Kazumi Yamaguchi

Effects of Magnesium Salts in Preventing Experimental Oxalate Urolithiasis in Rats

Magnesium oxide, magnesium hydroxide, magnesium sulfate, magnesium trisilicate, and magnesium citrate were added to a calcium-oxalate lithogenic diet in order to determine their effects in preventing lithogenesis. Male Wistar-strain rats which had been fed the glycolic-acid diet developed marked urinary calculi within four weeks. Rats in the magnesium-hydroxide, magnesium-citrate, and magnesium-trisilicate groups, however, had almost no stones in the urinary system. Rats in the magnesium-oxide and magnesium-sulfate groups showed significantly less effect than those in the former three groups. During the experimental period, the 24-hour urinary oxalate excretion and concentration were higher in the glycolic-acid group than in the other groups. The urinary citrate excretion and concentration were the highest in the magnesium-hydroxide and magnesium-citrate groups and higher in the magnesium-trisilicate and magnesium-oxide groups than in the magnesium-sulfate and glycolic-acid groups. Similar trends were observed in the urinary magnesium excretion and in its concentration. The urinary calcium excretion and concentration were higher in the experimental groups than in the glycolic-acid group. The urinary calcium/magnesium ratio remained mostly unchanged. Therefore, it can be concluded that alkaline magnesium salts increase the urinary calcium and magnesium concentrations, without changing the calcium/magnesium ratio, and inhibit urinary calculi formation, most likely by increasing the urinary citrate concentration.

Determination of Urinary Citrate by Ion Chromatography

Ion chromatography was used to determine urinary citrate concentration. The technique is simple, requiring a 100-fold dilution of urine and 35 minutes at most for each analysis. The technique does, however, have the disadvantage that it requires a rather expensive automated system. The minimum detectable limit for citrate was 0.5 microgram/ml. in a standard solution, and the regression line for the standard curve from 0.5 to 50 micrograms/ml. citrate had a significant correlation coefficient (lnY = 1.048 X lnX-2.755, r = 0.997). The intra-run coefficient of variation was 0.9 per cent. The overall intra-run and inter-run coefficients of variation, including the sampling and dilution of urine, were 4.8 and 8.3 per cent respectively. There is a possibility that another ion is close enough to the citrate peak to interfere; however, this problem can be solved by the treatment of the sample with citrate lyase. When the present method was compared with the conventional enzyme method, a significant correlation between the results was obtained in both human and rat urine. The 24-hour urinary citrate excretion in eight normal human males was 73.8 to 378.4 mg./day (mean, 174.7 mg./day), while that in male Wistar-strain rats (approximately 150 gm.) was 1.5 to 18.6 mg./day (mean, 9.5 mg./day), as measured in more than 50 consecutive rat urine samples.

Effects of pyruvate salts, pyruvic acid, and bicarbonate salts in preventing experimental oxalate urolithiasis in rats

Sodium pyruvate, potassium pyruvate, pyruvic acid, sodium bicarbonate and potassium bicarbonate were added to a calcium-oxalate lithogenic diet (a glycolic-acid diet) in order to determine their effects in preventing lithogenicity. Male Wistar-strain rats who had been fed the glycolic-acid diet developed marked urinary calculi within four weeks. Rats in the sodium and potassium pyruvate groups had, however, almost no stones in the urinary system. Rats in the bicarbonate and pyruvic-acid groups showed slightly less effect than those in the pyruvate groups. Urinary oxalate excretion was high in all the groups during the experiment. The urinary oxalate concentration was relatively higher in the sodium-pyruvate group, and significantly higher in the potassium-pyruvate group, than in the glycolic-acid group. Urinary citrate excretion was high both in the pyruvate and bicarbonate groups; the urinary citrate concentration was, however, significantly higher in the pyruvate groups than in the bicarbonate groups at the fourth experimental week. The urinary calcium and magnesium concentrations were irrelevant to the diets administered. Therefore, it can be concluded that pyruvate salts inhibit urinary calculi formation, not by decreasing oxalate synthesis, but by increasing the urinary citrate concentration; bicarbonate salts work in the same manner, but a little less effectively.

[Effects of malate, succinate and bicarbonate salts in preventing experimental oxalate urolithiasis in rats].

Kazumi Yamaguchi, Yoshihide Ogawa, Makoto Morozumi, Tohru Tanaka and Ryuichi Kitagawa Department of Urology, School of Medicine, Juntendo University, Tokyo, Japan (Director: Prof. R. Kitagawa) Sodium malate, malic acid, sodium succinate, succinic acid, and sodium bicarbonate were added to a calcium-oxalate lithogenic diet (a glycolic-acid diet) in order to determine their effects in preventing lithogenicity. Male Wistar-strain rats who had been fed the glycolic-acid diet developed marked urinary calculi within 4 weeks. Rats in the sodium malate and succinate groups had, however, almost no stones in the urinary system. Rats in the bicarbonate, malic-acid and succinic-acid groups showed less effect than those in the malate and succinate groups. Urinary oxalate excretion was high in all the groups during the experiment. Urinary citrate excretion was high in the malate, succinate and bicarbonate groups, but low in the malic-acid, succinic-acid, and glycolic-acid groups; the urinary citrate concentration was relatively higher in the malate and succinate groups than in the bicarbonate group, especially towards the end of the experiment. The urinary calcium and magnesium concentrations were unrelated to the diets administered. Therefore, it can be concluded that sodium malate and succinate inhibit urinary calculi formation by increasing the urinary citrate concentration; bicarbonate works in the same manner, but a little less effectively; malic acid and succinic acid have no such effect.