Abstract: SA-PO1036
SLC26A6 Mediates Enteric Oxalate Secretion in CKD
Session Information
- Water/Urea/Vasopressin, Organic Solutes
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Fluid, Electrolytes, and Acid-Base
- 702 Water/Urea/Vasopressin, Organic Solutes
Authors
- Neumeier, Laura Isabella, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Thomson, Robert Brent, Yale University School of Medicine, New Haven, Connecticut, United States
- Eckardt, Kai-Uwe, University Hospital Charite Berlin, Berlin, Germany
- Aronson, Peter S., Yale University School of Medicine, New Haven, Connecticut, United States
- Knauf, Felix, University Hospital Charite Berlin, Berlin, Germany
Background
A state of oxalate equilibrium is maintained in patients with healthy kidney function. However, as GFR declines plasma oxalate levels start to rise. Upregulation of oxalate secretion in the colon of rats with CKD has been described in the past, yet the molecular identification of the oxalate transporter(s) involved has yet to be defined. Hence, we examined whether oxalate transporter SLC26A6 contributes to the extrarenal clearance of oxalate via the gut in CKD.
Methods
CKD was induced by injecting age- and gender-matched 129S6 (wild-type) and Slc26a6-/- mice with aristolochic acid. Renal function was monitored by changes in plasma creatinine sampled retro-orbitally. Intestinal SLC26A6 was assessed by qPCR and western blot analysis. Mice were maintained on an oxalate-free diet and plasma and fecal oxalate levels were measured enzymatically using an oxalate oxidase assay.
Results
SLC26A6 mRNA and protein expression were greatly increased in colon of mice with CKD. However, expression levels of glucose (SGLT-1) and amino acid transporters (CAT-1), other representative intestinal transport processes, did not differ in colon of CKD mice. In line with these findings, fecal oxalate excretion was increased in mice with CKD. In contrast, fecal oxalate excretion was reduced and plasma oxalate levels significantly increased in Slc26a6-/- mice as compared with wild-type mice.
Conclusion
In summary, we demonstrate that SLC26A6-mediated enteric oxalate secretion is critical in decreasing the body burden of oxalate in CKD.
Funding
- Private Foundation Support