Bushinsky D A
Department of Medicine, University of Rochester School of Medicine and Dentistry, NY, USA.
Semin Nephrol. 1996 Sep;16(5):448-57.
In humans, idiopathic hypercalciuria is associated with stone formation. To study the mechanisms that are responsible for the excess urine calcium excretion in ways that are difficult to impossible in humans, we have developed a rat model of idiopathic hypercalciuria. Hypercalciuric rats were successively inbred for more than 40 generations to produce a strain in which urine calcium excretion is far greater than that of controls and all rats form kidney stones. Analysis of the model has revealed that the rats not only exhibit increased intestinal calcium absorption but an independent defect in renal tubular resorption and an increased tendency for bone demineralization. These findings closely parallel those in patients with idiopathic hypercalciuria. In the intestine, bone, and kidney there is an increased number of vitamin D receptors which appear to make the rats more sensitive to the effect of 1,25(OH)2D3. Whether the increased number of vitamin D receptors can be directly translated into hypercalciuria and whether the same abnormality is present in humans with idiopathic hypercalciuria remains to be determined.
在人类中，特发性高钙尿症与结石形成有关。为了以在人类中难以或无法实现的方式研究导致尿钙排泄过多的机制，我们建立了一种特发性高钙尿症大鼠模型。高钙尿症大鼠连续近亲繁殖40多代，以培育出一个品系，该品系大鼠的尿钙排泄量远高于对照组，且所有大鼠都会形成肾结石。对该模型的分析表明，这些大鼠不仅表现出肠道钙吸收增加，还存在肾小管重吸收的独立缺陷以及骨脱矿化倾向增加。这些发现与特发性高钙尿症患者的情况极为相似。在肠道、骨骼和肾脏中，维生素D受体数量增加，这似乎使大鼠对1,25(OH)2D3的作用更加敏感。维生素D受体数量增加是否能直接导致高钙尿症，以及特发性高钙尿症患者是否存在相同的异常情况，仍有待确定。
