Role of Anion Transporter SLC26A6 (CFEX) in Prevention of Hyperoxaluria and Urolithiasis

Abstract

In the proximal tubule of the kidney, a significant fraction of Cl− is transported by apical membrane Cl−‐formate exchange and Cl−‐oxalate exchange. Studies to identify the transporter(s) mediating apical membrane Cl−‐anion exchange in the proximal tubule led to the characterization of CFEX (SLC26A6). Functional expression of CFEX in Xenopus oocytes demonstrated that the transporter is capable of mediating multiple modes of anion exchange including Cl−‐oxalate exchange. Comparison of wild‐type and CFEX null mice with respect to transport in renal brush border vesicles and microperfused tubules demonstrated that CFEX primarily mediates Cl−‐oxalate exchange rather than Cl−‐formate exchange in the proximal tubule in vivo. CFEX null mice were observed to have a high incidence of calcium oxalate urolithiasis that was attributable to hyperoxaluria. Hyperoxaluria in CFEX null mice was found to result from a defect in oxalate secretion in the intestine, thereby causing increased net absorption of ingested oxalate and elevated plasma oxalate concentration. Thus, by mediating intestinal oxalate secretion, CFEX plays an essential role in preventing hyperoxaluria and calcium oxalate nephrolithiasis.