Chronic metabolic acidosis reduces urinary oxalate excretion and promotes intestinal oxalate secretion in the rat

Urolithiasis. 2015 Nov;43(6):489-99. doi: 10.1007/s00240-015-0801-5. Epub 2015 Jul 11.


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2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal oxalate transport.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.

Keywords: Acid–base; Ammonium chloride; Anion exchange; Colon; Kidney; Ussing chamber.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis / blood
  • Acidosis / urine*
  • Animals
  • Calcium / blood
  • Chlorides / metabolism
  • Colon / metabolism*
  • Creatinine / urine
  • Male
  • Oxalates / blood
  • Oxalates / urine*
  • Random Allocation
  • Rats, Sprague-Dawley


  • Chlorides
  • Oxalates
  • Creatinine
  • Calcium