Chlorthalidone with potassium citrate decreases calcium oxalate stones and increases bone quality in genetic hypercalciuric stone-forming rats.
Chlorthalidone with potassium citrate decreases calcium oxalate stones and increases bone quality in genetic hypercalciuric stone-forming rats.
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DOI：
10.1016/j.kint.2020.12.023
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发表时间：
2021-05
影响因子：
19.6
通讯作者：
Bushinsky DA
中科院分区：
文献类型：
--
作者：
Krieger NS;Asplin J;Granja I;Chen L;Spataru D;Wu TT;Grynpas M;Bushinsky DA
为了研究人类特发性高钙尿症，我们开发了一种动物模型，遗传性高钙尿症结石形成大鼠，其病理生理学与人类特发性高钙尿症相似。喂食草酸盐前体羟脯氨酸后，该模型中的每只大鼠都会形成草酸钙结石。使用这种大鼠模型，我们测试了氯噻酮和柠檬酸钾联合使用是否会减少草酸钙结石的形成并改善骨质量。将113代大鼠随机分为4组：对照组、柠檬酸钾组、氯噻酮+氯化钾组和柠檬酸钾+氯噻酮组，每组113只，饲以含羟脯氨酸的正常钙磷饲料。在第6周、第12周和第18周收集尿液，并测定肾结石形成和骨骼参数。与氯化钾相比，柠檬酸钾降低尿钙，氯噻酮进一步降低尿钙，柠檬酸钾加氯噻酮进一步降低尿钙。与所有其他组相比，柠檬酸钾加氯噻酮可降低尿草酸。各组间草酸钙过饱和度无显著差异。柠檬酸钾和氯噻酮都不能改变结石形成。然而，柠檬酸钾加氯噻酮显着减少结石形成。氯噻酮和枸橼酸钾加氯噻酮组椎体骨小梁增加。氯噻酮组皮质骨面积增加，但柠檬酸钾或柠檬酸钾+氯噻酮组无此作用。骨小梁的力学性能与氯噻酮改善，但没有柠檬酸钾加氯噻酮。因此，在遗传性高尿钙结石形成大鼠喂养的饮食导致草酸钙结石形成，柠檬酸钾加氯噻酮防止结石形成优于任何一种药物单独。单独使用氯噻酮可改善骨质量，但添加柠檬酸钾没有提供额外的益处。
To study human idiopathic hypercalciuria we developed an animal model, genetic hypercalciuric stone-forming rats, whose pathophysiology parallels that of human idiopathic hypercalciuria. Fed the oxalate precursor, hydroxyproline, every rat in this model develops calcium oxalate stones. Using this rat model, we tested whether chlorthalidone and potassium citrate combined would reduce calcium oxalate stone formation and improve bone quality more than either agent alone. These rats (113 generation) were fed a normal calcium and phosphorus diet with hydroxyproline and divided into four groups: diets plus potassium chloride as control, potassium citrate, chlorthalidone plus potassium chloride, or potassium citrate plus chlorthalidone. Urine was collected at six, 12, and 18 weeks and kidney stone formation and bone parameters were determined. Compared to potassium chloride, potassium citrate reduced urinary calcium, chlorthalidone reduced it further and potassium citrate plus chlorthalidone even further. Potassium citrate plus chlorthalidone decreased urine oxalate compared to all other groups. There were no significant differences in calcium oxalate supersaturation in any group. Neither potassium citrate nor chlorthalidone altered stone formation. However, potassium citrate plus chlorthalidone significantly reduced stone formation. Vertebral trabecular bone increased with chlorthalidone and potassium citrate plus chlorthalidone. Cortical bone area increased with chlorthalidone but not potassium citrate or potassium citrate plus chlorthalidone. Mechanical properties of trabecular bone improved with chlorthalidone, but not with potassium citrate plus chlorthalidone. Thus in genetic hypercalciuric stone-forming rats fed a diet resulting in calcium oxalate stone formation, potassium citrate plus chlorthalidone prevented stone formation better than either agent alone. Chlorthalidone alone improved bone quality, but adding potassium citrate provided no additional benefit.
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DOI：
10.1038/nrneph.2016.101
发表时间：
2016-09
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Coe FL;Worcester EM;Evan AP
通讯作者：
Evan AP
影响因子：
6.6
作者：
Ferraro, Pietro Manuel;Ticinesi, Andrea;Gambaro, Giovanni
通讯作者：
Gambaro, Giovanni
影响因子：
13.6
作者：
Asplin, John R.;Donahue, Susan E.;Bushinsky, David A.
通讯作者：
Bushinsky, David A.
影响因子：
19.6
作者：
Bushinsky, DA;Asplin, JR;Coe, FL
通讯作者：
Coe, FL
影响因子：
6.2
作者：
Karnauskas, AJ;van Leeuwen, JPTM;Favus, MJ
通讯作者：
Favus, MJ