Bushinsky D A, Grynpas M D, Nilsson E L, Nakagawa Y, Coe F L
Nephrology Unit, University of Rochester, New York, USA.
Kidney Int. 1995 Dec;48(6):1705-13. doi: 10.1038/ki.1995.468.
Our genetic hypercalciuric (GH) rats have been selected and inbred for 29 generations to maximize urine calcium (UCa) excretion compared to identical gender controls (Ctl). To determine the effect of the increased UCa on urinary supersaturation and stone formation, we pair fed 15 GH and 15 Ctl rats a standard 1.2% calcium diet for 18 weeks, measured urine supersaturation every two weeks, and examined the urinary tract of 1/3 of the rats for the presence of stones every six weeks. Any stones formed were studied by SEM, X-ray and electron diffraction and X-ray microanalysis. Over the entire study UCa was increased in the GH compared to Ctl, resulting in greater supersaturation with respect to calcium hydrogen phosphate (CaHPO4) at all times and calcium oxalate (CaOx) at most times. There was a progressive increase in the incidence of stone formation in GH rats with one of five rats having stones at six weeks, three of five with stones at 12 weeks and five of five with stones at 18 weeks. There were no stones formed in Ctl rats. SEM reveals discrete stones and not nephrocalcinosis. X-ray and electron diffraction and X-ray microanalysis reveal the stones to be poorly crystalline apatite which is a solid phase of calcium and phosphate. Compared to Ctl, in the GH rats the saturation ratio for CaHPO4 increased proportionally more than that for CaOx, perhaps explaining why the rats formed apatite and not oxalate stones. This is the first description of an animal model of spontaneous nephrolithiasis.
我们的遗传性高钙尿症（GH）大鼠已经经过29代的选育和近亲繁殖，与相同性别的对照大鼠（Ctl）相比，其尿钙（UCa）排泄量达到最大化。为了确定UCa增加对尿液过饱和度和结石形成的影响，我们对15只GH大鼠和15只Ctl大鼠进行配对饲养，给予标准的1.2%钙饮食，持续18周，每两周测量一次尿液过饱和度，每六周检查1/3大鼠的尿路是否存在结石。对形成的任何结石进行扫描电子显微镜（SEM）、X射线和电子衍射以及X射线微分析研究。在整个研究过程中，与Ctl相比，GH大鼠的UCa增加，导致始终相对于磷酸氢钙（CaHPO4）以及大多数时候相对于草酸钙（CaOx）有更高的过饱和度。GH大鼠结石形成的发生率逐渐增加，6周时五只大鼠中有一只出现结石，12周时五只中有三只出现结石，18周时五只全部出现结石。Ctl大鼠未形成结石。SEM显示为离散的结石而非肾钙质沉着症。X射线和电子衍射以及X射线微分析显示结石为结晶不良的磷灰石，它是钙和磷酸盐的固相。与Ctl相比，在GH大鼠中，CaHPO4的饱和比增加的比例比CaOx更多，这可能解释了为什么大鼠形成的是磷灰石结石而非草酸钙结石。这是对自发性肾结石动物模型的首次描述。
