The incidence of calcium oxalate nephrolithiasis in the US has been increasing throughout the past three decades. Biopsy studies show that both calcium oxalate nephrolithiasis and nephrocalcinosis probably occur by different mechanisms in different subsets of patients. Before more-effective medical therapies can be developed for these conditions, we must understand the mechanisms governing the transport and excretion of oxalate and the interactions of the ion in general and renal physiology. Blood oxalate derives from diet, degradation of ascorbate, and production by the liver and erythrocytes. In mammals, oxalate is a terminal metabolite that must be excreted or sequestered. The kidneys are the primary route of excretion and the site of oxalate's only known function. Oxalate stimulates the uptake of chloride, water, and sodium by the proximal tubule through the exchange of oxalate for sulfate or chloride via the solute carrier SLC26A6. Fecal excretion of oxalate is stimulated by hyperoxalemia in rodents, but no similar phenomenon has been observed in humans. Studies in which rats were treated with C-14- oxalate have shown that less than 2% of a chronic oxalate load accumulates in the internal organs, plasma, and skeleton. These studies have also demonstrated that there is interindividual variability in the accumulation of oxalate, especially by the kidney. This Review summarizes the transport and function of oxalate in mammalian physiology and the ion's potential roles in nephrolithiasis and nephrocalcinosis.
