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2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal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