abstract

Our comprehensive genomic investigation employing tree shrew calcium oxalate stone models unveils intricate links between kidney stone formation and diverse physiological systems. We identify a constellation of genes whose expression patterns point to multifaceted interactions among cardiovascular health, renal fibrosis, and bone homeostasis in the pathogenesis of renal calculi. Key players include CHIT1, TNFRSF18, CLEC4E, RGS1, DCSTAMP, and SLC37A2, which emerge as pivotal actors in arteriosclerosis, renal fibrosis, and osteoclastogenesis respectively, showcasing the complexity of stone disease. The downregulation of ADRA1D, LVRN, and ABCG8 underscores roles in urodynamics, epithelial-mesenchymal transition, and vitamin D metabolism, linking these to nephrolithiasis. Comparative genomics across tree shrew, human (Randall's plaque), rat, and mouse identifies shared KEGG pathways including Calcium signaling, Actin cytoskeleton regulation, Neuroactive ligand-receptor interactions, Complement and coagulation cascades, TRP channel regulation by inflammatory mediators, p53 signaling, and Fc gamma R-mediated phagocytosis. These pathways underscore the interconnectedness of immune, inflammatory, and metabolic processes in stone development. Our findings suggest novel targets for future therapeutics and prevention strategies against nephrolithiasis, highlighting the need for a holistic view of the disease encompassing multiple pathogenic factors.