CALCIUM-OXALATE INTERATION IN MODULATING CALCIUM OXALATE STONE FORMATION

本部分的目的是阐明“钙-草酸盐相互作用”，这是一个膳食钙通过结合肠道中的草酸盐、减少吸收的草酸盐量和通过络合减少尿离子草酸盐来影响尿草酸盐的过程。总的假设是，钙-草酸盐相互作用取决于饮食中的草酸盐、肠道钙吸收的状态以及钙作为食物或补充剂的输送。 在目的1中，我们的目的是证明正常受试者的钙-草酸相互作用发生在自由，但不限制草酸盐摄入。我们的假设是，尿草酸盐的下降将对抗与钙补充相关的尿钙的上升，使尿草酸钙饱和度的变化最小化。在这项由安慰剂和碳酸钙阶段组成的2阶段随机交叉试验中，10名维持代谢性饮食的正常受试者将在每个阶段的最后2天采集两份24小时尿液标本。在目的2中，我们的目的是证明钙-草酸相互作用在吸收性高钙尿症（AH）状态下比正常肠道钙吸收更大。在一项2期随机交叉试验中，我们将在16名接受代谢性饮食的AH患者中测试在草酸盐限制期间补充碳酸钙与安慰剂的效果。我们预计草酸钙尿饱和度会有适度但显著的增加，但程度低于正常受试者。在目标3中，我们的目标是表明，由于食物中潜在的保护性营养素的相互作用，作为食物提供的钙比作为补充剂提供的钙促进更少的钙-草酸盐相互作用。从一个2阶段的随机交叉研究中进行的10个正常受试者维持低或高钙饮食与自由草酸盐摄入量，我们预计在高钙饮食期间，由于尿草酸盐的下降，尿草酸钙饱和度的衰减上升。在目的4中，我们检验了当限制草酸盐时，草酸钙饱和度依赖于尿钙浓度的假设。使用来自完成门诊评价的患者登记研究的数据，计算在随机和限制饮食下收集的24小时尿液中草酸钙的尿RSR，并与AH-I、AH-II和正常尿钙患者组中相应的尿钙和草酸盐浓度相关。

The objective of this component is to elucidate the "calcium-oxalate interaction", a process by which dietary calcium affects urinary oxalate by binding oxalate in the intestine, reducing the amount of absorbed oxalate, and by reducing urinary ionic oxalate through complexation. The overall hypothesis is that calcium-oxalate interaction is dependent on dietary oxalate, the state of intestinal calcium absorption and on the delivery of calcium as food or supplement. In Aim 1, our objective is to demonstrate that for normal subjects calcium-oxalate interaction occurs during a liberal, but not restricted oxalate intake. Our hypothesis is that the decline in urinary oxalate will oppose the rise in urinary calcium associated with calcium supplementation, minimizing the change in urinary saturation of calcium oxalate. In this 2-phase randomized crossover trial comprised of placebo and calcium carbonate phases, 10 normal subjects maintained on a metabolic diet will collect two 24-hour urine specimens on the last 2 days of each phase. In Aim 2, our objective is to demonstrate that calcium-oxalate interaction is exaggerated in states of absorptive hypercalciuria (AH) compared with normal intestinal calcium absorption. In a 2-phase randomized crossover trial, we will test the effect of calcium carbonate supplementation versus placebo during oxalate restriction in 16 AH patients on a metabolic diet. We expect a modest but significant increase in urinary saturation of calcium oxalate, to a lesser degree than seen in normal subjects. In Aim 3, our objective is to show that calcium delivered as food promotes less calcium-oxalate interaction than calcium delivered as a supplement due to the interaction of potentially protective nutrients in food. From a 2-phase randomized crossover study conducted in 10 normal subjects maintained on a low or a high calcium diet with a liberal oxalate intake, we expect an attenuated rise in urinary saturation of calcium oxalate during a high calcium diet due to a decline in urinary oxalate. In Aim 4, we test the hypothesis that saturation of calcium oxalate is dependent on urinary calcium concentration when oxalate isrestricted. Using data from a registry of patients who completed an ambulatory evaluation, the urinary RSR of calcium oxalate derived from 24-hour urines collected on random and restricted diets will be calculated and correlated with corresponding urinary calcium and oxalate concentrations in AH-I, AH-II and normocalciuric patient groups.