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The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

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Abstract

The intestine exerts a considerable influence over urinary oxalate in two ways, through the absorption of dietary oxalate and by serving as an adaptive extra-renal pathway for elimination of this waste metabolite. Knowledge of the mechanisms responsible for oxalate absorption and secretion by the intestine therefore have significant implications for understanding the etiology of hyperoxaluria, as well as offering potential targets for future treatment strategies for calcium oxalate kidney stone disease. In this review, we present the recent developments and advances in this area over the past 10 years, and put to the test some of the new ideas that have emerged during this time, using human and mouse models. A key focus for our discussion are the membrane-bound anion exchangers, belonging to the SLC26 gene family, some of which have been shown to participate in transcellular oxalate absorption and secretion. This has offered the opportunity to not only examine the roles of these specific transporters, revealing their importance to oxalate homeostasis, but to also probe the relative contributions made by the active transcellular and passive paracellular components of oxalate transport across the intestine. We also discuss some of the various physiological stimuli and signaling pathways which have been suggested to participate in the adaptation and regulation of intestinal oxalate transport. Finally, we offer an update on research into Oxalobacter formigenes, alongside recent investigations of other oxalate-degrading gut bacteria, in both laboratory animals and humans.

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Acknowledgements

The authors wish to thank Tara Braun, Kristina Fernandez, Heran Getachew, Shreya Mishra, Candi Morris, Susie Robertson and Tisha Van Pelt who provided valuable technical assistance and animal husbandry over the period spanning the collection of data presented here. We are also grateful to Dr. Robert W. Freel, who performed some of the experiments reported and for many useful discussions on epithelial oxalate transport and the transporters involved. This work, and the data presented herein, has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grants DK-056245, DK-081624, DK-088892 to M. Hatch, and U54 DK-083908 (sub-award to J. M. Whittamore), from the National Institutes of Health, together with funding from the Oxalosis and Hyperoxaluria Foundation.

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  1. Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA

    Jonathan M. Whittamore & Marguerite Hatch

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  1. Jonathan M. Whittamore
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  2. Marguerite Hatch
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Correspondence to Jonathan M. Whittamore.

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All procedures involving animals were performed under protocols approved by the University of Florida Institutional Animal Care and Use Committee (IACUC), in accordance with the National Institutes of Health “Guide for the Care and Use of Laboratory Animals”.

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Whittamore, J.M., Hatch, M. The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man. Urolithiasis 45, 89–108 (2017). https://doi.org/10.1007/s00240-016-0952-z

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  • DOI: https://doi.org/10.1007/s00240-016-0952-z

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