Urolithiasis is a common disease in industrialized nations. About 8–15% of the population of Europe and North America develop renal stones in their lifetime. 80% of these kidney stones consist of calcium salts and usually occur as calcium oxalate. Elevation of urinary calcium oxalate concentration is the major risk factor for nephrolithiasis. Oxalate is ingested from food or synthesized in the liver and excreted in the kidneys but only about 10% of urine oxalate derives from nutrition. Oxalate is the final product from glyoxylate metabolism in the liver.

Sulfate-anion-transporter-1, sat-1, is a sulfate-oxalate-bicarbonate-exchanger localized in the sinusoidal membrane of hepatocytes as well as in the basolateral membrane of proximal tubule cells. To determine sat-1 transport mechanisms we performed experiments with sat-1 expressing Xenopus laevis oocytes. Trans-stimulation experiments show that sat-1 exchanges sulfate, oxalate and bicarbonate bidirectionally. Under physiological concentrations of sulfate (0.3 mM) and bicarbonate (25 mM), oxalate uptake is reduced by 70 4% and 95 1%, respectively. Simultaneous application of sulfate and bicarbonate nearly abolishes oxalate uptake. Sat-1 in the kidneys probably exchanges bicarbonate against sulfate. In addition, chloride affects sat-1 sulfate transport. [³⁵S]Efflux decreases by 38 8% in the absence of chloride in the medium while sulfate uptake is also reduced in the absence of chloride. Besides the kidneys, sat-1 is also localized in the sinusoidal membrane of hepatocytes where it probably exchanges oxalate against sulfate. To characterize sat-1 in the liver, the impact of oxalate precursors, glyoxylate and glycolate, on sulfate uptake by sat-1 was tested. Neither glyoxylate nor glycolate inhibit sulfate transport but glyoxylate trans-stimulates sulfate uptake.

HepG2 cells are an established model for oxalate metabolism and they produce sat-1 mRNA as revealed by RT-PCR. These cells were used to investigate the effect of different substrates from oxalate metabolism on sat-1 mRNA expression by real-time PCR. HepG2 cells were incubated for 4 days in glycine, hydroxyproline, oxalate, glyoxylate, and glycolate. Sat-1 mRNA expression was upregulated by glyoxylate indicating its contribution to nephrolithiasis.