NOVEL TREATMENT FOR CYSTINURIA AND STONES OF IMMOBILIZATION

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The overall goal of this project is to determine whether a new thiol compound (Rimatil) would be more effective and safer than Thiola in controlling cystinuria and cystine stone formations, and to ascertain if a new diphosphonate (alendronate) might prevent stone formation from prolonged immobilization. A dose response relation will be characterized in order to show that Rimatil is more effective than Thiola in lowering cystine excretion. A 3 yr. randomized trial between Rimatil and Thiola will be conducted in cystinuric patients, with the dose of each adjusted to achieve an optimum control of cystine excretion (250-400 mg/day). Endpoints will be drug dosage and side effect profile, with the expectation that Rimatil group would require a lower dose and improved safety of usage. Using bedrest model, stone formation during prolonged immobilization (or space flight) has been shown to be due to increased renal excretion of calcium and phosphate from bone loss. Alendronate might prevent the rise in urinary calcium and phosphate (and in urinary saturation of stone-forming calcium salts) by inhibiting bone resorption. This scheme will be tested in normal subjects undergoing 3 weeks of bedrest at Dallas and those participating in a 17-week bedrest study at Houston. These studies have biomedical importance, since they may allow improved treatment of cystinuria, and lead to the development of an effective countermeasure for stone-formation during space travel and other immobilization states.