Pathophysiological and Physicochemical Basis of Ammonium Urate Stone Formation in Dolphins
IAAAM 2014
Cynthia R. Smith1*; John R. Poindexter2; Jennifer M. Meegan1; I. Alexandru Bobulescu2; Eric D. Jensen3; Stephanie Venn-Watson1; Khashayar Sakhaee2
1National Marine Mammal Foundation, San Diego, CA, USA; 2Department of Internal Medicine and Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3U.S. Navy Marine Mammal Program, Space and Naval Warfare Systems Center Pacific, San Diego, CA, USA

Abstract

Nephrolithiasis has been increasingly reported in managed bottlenose dolphins, with all published cases to date being ammonium urate nephrolithiasis.1,2 A critical need exists to better understand the urinary environment in dolphins in order to develop appropriate treatment and prevention strategies for nephrolithiasis. A case-control study was conducted in managed dolphins with and without evidence of nephrolithiasis. Dolphins were sampled in both fasting and postprandial states in order to study the effect of dietary factors on serum and urinary biochemistry. Urine was continuously collected over a 6-h period via urinary catheter and divided into three 2-hour collections, with a substantial fish meal given after completion of the first collection. Blood was sampled at the beginning of the fasting period and end of the postprandial period. There were no significant differences in serum and urine chemistries and acid-base profiles between dolphins with and without stones, at baseline or postprandially, suggesting that case and control animals in this study represent a continuum of stone risk. In analyses combining the case and control dolphins in a single cohort, we noted significant postprandial increases in urinary uric acid, sulfate and net acid excretion, accompanied by increased urinary ammonium excretion and urine pH. The supersaturation index of ammonium urate increased postprandially by more than twofold. These findings suggest that dolphins are susceptible to ammonium urate nephrolithiasis, due in part to a high dietary load of acid and purines, which results in a transient but marked increase in the urinary supersaturation of ammonium urate salt.

Acknowledgments

The authors are grateful to the Office of Naval Research for funding this work (ONR Award N000141110203). Special thanks to Sacha Stevenson, Celeste Parry, Veronica Cendejas, Mark Baird, and Dr. Carolina Le-Bert for their technical support of this project. We also thank Randall Dear, Elaine Allen, Brenda Bauer, and DruAnn Price for their training expertise.

* Presenting author

Literature Cited

1. Venn-Watson S, Smith CR, Daniels R, Townsend F. Clinical relevance of urate nephrolithiasis in bottlenose dolphins (Tursiops truncatus). Dis Aqua Org. 2010;89:167–177.

2. Smith CR, Venn-Watson S, Wells RS, Johnson SP, Maffeo N, Balmer BC, Jensen ED. Comparison of nephrolithiasis prevalence in two bottlenose dolphin (Tursiops truncatus) populations. Front Endocrinol. 2013;4:145.

Speaker Information
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Cynthia R. Smith
National Marine Mammal Foundation
San Diego, CA, USA


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