Effects of Oral Administration of Citrate, Thiazide, Allopurinol and Magnesium on Renal Calcium Oxalate Crystal Formation and Osteopontin Expression in a Rat Urolithiasis Model / 대한비뇨기과학회지

ABSTRACT

PURPOSE: It has previously been reported that citrate, thiazide, allopurinol and magnesium (CTAM) have inhibitory effects on calcium oxalate crystallization, but the effects of CTAM on the matrix proteins of stones in vivo has not been studied. Using an ethylene glycol-induced urolithiasis model, we investigated the effects of CTAM on renal crystallization and the expression of osteopontin (OPN), which is an important stone matrix protein. MATERIALS AND METHODS: Adult Sprague-Dawley rats (200-250gm) were divided randomly into 6 groups of 10 rats. Group 1 was left untreated, and served as a control. Group 2 (CID group) was fed 0.8% ethylene glycol and 1% ammonium chloride (crystal-inducing diet, CID) in drinking water for 4 weeks. Groups 3, 4, 5 and 6 (CTAM groups) were fed the same CID as group 2, but were also treated with either potassium citrate or hydrochlorothiazide or allopurinol or magnesium hydroxide, for 4 weeks, respectively. We biochemically analyzed the 24-hour urine and serum samples. The renal calcium content was measured by atomic absorption. The kidneys were histologically examined for crystal deposit with HandE staining, and for OPN expression with immunohistochemical staining. RESULTS: The grade of calcium oxalate crystal deposits, and renal calcium content, were significantly decreased in the CTAM groups compared to the CID group, which also correlated with the decreased expression of OPN proteins in the kidneys of the CTAM-treated rats. CTAM were all effective in preventing calcium oxalate crystal formation, and decreasing the expression of OPN in rat kidneys. CONCLUSIONS: Our results suggest that CTAM are effective in preventing calcium oxalate stone formation, and that OPN plays an important role in calcium oxalate nephrolithiasis.