Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter
Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter
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DOI：
10.1152/ajprenal.00620.2007
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发表时间：
2008-05-01
影响因子：
4.2
通讯作者：
Glenton, Patricia A.
中科院分区：
文献类型：
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作者：
Khan, Saeed R.;Glenton, Patricia A.
关于特发性肾结石发病机制的最常见理论认为，肾脏内磷酸钙 (CaP) 的沉淀对于该疾病的发展至关重要。我们决定检验 CaP 底物可以促进草酸钙 (CaOx) 在肾脏中沉积的假设。通过给敲除 (KO) NaP(i) IIa (Npt2a)（一种钠磷酸盐协同转运蛋白）的雄性小鼠喂食乙醛酸，诱导实验性高草酸尿症。 Npt2a KO 小鼠尿钙过多，并在肾小管中产生 CaP 沉积。实验性高草酸尿症导致高钙尿症 KO 小鼠和正常尿钙对照 B6 小鼠出现 CaOx 结晶尿。只有 KO 小鼠的肾脏中产生 CaOx 晶体沉积物，但 CaOx 晶体与 CaP 沉积物分开沉积。也许 CaP 沉积物无法用于 CaOx 过度生长。这些结果还验证了早期动物模型观察结果，该观察结果表明 CaP 底物对于 CaOx 的肾脏沉积不是必需的，并且可能涉及其他因素，例如局部过饱和。尽管存在极度高草酸尿症，但 B6 小鼠体内没有 CaOx 沉积，这也表明钙和草酸盐在 CaOx 肾结石发展中的重要性。
The most common theories about the pathogenesis of idiopathic kidney stones consider precipitation of calcium phosphate (CaP) within the kidneys critical for the development of the disease. We decided to test the hypothesis that a CaP substrate can promote the deposition of calcium oxalate (CaOx) in the kidneys. Experimental hyperoxaluria was induced by feeding glyoxylate to male mice with knockout (KO) of NaP(i) IIa (Npt2a), a sodium-phosphate cotransporter. Npt2a KO mice are hypercalciuric and produce CaP deposits in their renal tubules. Experimental hyperoxaluria led to CaOx crystalluria in both the hypercalciuric KO mice and the normocalciuric control B6 mice. Only the KO mice produced CaOx crystal deposits in their kidneys, but the CaOx crystals deposited separately from the CaP deposits. Perhaps CaP deposits were not available for a CaOx overgrowth. These results also validate earlier animal model observations that showed that CaP substrate is not required for renal deposition of CaOx and that other factors, such as local supersaturation, may be involved. The absence of CaOx deposition in the B6 mice despite extreme hyperoxaluria also signifies the importance of both calcium and oxalate in the development of CaOx nephrolithiasis.