Obstructive struvite ureterolithiasis in 4-month-old intact male Bernese mountain dog

Abstract

A 4-month-old, 7 kg, intact male, Bernese mountain dog was presented for obstructive struvite ureterolithiasis. Multiple urethroliths, ureteroliths, and urocystoliths were present. Based on an abdominal ultrasound, there was severe left hydronephrosis and hydroureter from distal ureterolith obstruction, just proximal to the vesicoureteral junction. The dog was not azotemic. Successful treatment was accomplished via ventral cystotomy. Bladder wall culture revealed a methicillin-resistant Staphylococcus spp. No predisposing cause was identified. There are no known genetic predispositions in Bernese mountain dogs for struvite urolithiasis. The urinary tract infection resolved with surgical retrieval of the uroliths and antibiotic treatment. The dog remained clinically normal after the cystotomy but developed a subclinical urinary tract infection 4 mo post-operatively.

Key clinical message:

Urolithiasis is rare in pediatric veterinary patients. To the authors’ knowledge, this is the first report of obstructive ureterolithiasis in a puppy. There is no known genetic predisposition for urolithiasis in Bernese mountain dogs.

Introduction

Urolithiasis is a common diagnosis in dogs with lower urinary tract disease. The most common uroliths that form are struvite (magnesium ammonium phosphate hexahydrate) and calcium oxalate (1–4). Struvite urolithiasis occurs from a combination of factors including diet, alkaline urine, presence of urinary tract infection (UTI) by urease-producing pathogens, and breed predispositions (1–3). Struvite urolithiasis is typically diagnosed in middle-aged dogs (2,4). It is rare for such uroliths to develop in immature patients (4–6). When struvite urolithiasis is detected in immature dogs, infection-induced causes are most common (6). To the authors’ knowledge, struvite ureterolithiasis has not yet been reported in pediatric veterinary patients. In human nephrology, pediatric uroliths occur in only 0.06 to 1% of patients presenting to North American hospitals and are typically due to dietary imbalances (7,8).

This report describes the first known case of obstructive struvite ureterolithiasis in a young dog with no anatomic predisposition for urinary tract infection. The case was successfully managed in the short term with surgical removal of uroliths via ventral cystotomy.

Case description

A 4-month-old, 7 kg, intact male, Bernese mountain dog presented with acute stranguria of 24 h duration. The primary care veterinarian palpated a large, non-expressible bladder. Abdominal radiographs identified multiple uroliths. No treatments were initiated as the dog was immediately transferred to a referral veterinary clinic. There were no previous urinary signs, and he was formerly clinically normal. Prior to presentation, he was fed a commercial puppy food (Natural Balance puppy formula) with raw diet supplementation (30 to 50% of the diet, based on the owner’s estimate).

On presentation to the referral center, the dog was bright with normal vital parameters. The urinary bladder was large, turgid, non-expressible, and painful on palpation. Radiographs were repeated to acquire standard views of the caudal abdomen and perineum. In addition to multiple cystoliths, 1 urethrolith was observed in the distal urethra at the os penis (Figure 1). Retrograde urohydropropulsion was performed and an indwelling urinary catheter was placed. A complete blood (cell) count (CBC) revealed a mild normochromic normocytic regenerative anemia [hematocrit 31%; reference range (RR): 36 to 60%] with reticulocytosis (reticulocytes 2.0%; RR: 0 to 1%; absolute reticulocytes 90 × 10⁹/L; RR: < 60 × 10⁹/L) and nucleated red blood cells (1/100 RBC; RR: 0 to 1/100 RBC). The mild anemia was attributed to hematuria and potentially due to the young age of the patient. Serum biochemistry revealed the absence of an azotemia [blood urea nitrogen (BUN) 7.0 mmol/L; RR: 2.1 to 11.1 mmol/L; creatinine 29 μmol/L; RR: 44 to 141 μmol/L]. Total protein (52 g/L; RR: 50 to 74 g/L), including albumin (33 g/L; RR: 27 to 44 g/L), cholesterol (4.85 mmol/L; 2.38 to 10.0 mmol/L), and liver enzymes (ALT 18 U/L; RR: 12 to 118 U/L; ALP 115 U/L; RR: 5 to 131 U/L) were all within reference ranges. Phosphorus was moderately elevated; 2.82 mmol/L (RR: 0.81 to 1.94 mmol/L). The chemistry results were consistent with the patient’s young signalment. Urinalysis identified a urine specific gravity (USG) of 1.029, a basic pH of 8.0, 2+ proteinuria, pyuria (11 to 20 cells/HPF), hematuria (11 to 20 cells/ HPF), struvite crystalluria (11 to 20/HPF), bacteriuria (51 to 100 cocci/HPF), and squamous epithelial cells (2 to 3/HPF).

Figure 1.

A, B, C — Abdominal radiographs. A single 4.5-mm urethrolith (black arrow) is observed at the distal urethra. Two ureteroliths [rectangular mineral structure (white arrowhead), and triangular mineral structure (white arrow)] are observed dorsal to the caudal aspect of the urinary bladder on both lateral views. The uroliths are difficult to observe on the ventrodorsal view due to decreased detail from abdominal effusion and young patient age. A — Right lateral view. B — Left lateral view. C — Ventrodorsal view.

An abdominal ultrasound examination identified marked left hydronephrosis and hydroureter with a left ureteral obstruction (Figure 2). Marked renal pelvic distension was present measuring up to 25 mm in diameter and 41 mm in length (Figure 2 A). The proximal left ureter was markedly fluid distended, measuring up to 20 mm. Two large obstructing shadowing ureteroliths of cuboidal shape (6 and 8 mm, respectively) were lodged adjacent to each other in the left vesicoureteral junction (Figure 2 B). The right kidney was normal, and the right ureter was mildly thickened. In the urinary bladder, there were shadowing cystoliths up to 7 mm in diameter (Figure 2 C). Many more uroliths were visible than were evident on the abdominal radiographs. Moderate peritoneal effusion was observed and was suspected to be a result of lower urinary tract obstruction. This was aspirated and submitted for culture. Ultimately, Staphylococcus pseudointermedius, sensitive to amoxicillin/clavulanic acid, was isolated. The remainder of the abdomen, including the liver and the portal vasculature was unremarkable.

Figure 2.

A, B, C — Abdominal ultrasound images. A — Marked left hydronephrosis. B — Two large shadowing obstructive ureteroliths lodged adjacent to each other in the left vesicoureteral junction measuring 6 mm (left; arrowhead) and 8 mm (right; arrow). C — Urinary bladder with multiple cystoliths in a thick layer of sediment.

The dog was treated with oral amoxcillin/clavulanic acid (Clavaseptin; Vétoquinol, Lavaltrie, Quebec), 18 mg/kg body weight (BW), PO, q12h, for the UTI and suspected ascending ureteritis. Methadone (methadone hydrochloride, 10 mg/mL; Dechra, Pointe-Clarie, Quebec), 0.1 mg/kg BW, IV, q6h was initiated for pain control. The dog was also placed on crystalloid intravenous fluids (Plasma-lyte A; Baxter, Mississauga, Ontario,) 35 mL/h.

Secondary diagnostic tests that were performed after the initial investigation included pre- and postprandial bile acid measurements to rule out a hepatic vascular anomaly as a predisposing factor to urolith formation. These results were within the reference range (preprandial 1.5 μmol/L; RR: < 13 μmol/L; postprandial 4.9 μmol/L; RR: < 25 μmol/L). A follow-up biochemistry panel performed 3 d after initial presentation indicated a persistent lack of azotemia (BUN 3.8 mmol/L; RR: 2.5 to 8.9 mmol/L; creatinine 35 μmol/L; RR: 27 to 124 μmol/L).

Surgery for stone retrieval and renal decompression was advised. The dog was stable and hospitalized over the weekend while awaiting diagnostic test results and surgical intervention. In surgery, a routine ventral cystotomy was performed. There were no ectopic ureters, ureteroceles, or urachal anomalies identified. The previously noted free abdominal fluid was not appreciated. The left ureter was massively dilated and obstructed by 2 large ureteroliths. Following ventral cystotomy, the left ureteral orifice was incised cranially along the ureteral papilla (sphincterotomy), which allowed for a mosquito hemostat to be introduced into the ureter to grasp the larger ureterolith for normograde removal. The smaller ureterolith then passed without intervention. Multiple urocystoliths and urethroliths of varying sizes (1 to 7 mm) were removed from the urinary bladder via the cystotomy incision. The left ureteral mucosa was sutured to the bladder mucosa with 5-0 polydioxanone (PDS-II Suture; Ethicon, Somerville, New Jersey, USA) in a simple interrupted pattern within the lumen of the urinary bladder. The cystotomy incision was closed with 4-0 polydioxanone (PDS-II Suture; Ethicon) in a simple continuous pattern. The abdomen was closed routinely. The stones were submitted to the University of Guelph, Canadian Veterinary Urolith Centre for analysis. A culturette of the urine, uroliths and bladder mucosa was submitted for aerobic and anaerobic bacterial cultures.

Post-operatively, a positive contrast cystourethrogram was performed with nonionic iodinated contrast (Iohexol; Omnipaque, Marlborough, Massachusetts, USA) to confirm complete urolith removal. A positive contrast study was chosen as many of the uroliths were not radio-opaque prior to surgery. This study did not identify any residual uroliths. The dog recovered very well from surgery and was discharged the following day. At the time of discharge, his renal values remained normal (BUN: 5.2 mmol/L; RR: 2.5 to 8.9 mmol/L; creatinine: 39 μmol/L; RR: 27 to 124 μmol/L), and he was urinating normally.

Culture of the bladder mucosa and uroliths demonstrated a methicillin-resistant coagulase negative Staphylococcus spp. (MRSP) that was resistant to amoxicillin, cephalosporins (cefadroxil, cefazolin, cefovecin, cefpodoxime, and cephalexin), and to the antibiotic in use, amoxicillin/clavulanic acid. However, this MRSP was susceptible to clindamycin and enrofloxacin. Antibiotic therapy was adjusted to clindamycin (Clinacin; Intervet Canada, Kirkland, Quebec), 75 mg, PO, q12h. Given the dog’s age, a commercial diet formulated for growth in a large-breed dog with added water was recommended, as there are currently no prescription diets designed for dissolving struvites that are formulated for growth. The owner elected to continue feeding Natural Balance puppy formula with added water. The raw diet was discontinued.

At the 2-week follow-up examination, a focal ultrasound of the urinary tract system was performed. Marked and worsened left-sided pyelectasia (renal pelvis measuring 128 mm) with left ureteral dilation (53 mm) persisted. There was no ureterolith or stricture observed (urine jets identified). Debris was present within the urinary bladder. Urine culture performed at this time was negative for bacterial growth. Clindamycin was continued for a total treatment duration of 3 wk. At 4 mo after surgery, the patient was clinically normal. On a repeat urinalysis, struvite crystalluria and a urinary tract infection were diagnosed. Escherichia coli and Enterococcus spp. were identified on bacterial culture and were sensitive to all antibiotics, suggesting reinfection and not relapse. A follow-up abdominal ultrasound identified that there was an approximately 50% decrease in the size of the left renal pelvis (83 versus 128 mm) and proximal ureteral dilation (24 versus 53 mm), indicating progressive improvement. Treatment with amoxicillin (Amoxicillin; Vétoquinol), 500 mg, PO, q8h for 2 wk allowed for resolution of this infection. Two months following that recheck, the patient continued to be clinically normal without subclinical bacteriuria. Mineral analysis from the Canadian Veterinary Urolith

Centre revealed that the uroliths were composed of magnesium ammonium phosphate hexahydrate (struvite). The stones of the uroliths were 95% struvite, and 5% calcium phosphate. The shell of the uroliths were 100% struvite.

Discussion

Struvite urolithiasis is one of the most common types of uroliths in canine patients (1–4). Sterile struvite urolithiasis in dogs is rare (1,9,10). Almost all cases of struvite urolithiasis arise from a UTI by urease-producing bacteria, such as Staphylococcus spp. or Proteus spp. (1). In our case, the dog suffered from a concurrent MRSP infection. No underlying anatomical cause for this UTI was identified. Contribution of diet to stone formation was possible in this case since a combination of raw food with commercial kibble was fed prior to surgery. Perhaps the raw diet had an unbalanced calcium-to-phosphorus ratio and/or high magnesium content, leading to increased likelihood for forming struvite uroliths (1,11). Urolithiasis is a predisposing factor to urinary tract infections (12) and may partially explain the presence of a urinary tract infection in a male dog. Anatomical differences between male and female dogs also affect the predisposition to urinary tract infections. The distance between the urethra and the anus is greater in male dogs, making urinary tract infections less likely in the male patient (12). In adult male patients, the role of the prostate gland in the pathogenesis of urinary tract infections cannot be ignored. Indeed, the presence of prostatitis will classify a UTI as complicated and will subsequently affect how the infection is treated (12,13). In the pediatric prostate, there are few, if any prostatic tubules open to the urethra (14,15). Thus, the role of the prostate in pediatric male UTIs is unclear. The authors suspect the prostate does not typically serve as nidus of infection in a pediatric veterinary patient, although there are insufficient data to substantiate this clinical suspicion. There are infrequent reports of human neonatal prostatic abscesses in the literature, suggesting that it is at least possible for the prepubescent prostate to support infection (16,17). In our case, the prostate was ultrasonographically normal. We believe it is unlikely to have had a substantial role in this dog’s lower UTI.

Breed predisposition for struvite urolithiasis has not been well-investigated (3). Okafor et al (1) reported that struvite urolithiasis occurred more commonly in toy breed and small breed dogs (1). In contrast, in a more recent study by the Canadian Veterinary Urolith Centre, struvite urolithiasis was over-represented by medium- to large-breed dogs (3). Bernese mountain dogs were the source of only 0.15% of all uroliths submitted; however, over half of the uroliths submitted from this group were struvites (3). This was not unexpected, however, given that struvite urolithiasis is one of the most common uroliths recovered and this does not specifically indicate that there is a breed predisposition to stone formation.

The mean age at diagnosis for struvite urolithiasis ranges from 4.25 to 5.92 y (2). For all age groups, females are more commonly affected than males, which is consistent with the infection-induced nature of struvite uroliths (1,3). It is rare to detect uroliths in immature dogs (4–6). Between 1981 and 2002, 1.2% of uroliths analyzed at the Minnesota Urolith Center came from dogs less than 12 mo of age (6). The most common type of stone obtained from these immature dogs was struvite, and the most common cause was infection-induced (6). Our case of an immature male dog was consistent with infection-induced struvite urolithiasis. It is, however, a unique presentation, as the first reported case of ureterolithiasis in such a signalment.

Few reports exist on urolithiasis in pediatric small animal patients (9,18–24). Pediatric struvite urolithiasis in both dogs and cats were most often associated with an anatomic predisposition to the development of UTIs such as urachal diverticula (19,24,25) or a patent urachus (5,25). As discussed previously, most cases have typically been associated to a UTI with staphylococci (18–21). Struvite urolithiasis in pediatric dogs with no known anatomic predisposition have been described (9,18,20–23). Various treatments have been reported for these cases, which include surgery for stone retrieval (20,21), surgical correction of predisposing factors including urachal diverticula, patent urachus, and urachal cysts (5,25), as well as medical dissolution (9,19). These approaches have all apparently been successful in the short term, but a lack of long-term follow-up information and a deficiency of prospective trials makes it impossible to predict the clinical course of urolithiasis in this patient population.

Removal of the uroliths and ureteroliths required surgical intervention. Possible approaches to achieve this goal included ventral cystotomy with removal of the uroliths via the ureterovesicular orifice or ureteral reimplantation. Ureteral stenting and subcutaneous ureteral bypass were not strongly considered due to this patient’s age, and significant growth potential. Stones in the urinary bladder would also not be directly addressed with a ureteral stent. The stones would have required medical dissolution. Given the recent urethral obstruction and documented urinary tract infection, a minimally invasive approach along with medical dissolution of an unknown stone type would not have been ideal since, as already discussed, there is no approved diet for stone dissolution in patients of this age. In addition, immediate removal of the stones was considered important to quickly eliminate the nidus of infection, given concern for potential resistant bacteria and a septic process. Without immediate removal, long-term antibiotics would also have been required. Nephrectomy was also not strongly considered to preserve renal function in this young dog. Minimally invasive procedures such as percutaneous cystolithotomy (PCCL), and laser lithotriopsy (11) were considered to be less ideal for this case. Percutaneous cystolithotomy would have been able to access the uroliths but not the ureteroliths. In addition, the attending surgeon did not find that the benefits of PCCL were warranted in cases with multiple stones due to the large increase in procedure time, perceived increased risk of intraoperative complications, and need for conversion to an open approach and its associated costs. As stated in Cruciani et al (26), multiple uroliths are challenging to remove with PCCL and the risk of prolonged anesthesia must be weighed over the potential benefits of a minimally invasive approach. Laser lithotripsy potentially could have been employed, although with the large stone burden, excessively long procedural times would also have been of concern. Furthermore, the entire urinary tract, including the kidneys and ureters bilaterally could not have been explored with either minimally invasive approach, nor could the source of peritoneal effusion be confirmed, making an open approach preferred in this dog.

The International Society for Companion Animal Infectious Disease (ISCAID) has provided many guidelines to direct antimicrobial therapy in small animal patients with urinary tract infections (27). Antibiotic selection in our patient did not follow all of their recommendations for various reasons, largely due to the complicated nature of his case. The use of amoxicillin with clavulanic acid as an initial antimicrobial lacks evidence; however, this medication was initiated prior to transfer to the attending surgeon. As the antimicrobial was in use for 3 d, a mid-treatment change of drug was not performed until culture and sensitivity results were available after surgery. As previously discussed, the culture results that were available from the urolith and bladder mucosa identified an MRSP sensitive to clindamycin and enrofloxacin only. Although clindamycin is not included in the ISCAID guidelines, enrofloxacin was not chosen due to the concerns over potential arthropathies in juvenile canine patients (28). Indeed, Plumb’s Veterinary Drugs suggests avoidance of enrofloxacin in large to giant breed dogs until more than 12 to 18 mo of age (29). The length of treatment was extended beyond what ISCAD guidelines suggest due to the previously documented peritoneal infection, in addition to the complicated urinary tract infection.

At the 4-month recheck, subclinical bacteriuria was documented through bacterial culture with continued hydronephrosis and ureteral dilation. The ISCAID guidelines would generally not have recommended treatment with antibiotics in this scenario. The attending internist elected to treat with amoxicillin, due to the risk of development of pyelonephritis in this patient, as the kidney and ureter remained grossly abnormal on abdominal ultrasound. The authors acknowledge that in retrospect, treatment likely could have been accomplished with a shorter duration of antibiotic therapy (3 to 5 d), as per ISCAID guidelines.

As noted in the case summary, a mild anemia was detected on this dog’s CBC before surgery. The hematocrit was 31%, below the low end of the reference range for adult patients at 36%. Reticulocytosis and nucleated red blood cells were noted on blood smear evaluation, suggesting the anemia was regenerative. Anemia in this case was attributed to hematuria, which was documented on the urinalysis and grossly visible in the urinary catheter closed collection system during hospitalization. In addition to the hematuria, it is well-accepted that the hematocrit of young patients is lower than that of the adult (30). The authors are unaware of any studies investigating the normal hematocrit of Bernese mountain dogs at various ages (30), and so the relative contribution of hematuria and age is difficult to quantify. Follow-up packed cell volume (PCV) and total solids (TS) during this dog’s hospitalization did not indicate a substantial decline in the hematocrit.

In summary, our case apparently represents the first report of an obstructive ureterolith in a young veterinary patient. There is no clear breed predisposition to struvite urolithiasis in Bernese mountain dogs and no anatomic predisposition was identified in our patient. Surgical stone retrieval and medical management were successful at short-term follow-up for treatment of this patient. However, at 4 mo post-operatively, reinfection with another UTI occurred despite progressive improvement in the initial renal and ureteral changes. This dog will continue to have careful monitoring for UTIs with further diagnostic testing as required. At 1 y after surgery, this dog has not had any stone recurrence or UTI. The raw diet has been discontinued, and thus will no longer be a contributing factor.