Current Strategies for Diagnosis, Treatment, Management and Prevention of Renal Calculi in Bottlenose Dolphins (Tursiops truncatus)…What We’ve Learned and Where We’re Headed
2018 Joint EAZWV/AAZV/Leibniz-IZW Conference
Jenny Meegan1, DVM, DACZM; John R. Poindexter2; Khashayar Sakhaee2, MD; Carolina Le-Bert1, DVM; Shawn Johnson3, DVM; Stephanie Venn-Watson1, DVM, MPH; Amanda J. Ardente4, DVM, PhD; Roger L. Sur5, MD; Eric Jensen6, DVM; Sam Ridgway1, DVM, PhD, DACZM; Cynthia R. Smith1, DVM
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; 3The Marine Mammal Center, Sausalito, CA, USA; 4Ardente Veterinary Nutrition LLC, Gainesville, FL, USA; 5University of California San Diego, La Jolla, CA, USA; 6US Navy Marine Mammal Program, SSC Pacific, San Diego, CA, USA

Abstract

Bottlenose dolphins (Tursiops truncatus) under human care are susceptible to ammonium urate (NH4U) kidney stone formation. Kidney stone disease in dolphins can cause significant morbidity attributed to azotemia, hematuria, renal obstruction, reduced renal function, and renal failure.15 Diagnosis and quantification of kidney stones in bottlenose dolphins is best achieved using a combination of ultrasound and computed tomography (CT).7,9 CT with IV contrast as well as renal scintigraphy have been successfully utilized to assess renal perfusion, function and renal obstructions in dolphins.7,10

Medical management of cases with partial ureteral obstruction has recently been accomplished with aggressive fluid support and low-dose tamsulosin.8 If the problem worsens or complete obstruction develops, surgical intervention may be required. Surgical intervention of ureteral obstruction has been successfully performed using laser lithotripsy in two adult female dolphins.6,8,12 In male dolphins, ureteroscopy has not been successful due to the unique urethral anatomy, including an extreme curvature and excessive length.12

Recent investigations of ammonium urate stone solubility combined with challenges associated with allopurinol therapy suggest that stone dissolution may not be possible in dolphins.3 Instead, current therapy is aimed at managing clinical evidence of disease and preventing future stone formation. Hydration therapy is important to increase urine production, subsequently decrease saturation of urine crystals, and improve renal azotemia.14 Additionally, various formulations of potassium-citrate and sodium-citrate have been administered orally, aiming to alkalinize the urine with limited success.13,15,16

Comprehensive studies of both free-ranging and managed dolphin populations have been conducted to identify risk factors for stone formation, revealing differences in urinary physicochemistry and renal stone prevalence.4,9,11 The risk for NH4U stone formation in dolphins may be due, in part, to a marked increase in urinary ammonium (NH4+), uric acid, and pH following a large fish meal, thus creating a favorable urinary environment for the precipitation of NH4U salt.9 Further, nutrient analyses of fish species comprising the diets of free-ranging versus managed dolphin populations have also revealed differences in key nutrients, including mineral cation and anion concentrations and purine content, which may increase the risk of stone formation in managed dolphins.1,2 Recent modified diet feeding trials, targeting a lower purine composition and acid-ash content, have demonstrated a dietary impact on improving urinary risk factors, implicating the role of nutrition in the pathophysiology of stone formation.5

Current best practices for management of kidney stone disease in dolphins consist of a combination of hydration, diet, and treatment aimed to alkalinize the urine and reduce the risk factors associated with stone formation. Further dietary and treatment optimization is currently underway.

Acknowledgments

We acknowledge the ONR grants that supported this work (N00014-15-1-2131 and N00014-15-1-2327). The authors also sincerely thank all of the veterinarians, technicians, trainers, and research team members who assisted in acquiring the samples and data for this project.

Literature Cited

1.  Ardente AJ, Garrett TJ, Colee J, Vagt BJ, Walsh MT, Wells RS, Smith CR, Jensen ED, Schmitt TL, Hill RC. Differences in purine metabolite concentrations in the diet of managed and free-ranging common bottlenose dolphins (Tursiops truncatus). Aquat Mammals. 2017b;43(6):618–628.

2.  Ardente AJ, Wells RS, Smith CR, Walsh MT, Jensen ED, Schmitt TL, Colee J, Hill RC. Dietary cation-anion difference may explain why ammonium urate nephrolithiasis occurs more frequently in common bottlenose dolphins (Tursiops truncatus) under human care than in free-ranging common bottlenose dolphins. J Anim Sci. 2017a;95:1396–1406.

3.  Argade S, Smith CR, Shaw T, Zupkas P, Schmitt TL, Venn-Watson S, Sur RL. Solubility of ammonium acid urate nephroliths from bottlenose dolphins (Tursiops truncatus). J Zoo Wildl Med. 2013;44(4):853–858.

4.  Le-Bert CR, Smith CR, Poindexter J, Ardente A, Meegan J, Wells RS, Venn-Watson S, Jensen ED, Sakhaee K. (In press.) Comparison of potential dietary and urinary risk factors for ammonium urate nephrolithiasis in two bottlenose dolphin (Tursiops truncatus) populations. Ren Physiol.

5.  Meegan JM, Poindexter JR, Sakhaee K, Baird M, Parry C, Le-Bert C, Ardente AJ, Jensen ED, Venn-Watson S, Smith CR. Dietary effects on urinary physicochemistry in a managed population of bottlenose dolphins (Tursiops truncatus). Proc Int Assoc Aquat Anim Med. 2017.

6.  Schmitt TL, Sur RL. Treatment of ureteral calculus obstruction with laser lithotripsy in an Atlantic bottlenose dolphin (Tursiops truncatus). J Zoo Wildl Med. 2012;43(1):101–109.

7.  Smith CR, Johnson SP, Cassle SE, Jensen ED, Hoh CK, Venn-Watson SK. Predicting renal health with diagnostic imaging in bottlenose dolphins. Proc Int Assoc Aquat Anim Med, Rome, Italy; 2008:13–14.

8.  Smith CR, Meegan JM, Bailey J, Scott GN, Sur R, L’Esperance J, Ivančić M, Cotte LS, Cendejas V, Sakhaee K, Ridgway SH, Jensen ED. Case report: surgical management of a partial ureteral obstruction under general anesthesia in a geriatric bottlenose dolphin. Proc Int Assoc Aquat Anim Med; 2015.

9.  Smith CR, Poindexter JR, Meegan JM, Bobulescu IA, Jensen ED, Venn-Watson S, Sakhaee K. Pathophysiological and physicochemical basis of ammonium urate stone formation in dolphins. J Urol. 2014;192(1):260–266.

10.  Smith CR, Solano M, Johnson SP, Venn-Watson SK, Jensen ED, Hoh CK. Renal scintigraphy in nine bottlenose dolphins using technetium-99m mercaptoacetyltriglycine (99mTC-MAG3). Proc ACVR; 2010:57.

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

12.  Sur RL, Woo JR, Meegan JM, Smith CR, Schmitt T, L’Esperance J, Hendrikson D. (In press) Surgical management of nephrolithiasis in the bottlenose dolphin: collaborations between the urologist and veterinarian. J Endourol Case Reports.

13.  Townsend FI, Ridgway S. Kidney stones in Atlantic bottlenose dolphins (Tursiops truncatus): composition, diagnosis and therapeutic strategies. Proc Int Assoc Aquat Anim Med; 1995:2.

14.  Türk C, Petřík A, Sarica K, Seitz C, Skolarikos A, Straub M, Knoll T. EAU guidelines on diagnosis and conservative management of urolithiasis. Eur Urol. 2016;69(3):468–474.

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

16.  Venn-Watson SK, Townsend FI, Daniels RL, Sweeney JC, McBain JW, Klatsky LJ, Hicks CL, Staggs LA, Rowles TK, Schwacke LH, Wells RS, Smith CR. Hypocitraturia in common bottlenose dolphins (Tursiops truncatus): assessing a potential risk factor for urate nephrolithiasis. Comp Med. 2010b;60(2):149–153.

 

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Jenny Meegan, DVM, DACZM
National Marine Mammal Foundation
San Diego, CA, USA


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