Question: The epidemiological incidence of nephrolithiasis is higher in men than in women. Most urinary stones consist of oxalate, which is largely synthesized in the liver and then released into the systemic circulation by the sulfate-oxalate exchanger, sat1. In the kidney proximal tubules, oxalate is excreted via a two-step process that includes uptake from the blood by the contraluminal sat1 and release into the urine by the luminal chloride-formate/oxalate exchanger, CFEX. The role of sat1 and CFEX in development of oxalate nephrolithiasis is unclear. Methodology: The ethylene glycol (EG) model of nephrolithiasis in male (M) and female (F) rats was used to induce oxaluric state, and to study the expression of sat1, CFEX, and rate-limiting enzymes of oxalate synthesis, alcohol dehydrogenase (Adh1) and hydroxyacid oxidase (Hao1), by real-time PCR and immunochemical methods. Result: As compared to controls, the EG-treated rats exhibited: (a) strong oxalosis and oxaluria (M>F), (b) increased abundance of sat1 protein, but not mRNA, in liver and kidneys of F rats only, (c) unchanged expression of CFEX mRNA, as well as (d) marginally changed expression of Adh1 and Hao1 mRNA in organs of both sexes. Conclusion: Despite hyperoxaluria, protein expression of sat1 in M and CFEX in both sexes was sufficient to handle the increased concentrations of oxalate induced by EG, indicating their limited role in oxalate nephrolithiasis.

Fundamental medical sciences