title: Chronic metabolic acidosis reduces urinary oxalate excretion and promotes intestinal oxalate secretion in the rat.
abstract: Urinary oxalate excretion is reduced in rats during a chronic metabolic acidosis, but how this is achieved is not clear. In this report, we re-examine our prior work on the effects of a metabolic acidosis on urinary oxalate handling [Green et al., Am J Physiol Ren Physiol 289(3):F536-F543, 2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal oxalate transport. Sprague-Dawley rats were provided with 0.28 M ammonium chloride in their drinking water for either 4 or 14 days followed by 24 h urine collections, blood-gas and serum ion analysis, and measurements of (14)C-oxalate fluxes across isolated segments of the distal colon. Urinary oxalate excretion was significantly reduced by 75% after just 4 days compared to control rats, and this was similarly sustained at 14 days. Oxalate:creatinine clearance ratios indicated enhanced net re-absorption of oxalate by the kidney during a metabolic acidosis, but this was not associated with any substantive changes to serum oxalate levels. In the distal colon, oxalate transport was dramatically altered from net absorption in controls (6.20 ± 0.63 pmol cm(-2) h(-1)), to net secretion in rats with a metabolic acidosis (-5.19 ± 1.18 and -2.07 ± 1.05 pmol cm(-2) h(-1) at 4 and 14 days, respectively). Although we cannot rule out modifications to bi-directional oxalate movements along the proximal tubule, these findings support a gut-kidney axis in the management of oxalate homeostasis, where this shift in renal handling during a metabolic acidosis is associated with compensatory adaptations by the intestine.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA. jwhittamore@ufl.edu.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Whittamore
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Hatch
mesh_terms: D000138:Acidosis / Q000097:blood / Q000652:urine*; D000818:Animals; D002118:Calcium / Q000097:blood; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003404:Creatinine / Q000652:urine; D008297:Male; D010070:Oxalates / Q000097:blood / Q000652:urine*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D002712:Chlorides; D010070:Oxalates; D003404:Creatinine; D002118:Calcium
keywords: Acid–base; Ammonium chloride; Anion exchange; Colon; Kidney; Ussing chamber