Urate Urolithiasis and Hyperuricosuria in a Weimaraner, Secondary to the SLC2A9 Transporter Defect Jodi L
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Downloaded from vetrecordcasereports.bmj.com on May 15, 2014 - Published by group.bmj.com Veterinary Record Case Reports COMPANION OR PET ANIMALS Urate urolithiasis and hyperuricosuria in a Weimaraner, secondary to the SLC2A9 transporter defect Jodi L. Westropp,1 Eric G. Johnson,2 Mark C. Fuller,2 Noa Safra,3 Danika L. Bannasch3 1Department of Medicine and SUMMARY veterinarian for decreased appetite, vomiting and Epidemiology, School of In this case, we describe a middle-aged, male lethargy. On physical examination the dog was febrile Veterinary Medicine, University of California-Davis, One Shields Weimaraner that presented with upper and lower urinary (41.1°C (106.0°F)). A urinalysis revealed the presence Avenue, Davis, CA 95616,USA tract urate urolithiasis. The dog required surgical of pyuria, although a urine culture was not per- 2Department of Surgical and intervention to remove the obstruction in the right ureter formed. An abdominal ultrasound identified small Radiological Sciences, School as well as medical management to prevent recurrent ureteroliths in the proximal right ureter, and a small of Veterinary Medicine, calculi. While the genetic defect that causes this disease splenic nodule. The dog was hospitalised and treated University of California-Davis, fl One Shields Avenue, Davis, CA in Dalmatians is well known among clinicians, this is the with intravenous uids (type unknown) and intraven- 95616,USA first clinical case documented in the Weimaraner breed. ous antimicrobials (ampicillin and enrofloxacin: 3Department of Population This dog shared the same SLC2A9 mutation as dosage unknown) and was discharged three days Health and Reproduction, Dalmatians, which likely predisposed this dog to later. School of Veterinary Medicine, University of California-Davis, developing urate calculi. For dogs where urate uroliths The dog was represented to the primary care veter- One Shields Avenue, Davis, CA are suspected on imaging studies, genetic testing may inarian five weeks later for lethargy and was found to 95616,USA be warranted to help elucidate any predisposing factors be febrile (40.0°C (104.0°F)). An aerobic urine for stone formation. Knowing the aetiology of the stone culture was positive growth of Escherichia coli. Correspondence to formation will alter the therapeutic approach for A focused abdominal ultrasound was performed by Dr Jodi L. Westropp, fi [email protected] treatment and management. the same veterinarian and identi ed thickening of the right ureter, continued right ureterolithiasis and a Received 19 September 2013 static splenic nodule. These findings were concerning Revised 19 December 2013 for bacterial ureteritis, pyelonephritis, or combin- Accepted 8 January 2014 BACKGROUND Urate-containing calculi have comprised approxi- ation of the two, and the dog was administered enro- mately 25 per cent of the calculi analysed at our floxacin (approximately 5 mg/kg (2.2 mg/lb), orally, laboratory each year from dogs (Low and others every 24 h) and discharged. 2010). Unlike most other breeds of dogs, Thirteen days later, the dog was re-presented to Dalmatian dogs have a well described alteration in his primary care veterinarian due to anxiety and purine metabolism that leads to the excretion of vomiting. Additionally, the dog was stranguric and uric acid in the urine rather than excretion of the not able to urinate the night prior to presentation, more soluble metabolite, allantoin (Keeler 1940, but voided with some difficulty the following Kuster and others 1972). All Dalmatians excrete morning just prior to examination at the primary relatively high amounts of uric acid (400–600 mg care veterinarian. Over the course of the day, the of uric acid per day as compared with 10–60 mg/ dog’s stranguria progressed and the primary care day in non-Dalmatian dogs); however, not all veterinarian diagnosed a urethral obstruction and Dalmatians form urate stones (Bartges and others admitted the dog to the hospital. A urinary catheter 1999). Bannasch and others (2008) identified a was inserted into the bladder and he was adminis- mutation in the SLC2A9 transporter as the cause of tered enrofloxacin again (approximately 5 mg/kg the change in uric acid handling by Dalmatians by (2.2 mg/lb), orally, every 24 h) as well as amoxicil- positional cloning using an interbreed backcross lin (23 mg/kg (10.4 mg/lb), orally, every 12 h), and (Safra and others 2005, 2006, Bannasch and others was referred to the VMTH the following morning. 2008). This genetic abnormality has been described Upon presentation to the VMTH, he was bright in other breeds (Karmi and others 2010). There is and alert, but anxious. His vital signs were within currently a commercial DNA test developed by the normal limits. His rectal temperature was normal at Veterinary Genetics Laboratory (http://www.vgl. this time at 37.9°C (100.3°F). No significant abnor- ucdavis.edu/services/Hyperuricosuria.php) to iden- malities were noted on physical examination. His tify the mutation in the SLC2A9 transporter. bladder was palpable, but not enlarged, and penis and prepucial area appeared normal. While in transit to the VMTH, the dog removed the urinary catheter. CASE PRESENTATION A six-year-old male castrated (26 kg (57.2 lbs)) To cite: Westropp JL, Weimaraner was referred to the William R Prichard INVESTIGATIONS Johnson EG, Fuller MC, et al. Vet Rec Case Rep Published Veterinary Medical Teaching Hospital (VMTH) at A complete blood count (CBC) was performed, online: [please include Day the University of California, Davis for possible renal, and all haematologic values were within normal Month Year] doi:10.1136/ ureteral and cystic calculi. Two months prior to refer- limits. Serum biochemical analyses are reported in vetreccr-2013-000016 ral, the dog was presented to the primary care Table 1. Only mild abnormalities were present, and Westropp JL, et al. Vet Rec Case Rep 2014;2:e000016. doi:10.1136/vetreccr-2013-000016 1 Downloaded from vetrecordcasereports.bmj.com on May 15, 2014 - Published by group.bmj.com Veterinary Record Case Reports right ureter was compatible with bilateral mineralised nephro- TABLE 1: Biochemical panel for this Weimaraner at initial liths with multiple right ureteroliths. Bilateral hydroureter presentation to the VMTH and 15 days postcystotomy without significant renal diverticular distention suggested bilat- Initial 15 Days after Reference eral chronic partial ureteral obstruction. Mineralised sediment presentation cystotomy range Units and debris within the lumen of the urinary bladder was compat- ible with small cystoliths. The splenic nodule may have repre- Anion gap 23 14 12–20 mol/l sented a benign or malignant change; biopsy was recommended. Sodium 147 146 143–151 mmol/l Preprandial and postprandial serum bile acids were submitted Potassium 4.3 4.3 3.6–4.8 mmol/l to rule out an underlying hepatopathy as a cause for suspected Chloride 110 113 108–116 mmol/l urate urolithiasis (see differentials). Both values were within the Bicarbonate 18 23 20–29 mmol/l laboratory’s reference range (preprandial 0 μMOL/l and post- Phosphorus 4.9 4.9 2.6–5.2 mg/dl prandial 6 μMOL/l; reference interval 0–12 μmol/l). A buccal Calcium 10.7 10.8 9.6–11.2 mg/dl mucosa swab DNA sample was submitted for testing at the BUN 12 19 11–33 mg/dl Veterinary Genetics Laboratory at UC Davisi, and results identi- Creatinine 1.0 0.7 0.8–1.5 mg/dl fied this dog as positive for two copies of the mutation that lead Glucose 84 83 86–118 mg/dl to hyperuricosuria and predisposes dogs to form upper or lower Total protein 6.0 5.3 5.4–6.9 g/dl urinary urate urolithiasis. Albumin 3.2 2.9 3.4–4.3 g/dl Globulin 2.8 2.4 1.7–3.1 g/dl ALT 29 30 21–72 IU/l DIFFERENTIAL DIAGNOSIS fi AST 40 31 20–49 IU/l On the basis of history and clinical and diagnostic imaging nd- Creatine kinase 284 158 55–257 IU/l ings done thus far, our primary differentials included pyelo- Alkaline 156 151 14–91 IU/l nephritis, ureteral calculi and urethroliths resulting in a phosphatase secondary partial or complete urethral obstruction. Differential GGT 3 3 0–5 IU/l diagnoses for urolith composition included calcium oxalate, Cholesterol 316 343 139–353 mg/dl urate, struvite and cystine; the latter was less likely due to the Bilirubin total 0.1 0.1 0.0–0.2 mg/dl urinalysis, and because Weimaraners have not been described as VMTH, Veterinary Medical Teaching Hospital a breed predisposed to cystine formation (Low and others 2010). While calcium oxalate and struvite are the most common uroliths submitted to stone analysis laboratories from dogs, these calculi are radiodense. Although struvite uroliths are all liver function parameters were within the reference ranges. usually less radiodense than calcium oxalate, they are visible on A urine sample was collected by cystocentesis and submitted for radiography and often associated with urease-producing bacteria fi urinalysis and urine culture. The urine speci c gravity was in dogs, such as Staphylococcus species (Osborne and others 1.018 and the urinary pH was 6.0; 25 mg/dl of protein was 1981). Although this dog had a bacterial UTI, most E coli – – present. There were 3 5 white blood cells/HPF and 50 100 red species do not have significant urease producing capabilities. blood cells/HPF. No bacteria or crystals were reported, and Due to the sonographic evidence of upper and lower urinary aerobic urine culture was negative for bacterial growth. The dog tract uroliths which lacked radiopacity, urate uroliths were con- fl was still receiving the enro oxacin and amoxicillin at the time sidered most likely. Primary differentials for the splenic nodule these analyses were performed.