Calcium oxalate stone formation in genetic hypercalciuric stone-forming rats
Calcium oxalate stone formation in genetic hypercalciuric stone-forming rats
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DOI：
10.1046/j.1523-1755.2002.00190.x
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发表时间：
2002-03-01
影响因子：
19.6
通讯作者：
Coe, FL
中科院分区：
文献类型：
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作者：
Bushinsky, DA;Asplin, JR;Coe, FL
背景经过54代，我们已经成功培育出一种最大化尿钙排泄的大鼠。这些大鼠现在持续排泄8至10倍于对照组的钙，均匀地形成结晶不良的磷酸钙肾结石，并被称为遗传性高钙尿石形成（GHS）大鼠。这些大鼠被用来测试的假设，增加尿草酸排泄不仅会增加相对于草酸钙固相的过饱和度，而且会增加草酸钙与磷酸钙过饱和度的比率，并导致草酸钙结石形成。为了增加尿草酸盐排泄，在雄性GHS大鼠的饮食中加入草酸盐前体羟脯氨酸。GHS大鼠分别饲喂含钙1.2%的标准饲料或含1%、3%和5%反式-4-羟基-L-脯氨酸（羟脯氨酸）的标准饲料。在GHS大鼠的饮食中添加1%的羟脯氨酸导致尿草酸排泄增加，这并没有随着提供额外的羟脯氨酸而进一步增加。添加1%和3%羟脯氨酸不改变钙排泄，而提供5%羟脯氨酸导致尿钙排泄减少。添加1%羟脯氨酸导致尿草酸钙过饱和度增加，但没有进一步增加羟脯氨酸。加入1%和3%羟脯氨酸并没有改变尿中磷酸氢钙的过饱和度，而加入5%羟脯氨酸则倾向于降低这种过饱和度。与对照组和3%羟脯氨酸组相比，添加5%羟脯氨酸可增加草酸钙过饱和度与磷酸钙过饱和度的比值。几乎所有的老鼠都形成了结石。对照组和1%羟脯氨酸组结石均由钙和磷酸盐（磷灰石）组成，3%羟脯氨酸组结石由磷灰石和草酸钙组成，5%羟脯氨酸组结石均为草酸钙。向GHS大鼠提供额外的膳食羟脯氨酸增加尿草酸盐排泄、草酸钙过饱和和草酸钙与磷酸钙过饱和的比率，导致草酸钙肾结石的形成。因此，通过添加一种常见的氨基酸，GHS大鼠现在不仅模拟了肾结石患者中发现的最常见的代谢异常，高钙尿症，而且形成了最常见的肾结石类型，草酸钙。
Background. Over 54 generations, we have successfully bred a strain of rats that maximizes urinary calcium excretion. The rats now consistently excrete 8 to 10 times as much calcium as controls, uniformly form poorly crystalline calcium phosphate kidney stones, and are termed genetic hypercalciuric stone-forming (GHS) rats. These rats were used to test the hypothesis that increasing urinary oxalate excretion would not only increase the supersaturation with respect to the calcium oxalate solid phase, but also would increase the ratio of calcium oxalate-to-calcium phosphate supersaturation and result in calcium oxalate stone formation.Methods. To increase urine oxalate excretion an oxalate precursor, hydroxyproline, was added to the diet of male GHS rats. The GHS rats were fed a standard 1.2% calcium diet alone or with 1%, 3% or 5% trans-4-hydroxy-L-proline (hydroxyproline).Results. The addition of 1% hydroxyproline to the diet of GHS rats led to in increase in urinary oxalate excretion, which did not increase further with the provision of additional hydroxyproline. The addition of 1% and 3% hydroxyproline did not alter calcium excretion while the provision of 5% hydroxyproline led to a decrease in urine calcium excretion. The addition of 1% hydroxyproline led to an increase in urinary calcium oxalate supersaturation, which did not further increase with additional hydroxyproline. The addition of 1% and 3% hydroxyproline did not alter urinary supersaturation with respect to calcium hydrogen phosphate while the addition of 5% hydroxyproline tended to lower this supersaturation. Compared to rats fed the control and the 3% hydroxyproline diet the addition of 5% hydroxyproline increased the ratio of calcium oxalate supersaturation to calcium phosphate supersaturation. Virtually all rats formed stones. In the control and 1% hydroxyproline group, all of the stones were composed of calcium and phosphate (apatite), in the 3% hydroxyproline group the stones were a mixture of apatite and calcium oxalate, while in the 5% hydroxyproline group all of the stones were calcium oxalate.Conclusions. The provision of additional dietary hydroxyproline to GHS rats increases urinary oxalate excretion, calcium oxalate supersaturation and the ratio of calcium oxalate-to-calcium phosphate supersaturation, resulting in the formation of calcium oxalate kidney stones. Thus, with the addition of a common amino acid, the GHS rats now not only model the most common metabolic abnormality found in patients with nephrolithiasis, hypercalciuria, but form the most common type of kidney stone, calcium oxalate.