Characterization of renal NaCl and oxalate transport in Slc26a6^−/− mice

Abstract

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.

Sodium Oxalate-Induced Acute Kidney Injury Associated With Glomerular and Tubulointerstitial Damage in Rats

“…Intestinal oxalate absorption is predominantly passive and paracellular. In addition, transcellular transport of oxalate is mediated by SLC26 anion exchangers expressed on both apical and basolateral membranes of intestinal epithelial cells ( Efe et al, 2019 ; Knauf et al, 2019 ). In healthy humans, the plasma oxalate levels are fairly low (1–6 μmol/L) ( Kasidas and Rose, 1986 ; Hoppe et al, 2009 ).…”

“…In healthy humans, the plasma oxalate levels are fairly low (1–6 μmol/L) ( Kasidas and Rose, 1986 ; Hoppe et al, 2009 ). Oxalate is primarily excreted by the kidneys via glomerular filtration and tubular secretion, the last one being mediated by the SLC26A anion exchanger expressed in the basolateral membrane ( Robijn et al, 2011 ) and the Cl – /oxalate exchanger SLC26A6 expressed mainly in the brush-border membrane of proximal tubule cells ( Bergsland et al, 2011 ; Knauf et al, 2019 ) and in the apical membrane of distal nephron cells ( Kujala et al, 2005 ).…”

Critically ill, tubular injury, delayed early recovery: characteristics of acute kidney disease with renal oxalosis

“…SLC26A6−/−knockout mice showed a prominent increase in blood and urinary oxalate levels, supporting the notion that renal tubular damage in S 3 might induce subsequent hyperoxalemia and hyperoxaluria. SLC26A6 down-regulation yet weakens the inhibitory effect on the activity of the coupled citrate transporter NaDC-1, contributing to hypocitraturia that renders oxalate more likely to form crystals in urine [ 23 ].…”

Severe Oxalosis Secondary to Acute Kidney Disease Contributes to Delayed Early Recovery of Renal Function

“…NaDC-1, resulting in hypocitraturia that renders oxalate more likely to form crystals in urine [19].…”