Development of prophylaxis by the elucidation of the pathogenesis in the initial urinary stone formation

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(1) Renal tubular cell injury induced by oxidative stress via mitochondrial collapse is said to be the initial step of urinary stone formation. We elucidated that mitochondrial permeability transition pore opening, which is blocked by cyclosporine A, is associated with mitochondrial collapse, oxidative stress, and activation of apoptotic pathway in the initial steps of renal calcium crystallization. New medicines for urolithiasis prevention are expected to target this mechanism. (2) The mechanism of urinary stone formation in the obesity and metabolic syndrome environment involves the progression of an inflammation and immunoresponse, including oxidative stress and adhesion reactions in renal tissues. (3) Genome-wide association studies show that 5q35.3, 7p14.3, and 13q14.1 in Japanese are associated with urolithiasis. Thus, SNP analysis would aid in the prediction of urolithiasis risk and recurrence.