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Oxalate transport by the mouse intestine in vitro is not affected by chronic challenges to systemic acid–base homeostasis

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Abstract

In rats, we recently showed how a chronic metabolic acidosis simultaneously reduced urinary oxalate excretion and promoted oxalate secretion by the distal colon leading to the proposition that acid–base disturbances may trigger changes to renal and intestinal oxalate handling. The present study sought to reproduce and extend these observations using the mouse model, where the availability of targeted gene knockouts (KOs) would offer future opportunities to reveal some of the underlying transporters and mechanisms involved. Mice were provided with a sustained load of acid (NH4Cl), base (NaHCO3) or the carbonic anhydrase inhibitor acetazolamide (ATZ) for 7 days after which time the impacts on urinary oxalate excretion and its transport by the intestine were evaluated. Mice consuming NH4Cl developed a metabolic acidosis but urinary oxalate was only reduced 46% and not statistically different from the control group, while provision of NaHCO3 provoked a significant 2.6-fold increase in oxalate excretion. For mice receiving ATZ, the rate of urinary oxalate excretion did not change significantly. Critically, none of these treatments altered the fluxes of oxalate (or chloride) across the distal ileum, cecum or distal colon. Hence, we were unable to produce the same effects of a metabolic acidosis in mice that we had previously found in rats, failing to find any evidence of the ‘gut-kidney axis’ influencing oxalate handling in response to various acid–base challenges. Despite the potential advantages offered by KO mice, this model species is not suitable for exploring how acid–base status regulates oxalate handling between the kidney and intestine.

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Acknowledgements

The authors wish to thank Maureen Mohan for excellent technical assistance and animal husbandry.

Funding

This work was supported by NIH grants DK108755 and DK088892 to M. Hatch, and an Experimental Pathology Innovative Grant from the Department of Pathology, Immunology and Laboratory Medicine in the UF College of Medicine to J. Whittamore.

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  1. Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, PO Box 100275, 1600 SW Archer Rd, Gainesville, FL, 32610, USA

    Jonathan M. Whittamore & Marguerite Hatch

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Correspondence to Jonathan M. Whittamore.

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All experimental procedures were undertaken in accordance with the ethical standards of the University of Florida Institutional Animal Care and Use Committee (IACUC) and the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Whittamore, J.M., Hatch, M. Oxalate transport by the mouse intestine in vitro is not affected by chronic challenges to systemic acid–base homeostasis. Urolithiasis 47, 243–254 (2019). https://doi.org/10.1007/s00240-018-1067-5

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