Intravesical Ureterocele With Concurrent Renal Dysfunction in a Dog: A Case Report and Proposed Classification System

Introduction

A ureterocele is a cystic dilatation of the submucosal portion of the distal ureter¹ entirely within the bladder (intravesical) or in an abnormal position in association with an ectopic ureter (ectopic).² It has been commonly reported in humans, but to the authors’ knowledge, there have been only 10 reports of ureteroceles in dogs published in the veterinary literature.^3–12 Five dogs had intravesical ureteroceles; four were unilateral,⁴⁸¹¹ of which one was secondary to neoureterocystostomy⁷ and one was bilateral.¹⁰ Five dogs had ectopic ureteroceles, of which two were bilateral³⁵ and three were unilateral.⁶⁹¹² None of these dogs had concomitant renal dysfunction.

This report describes successful surgical resection of a right unilateral, intravesical ureterocele with subsequent reduction of ipsilateral hydroureter in a 5-year-old female Pekingese that also had bilateral renal dysfunction and suffered progressive, mild azotemia postoperatively. The authors also propose a classification system for canine ureteroceles, modified from the human literature, that may be helpful in encouraging thorough urinary tract evaluation and predicting outcome.

Case Report

A 5-year-old, 4.0-kg, female Pekingese was referred to the University of Georgia Veterinary Teaching Hospital (UGA-VTH) with a 3-week history of intermittent vomiting and “dragging her rear end” and a 2-week history of decreased appetite. The owners purchased the dog at a young age and had noticed no previous abnormalities. The referring veterinarian examined the dog and submitted a complete blood count (CBC) and serum biochemistry panel 3 days before the dog was referred. Pertinent results of the blood work included a hematocrit (Hct) of 39% (reference range, 36% to 60%); neutrophilic leukocytosis (16.2 × 10³ white blood cells [WBC]/μL; reference range, 4.0 to 15.5 × 10³ WBC/μL; 11.35 × 10³ neutrophils/μL; reference range, 2.06 to 10.69 × 10³ neutrophils/μL) with monocytosis (2,754 monocytes/μL; reference range, 0 to 840 monocytes/μL); normal blood urea nitrogen (BUN, 15 mg/dL; reference range, 6 to 25 mg/dL), creatinine (1.3 mg/dL; reference range, 0.5 to 1.6 mg/dL), and phosphorus (4.3 mg/dL; reference range, 2.5 to 6.0 mg/dL); increased serum activities of alkaline phosphatase (ALP, 6,035 U/L; reference range, 5 to 131 U/L) and alanine aminotransferase (ALT, 2,165 U/L; reference range, 12 to 118 U/L); hyperbilirubinemia (4.2 mg/dL; reference range, 0.1 to 0.3 mg/dL); and hypercholesterolemia (461 mg/dL; reference range, 92 to 324 mg/dL). The day before referral, preprandial bile acids were increased (118.4 μmol/L; reference range, 0.0 to 5.0 μmol/L).

Initial physical examination at UGA-VTH revealed poorly localized abdominal pain. Pollakiuria was noted during careful observation of urinary habits. Multiple episodes of squatting with only small amounts of urine being voided were seen. This behavior could have been interpreted by a pet owner as the dog “dragging her rear end.” In addition, palpation of the urinary bladder after urination elicited a pain response and revealed continued urinary bladder distention. Abnormalities of a CBC and serum biochemistry profile included mild microcytic (61.6 fl; reference range, 66 to 77 fl), normochromic anemia (Hct, 33.2%; reference range, 35% to 57%); mild leukocytosis (14.5 × 10³ WBC/μL; reference range, 5.1 to 13.0 × 10³ WBC/μL) with lymphocytosis (4,060/μL; reference range, 400 to 2,900/μL); normal BUN (24 mg/dL; reference range, 10 to 30 mg/dL), creatinine (1.4 mg/dL; reference range, 0.5 to 1.5 mg/dL), and phosphorus (3.4 mg/dL; reference range, 3.0 to 5.2 mg/dL); decreasing serum activities of ALP (4,850 U/L; reference range, 13 to 122 U/L) and ALT (975 U/L; reference range, 12 to 108 U/L); decreasing hyperbilirubinemia (0.7 μg/dL; reference range, 0.0 to 0.2 μg/dL); and slightly decreased blood bicarbonate (12 mmol/L; reference range, 14 to 24 mmol/L). Urine was collected by cystocentesis for urinalysis and culture. Urinalysis was within reference ranges except for hyposthenuria (urine specific gravity [USG], 1.006) and bilirubinuria (2+). Aerobic urine culture resulted in no bacterial growth. Survey thoracic radiographs were done as part of a preanesthetic workup and to rule out pulmonary metastatic neoplasia, since hepatic neoplasia was on the initial rule-out list. Survey abdominal radiographs were done to evaluate the liver. Radiographic findings included mild right-heart enlargement and microhepatia. The left kidney was not clearly visible.

The dog was given nothing by mouth because of her intermittent vomiting. She was treated with intravenous (IV) 0.45% sodium chloride with 2.5% dextrose given at 1.25× maintenance rate for the first 36 hours of hospitalization. No vomiting occurred during 48 hours of fasting, after which she was fed a canned canine prescription diet^a for liver disease.

On the third day of hospitalization, additional diagnostic tests were done to assess the small liver and urinary tract. An ammonia tolerance test was done to assess liver function, and a coagulation profile was done in anticipation of a percutaneous liver biopsy using ultrasound guidance. Results of both tests were within reference ranges. An abdominal ultrasound examination was also performed. The liver was difficult to image because of its small size, so a percutaneous biopsy was not attempted. Both kidneys were hyperechoic and had distorted cortical margins. A small, thin-walled, round structure containing anechoic fluid was noted within the neck of the urinary bladder [Figure 1]. This structure appeared to communicate with the right ureter, which was dilated to a 0.5-cm diameter distally. Ultrasonographic findings of the urinary tract were consistent with right hydroureter and intravesical ureterocele. An IV urogram (IVU) was done to further evaluate the urinary tract using sodium iothalamate^b (0.45 mL/kg body weight) administered as a rapid IV bolus. The left kidney was small. Both renal pelves were dilated, and the pelvic recesses were poorly filled with contrast medium. The opacification of the renal parenchyma was similar in both kidneys, but the left ureter was poorly opacified. Radiographs taken 5 minutes after injection of contrast showed a dilated, tortuous right ureter that appeared to be confluent with a spherical structure within the neck of the urinary bladder. The intravesical spherical structure filled with contrast before the remainder of the bladder. Radiographs taken 40 minutes after injection of contrast showed both ureterocele and the bladder filled with contrast [Figure 2].

By the fourth day of hospitalization, the dog’s appetite and attitude had improved significantly. Results of a serum biochemistry profile included normal BUN (11 mg/dL), creatinine (1.3 mg/dL), and phosphorus (3.5 mg/dL); decreasing serum activities of ALP (2,871 U/L) and ALT (506 U/L); and normal bicarbonate (17 mmol/L). Surgery was planned for the next day.

An exploratory celiotomy was done on the fifth day of hospitalization to biopsy the liver and left kidney and to resect the ureterocele. The liver did not appear as small as expected based on the abdominal radiographs and ultrasound. The left kidney was approximately two-thirds the size of the right kidney, which was grossly normal. About 50% of the surface of the left kidney looked indented. The right ureter was grossly dilated as it approached the bladder. The left ureter was identified external to the bladder and appeared normal in size. A biopsy of the liver was done by placing a ligature of 3-0 polydioxanone around the margin of a liver lobe and removing a small piece of liver distal to the ligature. A 2-mm wide, corticomedullary wedge biopsy of the left kidney was collected using a no. 15 scalpel blade, and the renal capsule was closed with horizontal mattress sutures of 3-0 polydioxanone. Biopsy samples were not taken from the right kidney, because findings of the IVU suggested that the majority of urine production was occurring in the right kidney; therefore, additional iatrogenic damage to the right kidney was not warranted. The bladder was incised along its ventral midline and drained. The ureterocele was intact, distended, and taut in the caudal urinary bladder [Figure 3]. A communication between the ureterocele and the bladder could not be seen grossly at surgery. The ureterocele was incised, and a portion of its wall was submitted for histopathological evaluation. A 3.5-French, red rubber catheter was passed easily through the incised ureterocele and into the right ureter in retrograde fashion toward the right kidney. The ureteral orifice was located more medially than normal. Urine flowed freely through the right ureteral orifice in a normal peristaltic manner throughout the procedure. The opening of the left ureter could not be found within the ureterocele or in the trigone of the urinary bladder. The authors suspect that either the urine flow from the left kidney was negligible (as suggested by the IVU), the left vesicoureteral opening was stenotic, or that the left ureter may have been ectopic. There was no other evidence to suggest ectopia (e.g., incontinence), so minimal urine flow from the left kidney or stenosis of the vesi-coureteral opening seemed more likely. The ureterocele was resected to the level of the bladder wall. The edges of the ureterocele wall were left unsutured. A single, right vesi-coureteral opening was visible after resection of the ureterocele. The bladder was flushed with sterile saline, biopsied at the edge of the bladder incision, and closed in a single, inverting layer. The abdomen was flushed with warm, sterile saline and was closed routinely.

Microscopically, the left kidney had chronic, lymphocytic, plasmacytic, tubulointerstitial nephritis characterized by irregular areas of cortical fibrosis containing atrophied tubules, sclerotic glomeruli with dilated Bowman’s capsules, and a mild lymphoplasmacytic infiltration [Figure 4]. Microscopically the urinary bladder was normal. The ureterocele was lined by cuboidal to transitional epithelial cells that covered a layer of connective tissue, containing congested vessels and a few bundles of smooth muscle. In the liver, multiple binucleated hepatocytes, consistent with hepatocellular regeneration, were present.

Voided urine appeared bloody during the 24 hours immediately postoperatively, but neither stranguria nor dysuria was observed. Eighteen hours postoperatively, a CBC and serum biochemistry profile revealed moderate microcytic (62.2 fl), normochromic, regenerative (184.0 × 10³ reticulocytes/μL; reference range, 0 to 80.0 × 10³ reticulocytes/μL) anemia (Hct, 24.2%); leukocytosis (36.6 × 10³ WBC/μL) with mature neutrophilia (33.7 × 10³ neutrophils/μL; reference range, 2.9 to 12.0 × 10³ neutrophils/μL); mild hypoalbuminemia (2.6 g/dL; reference range, 2.7 to 4.4 g/dL); normal BUN (11 mg/dL), creatinine (1.3 mg/dL), and phosphorus (4.0 mg/dL); and a slightly decreased bicarbonate (12 mmol/L). The serum activities of ALP (1,630 U/L) and ALT (326 U/L) were continuing to decrease. The dog recovered rapidly after surgery and continued to eat well without vomiting. The dog was fed as before, until confirmation of resolution of liver disease.

The dog was reevaluated 6 weeks postoperatively. On physical examination, she was alert, energetic, and non-painful on abdominal palpation. She had not vomited since 4 days prior to surgery, and pollakiuria was not evident while observing her urinary habits. The authors’ assessment of the history of vomiting was that it was likely related to the liver disease, because the vomiting stopped as the liver enzymes began decreasing. A serum biochemistry panel and urinalysis showed normal serum activities of ALP (36 U/L) and ALT (45 U/L), mildly increased BUN (33 mg/dL) and creatinine (1.8 mg/dL), and a USG of 1.017 with no other abnormalities on urinalysis. Serum albumin (3.7 g/dL) and blood bicarbonate (21 mmol/L) concentrations had returned to normal. Intravenous urogram showed a decrease in the size of the right ureteral lumen and no ureterocele [Figure 5]. The decreased size of the right ureter could be explained by removal of partial outflow obstruction by the previous surgery or decreased volume of urine distending the ureter (e.g., lack of IV fluid therapy at this visit). The volume and rate of administration of contrast material were identical to the previous IVU. Dilated renal pelves were still present. There was no bacterial growth on urine culture. The diet was changed to a prescription canned food^c for management of renal failure.

Seven months after surgical correction of the ureterocele, blood and urine samples from the dog were mailed to the authors by the referring veterinarian. To the owners, the dog appeared normal in her behavior and appetite. There was persistence of renal failure since the 6-week postoperative examination, with a BUN of 49 mg/dL, creatinine of 2.0 mg/dL, and USG of 1.014. All other findings on urinalysis and urine culture were normal or negative, respectively. Serum phosphorus (5.2 mg/dL) was high normal, but the Hct (44.9%) and total leukocyte count (8.2 × 10³ WBC/μL) had normalized. Alkaline phosphatase (18 U/L), ALT (53 U/L), and total bilirubin (0.1 mg/dL) were normal. Other abnormalities were not detected. Causes for the previously radiographically diagnosed right-heart enlargement and microhepatia were not pursued or identified. Continued feeding of a prescription canned food for renal failure or a comparable low-protein diet, in addition to frequent monitoring of renal parameters with the necessary subsequent treatment, were recommended for management of chronic renal failure.

Discussion

Canine intravesical ureteroceles are often asymptomatic. Subsequently, they are infrequently diagnosed unless they are large and cause obstruction.⁸¹²¹³ Clinical signs associated with ureteroceles in dogs may include stranguria, pollakiuria, incontinence, and abdominal pain.^3–12 In the case reported here, the ureterocele was grossly large and taut and was causing partial obstruction of the proximal urethra, likely resulting in pollakiuria and abdominal pain. The ureterocele in this dog, however, was found incidentally. Vomiting was the reason for her presentation to the referring veterinarian, and referral of the dog was primarily for unresolved vomiting and suspected liver disease.

Complications associated with ureteroceles may include obstruction of the urethra, obstruction of the ipsilateral or contralateral ureters, or upper urinary tract infection. Obstructive nephropathy is characterized by an increase in urinary hydrostatic pressure with subsequent dilatation of the ureter, renal pelvis, renal parenchyma, and glomeruli.¹⁴ Hydroureter may predispose to vesicoureteral reflux and ascending upper urinary tract infections.¹⁵ Subsequently, permanent renal damage may occur. In the case of this report, there was moderate hydroureter, dilatation of the ipsilateral renal pelvis, and marked atrophy and fibrosis of the contralateral kidney. This is unique to the veterinary literature, because canine ureteroceles have not been previously reported in dogs with concurrent bilateral renal dysfunction. It is possible that the left renal fibrosis and poor contrast enhancement of the left ureter during IVU were a result of a congenital defect; renal disease unassociated with the ureterocele; obstruction of the left vesi-coureteral opening by the ureterocele, with resultant nephropathy and decreased urine production; previous upper urinary tract infection involving the left kidney; or some other unidentified cause.

There are two findings in this case report that deserve detailed explanations. The progression and resolution of anemia and the persistence and progression of azotemia in the dog of this report are interesting. This dog had microcytic anemia preoperatively that worsened after surgery. The anemia, however, was regenerative <24 hours postoperatively. Therefore, renal biopsy-associated hemorrhage cannot fully explain the anemia, since regeneration after surgical hemorrhage should not start for 48 to 72 hours postoperatively. Other factors that could have temporarily contributed to anemia include hemodilution from IV fluid therapy and repeated venipuncture for blood samples. Regenerative anemia can be explained by mechanisms of loss or lysis. A mild hemolytic process associated with the unexplained liver disease could have been masked by hepatic-origin hyperbilirubinemia. Alternatively, unnoticed blood loss could have occurred in the gastrointestinal tract, as urinary loss was ruled out by urinalysis on admission to the UGA-VTH. Regeneration appeared to occur as the clinical signs of liver disease (e.g., vomiting, inappetence) resolved.

The dog of this report also developed progressive, mild azotemia that was first documented 6 weeks postoperatively. An IVU done at that time ruled out the possibility of postrenal obstruction associated with resection of the ureterocele. In addition, the dog was not dehydrated at the 6-week recheck, ruling out prerenal causes of azotemia. The authors’ conclusion was that bilateral renal disease was the most likely cause of azotemia. Azotemia was not present preoperatively. It is possible that iatrogenic renal damage subsequent to the wedge biopsy of the left kidney contributed to the development of azotemia, but this cannot be the sole explanation, since renal azotemia requires bilateral disease. The right kidney may have been permanently damaged by the hydronephrosis associated with the ureterocele or may have been affected by the same chronic, lymphocytic, plasmacytic, tubulointerstitial nephritis that was documented in the left kidney. There is no way to prove the exact etiology, because a biopsy was not taken from the right kidney; but chronic nephritis is often bilateral. Progression of chronic nephritis was likely to occur whether or not surgical intervention occurred. It is also possible that the anesthetic episode may have contributed to progression of renal disease. Regardless of the etiology, it is evident that both kidneys in the dog of this report are dysfunctional, since azotemia requires the loss of at least 75% of the functional renal mass.

While surgery is often indicated for ectopic ureteroceles to alleviate the associated clinical signs of incontinence due to ectopic ureters, cystoscopic incision is commonly being used as the initial treatment for intravesical ureteroceles in humans.¹⁶¹⁷ This technique has decreased the need for surgical intervention.¹⁶¹⁷ Cystoscopic incision was not used in this case because of the dog’s small size and the indication for a surgical liver biopsy. In a larger dog with an intravesical ureterocele, cystoscopic incision could be considered.

The classification of ureteroceles has remained confusing in human^2161819 and veterinary medicine.⁸¹⁰ The American Academy of Pediatrics’ section on urology classifies human ureteroceles as intravesical and ectopic.² An intravesical ureterocele is a cystic dilatation of the distal ureter entirely within the bladder, whereas if any portion of the ureter or ureterocele is within the urethra, it is termed ectopic.² Methods of classification of ureteroceles in the veterinary literature have focused on morphological and anatomical location.⁸¹⁰ Previous veterinary reports have used the term “orthotopic” to describe intravesical ureteroceles.^47810–1221

The case presented in this report shows the inability of the anatomical classification system alone to describe abnormalities that may be seen concurrently with ureteroceles. There is no distinction between the extent of concomitant renal disease in dogs with ureteroceles. A functional classification system could offer a prognosis for future cases. Churchill, et al. proposed a grading system for human ectopic ureteroceles based on the renal unit at risk of being damaged.¹⁹ In humans, ectopic ureteroceles are frequently associated with duplex ureters, one draining the superior portion and one draining the inferior portion of the kidney. Therefore, the associated kidney has two “segments.” Grade 1 ureteroceles involve only the ureterocele segment with no ipsilateral second-segment disease. Grade 2 involves unilateral damage to both the superior and inferior renal segments, and grade 3 involves bilateral renal disease.¹⁹ This classification system has been predictive of response to surgical reconstruction of ureteroceles in humans.

The authors propose a modification of the Churchill functional classification system for dogs, for both intra-vesical and ectopic ureteroceles. There have been 10 canine ureteroceles reported in the English veterinary literature.^3–12 The Table provides a functional classification system and categorizes them accordingly, including outcome. Grade 1 ureteroceles have no concurrent ureteral or renal disease. These are often asymptomatic and infrequently diagnosed. Grade 2 ureteroceles have concomitant unilateral hydroureter, hydronephrosis, or chronic renal disease. Successful surgical correction has been shown to return these dogs to clinical normalcy. Grade 3 ureteroceles have coexisting bilateral hydroureter, hydronephrosis, or chronic renal disease. The two previously reported ureteroceles that fit grade 3 were both ectopic and, following surgery, had persistent clinical signs of renal disease.³⁵ Based on the severe renal disease in the left kidney, the significant right hydroureter and dilated renal pelves, and persistent, progressive azotemia, the dog of this report had a grade 3 intravesical ureterocele. Although clinical signs associated with the physical presence of the ureterocele have resolved, the development of azotemia and the microscopic changes in the left kidney suggest bilateral renal dysfunction.

In the opinion of the authors, a formal classification system serves three main purposes. The first, and most important, is to encourage thorough evaluation of the entire urinary tract in order to provide an accurate prognosis. It is possible that intravesical ureteroceles may be encountered incidentally during routine urinary bladder procedures, such as cystotomy for cystolith removal. Subsequently, the ureterocele may be treated appropriately during surgery but not recognized as a ureterocele until postoperative research is done. It would be helpful for the veterinary literature to indicate that a condition that appears to be limited to the urinary bladder during surgery may, in fact, occur concurrently with upper urinary tract disease or dysfunction. A cause and effect relationship between the ureterocele and renal dysfunction is not necessary for renal dysfunction to impact prognosis. In fact, renal function is the predominant predictive factor in the formal classification system. Secondly, the classification system may have benefits for the veterinarian who is preoperatively advising the owners of a dog with a suspected ureterocele. The categorized, historical information provided in the Table may be helpful in directing workup and prognosis. Finally, the proposed classification system will provide a template for the addition of future cases to the veterinary literature, allowing accurate compilation of complications and outcomes and, possibly, facilitating comparison with ureteroceles in humans.

Conclusion

This report shows that ureteroceles can occur concurrently with bilateral renal dysfunction. Therefore, after diagnosing a ureterocele, it is prudent to rule out coexisting urinary tract disease that may impact long-term success of treatment. The authors’ proposed ureterocele classification system parallels the human literature with minor modifications. This system may help to determine prognosis for ureterocele cases, lead to improved organization and reporting of individual cases in the future, and possibly allow better comparisons between treatment success of human and canine ureteroceles.

Acknowledgments

The authors thank Dr. Mike Kreuger of the Covington Veterinary Clinic in Covington, Georgia for referral of this case; Dr. Sherry Sanderson for nutritional management advice; Drs. Paul Frank and LeeAnn Pack for ultrasonography; and Drs. Angela Ford, Amy Gifford, Katherine Morgan, and David Wilkes for assistance with case management.