CALCIUM-OXALATE INTERATION IN MODULATING CALCIUM OXALATE STONE FORMATION

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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.