CALCIUM-OXALATE INTERACTION IN MODULATION OF STONE FORMATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该项目解决了最近引起相当大兴趣的一个主题，即饮食钙限制要么无效，要么可能会夸大结石形成的可能性。这种担忧的基础是发生在肠道和尿液中的所谓草酸钙相互作用。我们是最早描述肠道中草酸钙相互作用的人之一，即肠道中钙与草酸盐结合后尿中草酸盐排泄的变化。在低钙摄入时，没有足够的腔内钙结合草酸，增加草酸吸收和尿草酸。在AH患者中，尿草酸可轻度-中度升高，因为肠道钙吸收的增加导致钙结合草酸的量不足。高钙摄入有望消除或减轻尿草酸盐的升高。限制因素是饮食中的草酸含量，因为正是饮食中的草酸与腔内钙结合。该成分旨在阐明“钙-草酸相互作用”，即钙通过在肠道中结合草酸影响尿中总草酸的量，以及通过草酸络合影响尿中离子草酸的量。通过这一过程，限钙可以增加尿草酸，减弱尿中草酸钙饱和度的下降，这可能是由于尿钙的下降而引起的。相反，高钙摄入可以降低尿中总草酸盐和离子草酸盐，与尿中钙增加可能引起的尿中草酸钙饱和度升高相反。要检验的总体假设是，钙与草酸盐的相互作用取决于饮食中草酸盐的限制、肠道对钙的吸收状态或高钙尿的程度，以及钙是作为食物还是补充剂提供的。本部分的目标是完成检验上述假设所需的剩余研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project addresses a topic that has raised considerable interest recently, dealing with the possibility that dietary calcium restriction is either ineffective or may exaggerate stone formation. The basis for this concern is the so-called calcium-oxalate interaction that occurs in the bowel and in urine. We were among the first to describe oxalate-calcium interaction in the bowel, i.e., changes in urinary oxalate excretion from binding of oxalate by calcium in the intestinal tract. During low calcium intake, there is inadequate luminal calcium to bind oxalate, increasing oxalate absorption and urinary oxalate. In AH, urinary oxalate may be mild-moderately increased, because increased intestinal absorption of calcium leaves insufficient amount of calcium to bind oxalate. A high calcium intake would be expected to eliminate or attenuate the rise in urinary oxalate. The limiting factor is dietary oxalate content, since it is dietary oxalate that is bound by luminal calcium. This component is directed at elucidating the "calcium-oxalate interaction", a process by which calcium affects the amount of total oxalate in urine by binding oxalate in the intestinal tract, as well as the amount of ionic oxalate in urine by complexing oxalate. By this process, calcium restriction could increase urinary oxalate, attenuating the decline in urinary saturation of calcium oxalate that might ensue from the fall in urinary calcium. Conversely, a high calcium intake could lower total and ionic oxalate in urine, opposing the rise in urinary saturation of calcium oxalate that might occur from increased urinary calcium. The overall hypothesis to be tested is that calcium-oxalate interaction is dependent on dietary oxalate restriction, the state of intestinal absorption of calcium or the degree of hypercalciuria, and on whether calcium is provided as food or supplement. The objective of this component is to complete remaining studies required to test the above hypothesis.