Characterization of renal NaCl and oxalate transport in Slc26a6 -/- mice.

The apical membrane Cl ^- /oxalate exchanger SLC26A6 has been demonstrated to play a role in proximal tubule NaCl transport based on studies in microperfused tubules. The present study is directed at characterizing the role of SLC26A6 in NaCl homeostasis in vivo under physiological conditions. Free-flow micropuncture studies revealed that volume and Cl ^- absorption were similar in surface proximal tubules of wild-type and Slc26a6 ^-/- mice. Moreover, the increments in urine flow rate and sodium excretion following thiazide and furosemide infusion were identical in wild-type and Slc26a6 ^-/- mice, indicating no difference in NaCl delivery out of the proximal tubule. The absence of an effect of deletion of SLC26A6 on NaCl homeostasis was further supported by the absence of lower blood pressure in Slc26a6 ^-/- compared with wild-type mice on normal or low-salt diets. Moreover, raising plasma and urine oxalate by feeding mice a diet enriched in soluble oxalate did not affect mean blood pressure. In contrast to the lack of effect of SLC26A6 deletion on NaCl homeostasis, fractional excretion of oxalate was reduced from 1.6 in wild-type mice to 0.7 in Slc26a6 ^-/- mice. We conclude that, although SLC26A6 is dispensable for renal NaCl homeostasis, it is required for net renal secretion of oxalate.