Clinical relevance of urate nephrolithiasis in bottlenose dolphins Tursiops truncatus

Abstract

Few cases of nephrolithiasis (renal calculi) have been reported in bottlenose dolphinsTursiops truncatus. A case-control study was conducted to compare ultrasonographic images and clinicopathologic serum and urine values among 14 dolphins with nephrolithiasis (mild cases: 1 to 19 nephroliths, n = 8; advanced cases: ≥20 nephroliths, n = 6) to 6 controls over an 18 mo period. Archived nephroliths collected postmortem from 7 additional bottlenose dolphins were characterized using quantitative analysis. All advanced cases had bilateral nephroliths, and 67% had visible collecting ducts. During the study, 2 of the advanced cases developed hydronephrosis, and 1 of these cases had ureteral obstruction due to a nephrolith. Compared to controls, cases (mild and advanced) were significantly more likely to have anemia (hematocrit [HCT] < 38%), high blood urea nitrogen (> 59 mg dl ). Advanced-case urine samples were more likely to have erythrocytes, occult blood, and lower pH compared to mild cases and controls. Mean serum uric acid among all study groups was low (0.15 to 0.27 mg dl -1 ). Urinary uric acid concentrations were highest among mild cases (272 mg g -1 creatinine), but advanced cases had levels lower than that of controls (40 and 127 mg g -1 creatinine, respectively). All nephroliths were characterized as 100% ammonium acid urate. We conclude that nephrolithiasis is clinically relevant in dolphins and can decrease renal function and HCT. The presence of nephrolithiasis, presumably ammonium acid urate nephrolithiasis, in the face of low serum uric and relatively low urinary uric acid in advanced cases may indicate a metabolic syndrome similar to that reported in humans. (Ulrich et al. 1996). The reference laboratory also observed the samples for the presence of xanthine using infrared spectroscopy (Ulrich et al. 1996).Ultrasound evaluations and study population definitions. Both kidneys from 20 dolphins were evaluated and total nephrolith counts were estimated using at least 1 renal ultrasound examination during the study period. A Voluson i portable ultrasound machine with a 2 to 5 MHz 4D transducer (RAB2-5-RS; General Electric Healthcare) was used to capture images of the kidneys. Ultrasound evaluation using B-mode with tissue harmonic imaging included (1) nephrolith identification and quantification, and (2) measurement of the collecting duct if it was visible. Collecting-duct measurements were only included if color Doppler ultrasound confirmed that the image was a collecting duct and not a vessel. To evaluate kidneys for the presence of nephroliths, cine loops of each kidney were captured in both the longitudinal and transverse planes and then reviewed with OsiriX imaging software (open source; www.osirix-viewer.com). Nephroliths were identified as hyperechoic foci within the kidney that created acoustic shadowing and were quantitated for a total nephrolith count per kidney (see Fig. 1). We did not use color or power Doppler to look for twinkling artifact as an identifier of nephroliths in our study...

Effects of Freeze-Thaw Cycle on Urine Values from Bottlenose Dolphins (Tursiops truncatus)

“…Our study demonstrated an increase in urinary uric acid, though not after correcting for creatinine, when comparing fresh and frozen-thawed samples. Interestingly, our study population has a high prevalence of ammonium acid urate nephrolithiasis (Venn-Watson et al, 2010a). Follow-up research is needed to assess the need for diluting frozen urine samples for accurate uric acid levels.…”

“…Marine mammal urine samples are used to assess renal health, characterize osmoregulation, determine reproductive cycles, assess potential effects of ecosystem contaminants, and detect marine (Ortiz, 2001;Gulland et al, 2002;Roebeck et al, 2005;Venn-Watson et al, 2010a, 2010b. This study focused on the use of comprehensive urinalyses to study individual animal and population renal health.…”

“…Bottlenose dolphins (Tursiops truncatus) are susceptible to urate nephrolithiasis, and urinalyses are being used to identify risk factors for nephrolith formation (Venn-Watson et al, 2010a, 2010b. Retrospective and population studies may require that urinalyses be performed on frozen samples that have been stored for various periods of time.…”

Adipose-Derived Stem Cell Collection and Characterization in Bottlenose Dolphins (Tursiops truncatus)

“…Veterinarians can now also consider stem cell therapy when evaluating the treatment options for common dolphin diseases such as corneal trauma and liver disease, both of which have shown promising therapeutic benefits with stem cell treatment in humans [31,32]. Several dolphin diseases have similar human counterparts, including type 2 diabetes [8], urate nephrolithiasis with renal failure [33], and iron overload with liver disease [9,34]. The dolphin may serve as a human model for several disease processes, as was recently proposed for type 2 diabetes [10] and aging studies [35], where new treatment modalities using stem cells could be realized.…”

Pathophysiological and Physicochemical Basis of Ammonium Urate Stone Formation in Dolphins

“…Ammonium urate (NH 4 U) nephrolithiasis associated with morbidity has been reported in managed bottlenose dolphins ( Tursiops truncatus ), but research efforts evaluating the pathophysiological and physicochemical mechanisms of nephrolithiasis in dolphins have been limited 1, 2 .…”