Abstract
Objective
To describe a novel condition in rabbits characterized by the development of septa in the urinary bladder leading to partial urinary outflow obstruction.
Methods
A multicenter retrospective case series was designed, including 7 rabbits presented from 2017 to 2023 that met 2 inclusion criteria: (1) underwent histopathology of the urinary bladder, and (2) had clinical evidence of membranes and septa in the urinary bladder through diagnostic imaging and/or necropsy. Clinical signs of urinary outflow obstruction and bladder distension were observed in all cases.
Results
Abdominal radiographs and ultrasound identified abnormalities consistent with septa in 5 of 7 and 1 of 3 cases, respectively. In all 7 rabbits, the septa were visible via rigid cystoscopy. In 6 cases, the septum developed in a dorsoventral/laterolateral plane, causing variable degrees of narrowing of the lumen of the bladder neck and accumulation of sediment cranial to it. In 1 case, the septum developed in a craniocaudal/laterolateral plane, dividing the bladder neck into dorsal and ventral portions. The most common histopathological findings in the septum included urothelial hyperplasia (7 of 7) and heterophilic, lymphocytic, and plasmocytic inflammation (5 of 7). One rabbit died while recovering from cystoscopy. In the remaining 6 cases, endoscopic removal of the septum resolved the clinical signs consistent with urinary outflow obstruction and urinary retention.
Conclusions
Rabbits can develop septa inside their urinary bladder. These benign proliferations can result in urinary outflow obstruction and urinary retention.
Clinical Relevance
Rigid cystoscopy was effective for the diagnosis and treatment of urinary outflow obstruction and urinary retention.
Urine outflow obstruction is a common pathological condition that affects many species. It can be associated with inflammatory, proliferative, and neoplastic diseases or with urolithiasis. In humans, nonneoplastic proliferative diseases of the low urinary tract are widely described and include polypoid cystitis, pseudomembranous cystitis, and cystitis glandularis.1–3 Most of these conditions are considered rare or uncommon, but in some cases, like in cystitis glandularis, they represent a precancerous condition with demonstrated progression to bladder tumors.4–6
In veterinary medicine, proliferative cystitis has been described in cats,7 dogs, and ruminants. Polypoid cystitis is reported also in dogs,8–10 cows,11 and rabbits,12 and it is an uncommon pathological condition involving the lower urinary tract. It is grossly characterized by papillomatous, multiple proliferations rising from bladder mucosa, which can be solitary, multiple, or multifocal. While in humans, it is commonly associated with longstanding indwelling urethral catheterization causing chronic bladder mucosal irritation,13 in dogs it has been mostly associated with urinary tract infections.8–10 Recently, a relationship between malignant neoplasia (transitional cell carcinoma and pseudosarcoma) of the urinary bladder and chronic polypoid cystitis has been described in 2 dogs.14,15
In small animals, recent reports7,16,17 describe a rare, unusual form of proliferative cystitis characterized by the formation of membranes of cellular debris, inflammatory cells, and clots of blood associated with severe and diffuse ulceration of the bladder mucosa with necrosis and hemorrhage. Macroscopic and histopathological features are similar to human pseudomembranous cystitis and, in cats more often than in dogs, are usually associated with urinary outflow obstruction. The causes still remain unclear, but while in humans it is mostly associated with bacterial infections, ischemia of the bladder secondary to overdistension, the effect of drugs like cyclophosphamide, and estrogenic influence,18–22 in cats the role of bacterial infections is debated. Potential etiologies in cats include feline idiopathic cystitis, hydrodistension, and subsequent chronic inflammation of the urinary bladder.7,16,17
In rabbits, urine outflow obstruction has been mostly associated with urinary sediment, urolithiasis, and neoplasia.23–25 Urinary sludge and urolithiasis are common conditions, probably in relation to particular features of calcium metabolism in this species, which make rabbits receiving a diet with a high calcium content more prone to develop hypercalciuria and urinary stones.26 Calcium carbonate monohydrate, ammonium magnesium phosphate, and anhydrous calcium carbonate crystals are common in rabbits.25,27
Urinary bladder neoplasia is rarely described in rabbits, with cases of leiomyoma and urothelial carcinoma in the current literature.23 Benign changes in the urothelium of the urinary bladder have been reported in 2 pet rabbits. Both rabbits presented with perineal urinary scalding, sludge of the urinary bladder, and ultrasonographic and endoscopic evidence of papillomatous masses on the mucosa of the urinary bladder.12 In both cases, histopathology was consistent with polypoid cystitis, but there was no evidence of urinary tract obstruction.
The purpose of this report is to describe clinical and histopathological findings of a novel proliferative disorder affecting the urinary bladder of client-owned rabbits. The condition is characterized by the formation of a partition, referred to as a “septum” in this article, which results in a variety of signs ranging from delayed urinary emptying to partial urinary outflow obstruction.
Methods
Study design and inclusion criteria
We designed a multicenter retrospective case series including rabbits who underwent histopathology of the urinary bladder and had evidence of membranes or septa in the urinary bladder. Rabbits were eligible for inclusion if they (1) underwent histopathology of the urinary bladder, and (2) had clinical evidence of membranes and septa in the urinary bladder through diagnostic imaging (radiology, ultrasonography, CT, and endoscopy) and/or necropsy.
Case search
We extracted and assessed all histopathology results of the urinary bladder from rabbits submitted by 1 institution (Clinic for Exotic Animals, Centro Veterinario Specialistico; institution 1) to a commercial laboratory (CDVet) between December 2017 and July 2023. Cases that were potentially eligible based on the first inclusion criterion were searched through the medical record databases of the institution (Vanadium Vet [Gruppo CVIT] and Provet Cloud [Nordhealth]) for assessment of the second inclusion criterion.
We extracted and assessed all histopathology results of the urinary bladder from rabbits submitted by 1 author (NDG) to a commercial laboratory (Asia Veterinary Diagnostic) between October 2017 and October 2018. Cases that were potentially eligible based on the first inclusion criterion were searched in the medical record database of the Tai Wai Small Animal and Exotic Hospital (institution 2) for assessment of the second inclusion criterion.
The “Case search” function of Cornell University Hospital for Animals (institution 3) was searched from inception to January 2024, filtering for “rabbit” and using the following strings: bladder AND membrane, bladder AND septum, bladder AND septa, bladder AND pseudomembranous.
Data extraction
The following data were collected from each case: signalment (age, sex, breed, and reproductive status), anamnesis (diet, husbandry, and previous medical history), date and reason of presentation, physical examination findings, hematobiochemical findings, diagnostic imaging findings, clinical management (medical treatment, surgical treatment, and euthanasia), details of medical treatment, details of endoscopic treatment, details of surgical treatment, outcome, histological findings, bacteriological findings (aerobic growth and anaerobic growth), results of sensitivity testing, and necropsy findings.
Reason for presentation and physical examination findings
The reason for presentation was defined as the motives for which the owners took the rabbit to the veterinarian on the admission event that generated the histologic diagnosis. For each case, the following reasons for presentation were extracted: presence of anorexia and/or hyporexia, lack of defecation, mentation (normal/lethargy/dullness), changes in urination (hematuria/pollakiuria/dysuria/anuria/strangury), presence of urinary sludge, and other reasons for presentation. The duration of clinical signs related to abnormal appetite, lack of defecation, and changes in urination was recorded. Physical examination findings were defined as the findings recorded upon hospital admission of the rabbit or, in cases of internal transfers, during the first physical examination that the primary veterinarian carried out. For each case included in the study, the following information from the physical examination was extracted when available: body weight and body condition score (BCS), rectal temperature, mentation, mucous membrane color, presence of abdominal pain, presence of a palpable mass, presence of bladder distension, other abdominal findings, presence of urine scalding dermatitis, and other general findings.
Hematologic, biochemical, urinalysis, diagnostic imaging, and microbiological findings
Individual results of hematology, biochemistry, and/or blood gas analysis were extracted and tabulated. Each animal was characterized as normal or abnormal based on recently published reference intervals (RIs) for client-owned rabbits.28–31 For each radiographic study, information extracted from the records included the presence and distribution of sludge in the urinary bladder, presence of urinary stones, presence of overdistension of urinary bladder, visualization and localization of visible septa or membranes in the urinary bladder, and other findings. For ultrasound studies, information extracted from the records included the presence of urinary sludge and urinary stones, thickening or abnormalities of the wall of urinary bladder, peritoneal reactivity around the urinary bladder, presence of abdominal free fluid, presence of urinary sludge or stones, visualization and localization of visible septa or membranes in the urinary bladder, ultrasound diagnosis, and other findings. For urinalyses, the method of collection (cystocentesis and voided catch) and the results were extracted, including urine protein-to-creatinine ratio, which was compared to published RIs for rabbits.32 For each patient, microbiological analyses, including methods for collection (cystocentesis, bladder mucosal swab, bladder mucosal biopsy, and urolith culture) and results (bacterial growth, isolate identification, and antimicrobial susceptibility), were extracted.
Diagnostic testing performed more than 14 days before the urinary bladder sample that resulted in the histological diagnosis was not included. When multiple studies with the same diagnostic tool were performed on the same rabbit, the study closer in terms of timing to the histologic diagnosis was reported in the results, and studies further away from the histologic diagnosis were mentioned in comparison to those.
Endoscopic procedures, surgical procedures, and medical management
For each endoscopic procedure, information extracted included instruments used (type and dimension of endoscope), air or saline solution infusion, instruments used for endoscopic guided procedures, and type of procedure performed. For each endoscopy, information extracted from the records included the presence and distribution of urinary sludge and stones, visualization and localization of visible septa or membranes in the urinary bladder, any cystitis-related signs, and other findings. For each surgical procedure performed, information extracted included the surgical technique used to perform cystotomy. Medical treatments administered to rabbits were extracted and categorized into the following classes: antimicrobials, opioids, NSAIDs, corticosteroids, fluid therapy, and miscellaneous. The names of the specific active principles administered were extracted.
Histopathologic and necropsy findings
The method for collection and results of histopathology of the urinary bladder for each patient included were extracted and tabulated. If a necropsy was performed, the following data were collected: macroscopically visible alterations in the urethra, urinary bladder, ureters, kidneys, and alterations in other organs.
Outcome
For each case included in the study, data about the outcome within 12 months after the end of the study period (July 2023) were extracted, with a particular focus on the recurrence of the associated clinical signs of the low urinary tract (hematuria, pollakiuria, dysuria, strangury, anuria, and urinary sludge) and results of any diagnostic procedure (radiology, ultrasonography, CT scan, and endoscopy) involving the urinary tract that was carried out after the discharge.
Data reporting
Categorical data were reported as count data with the number of animals for which the data were available. Continuous data were reported as medians and IQRs.
Results
Patient inclusion
Eight histopathologic samples of the urinary bladder of rabbits from institution 1 fulfilled the first inclusion criteria. One histopathology was consistent with urothelial carcinoma and was obtained during a postmortem of a rabbit with a neoformation occupying the majority of the urinary bladder lumen. The mass was spherical with a large base, not consistent with a membrane or septa, and for this reason, the case was not included in the study. A second sample was obtained via an endoscopic biopsy from a proliferative, sessile, pedunculate, papillomatous neoformation on urethral mucosa, and histopathology was consistent with chronic lymphocytic cystitis. The proliferative structure was not macroscopically consistent with a membrane or septum, and for this reason, this case did not meet the second inclusion criterion and was excluded from the study. From institution 2, 1 histopathologic sample of the urinary bladder of a rabbit fulfilled the first and second inclusion criteria. From institution 3, 1 case fulfilled the second inclusion criteria, but the endoscopic biopsy obtained was nondiagnostic due to the small size. As such, no cases were included from this institution.
In total, 7 histopathologic examinations fulfilled both inclusion criteria from 2 institutions and were included in the study (Supplementary Table S1).
Signalment, reason for presentation, and physical examination findings
Of the 7 rabbits included, 4 were Mini Lops, 2 were Lionheads, and 1 was a mixed-breed dwarf rabbit. Four were neutered males, 1 was an intact male, 2 were neutered females, and the age was from 2 to 8 years. The weight ranged from 1.3 to 3.0 kg with a BCS 2/5 (n = 1), 3/5 (1), 4/5 (4), and 5/5 (1).
All the rabbits lived indoors and were fed with commercial pellets for rabbits and mixed vegetables. Except for case 5, all of them received mixed hay, and case 7 was fed also alfalfa hay.
All rabbits were presented for anorexia/hyporexia, decreased activity or lethargy, and had clinical signs associated with urinary tract disease including dysuria and stranguria observed from 12 hours to 1 month before presentation. The owners of 5 rabbits reported the presence of urinary sludge in the urine. No rabbit presented hematuria.
On physical examination, 3 cases were hypothermic (cases 3, 5, and 6) based on rabbit reported RIs.33 All rabbits had abdominal discomfort and distension of the urinary bladder. Five rabbits exhibited mild-to-severe urine scalding of the perineal area, and 1 of them had a coexisting inguinal hernia involving the right testicle associated with peripheral subcutaneous edema of the hindlimbs (case 5). The rest of the physical examination was unremarkable.
Hematobiochemical and diagnostic imaging findings
For all cases, a CBC and chemistry panel was available.
Results for CBC were within published ranges for pet rabbits, except for case 3, which presented a relative erythrocytosis (47%; RI, 20.6% to 39.6%). All the rabbits presented elevated serum total calcium concentration (range, 12.5 to 14.7 mg/dL; RI, 7.6 to 12.2 mg/dL) and elevated serum ALP concentration (range, 24 to 76 U/L; RI, 6 to 14 U/L). Cases 3 and 6 presented hyperglycemia (407 and 274 mg/dL, respectively; RI, 109 to 161 mg/dL). Case 3 had elevated albumin concentration (4.5 g/dL; RI, 2.8 to 4.0 g/dL). Cases 5 and 6 had low albumin concentration (2.5 and 1.9 g/dL, respectively) and low total protein concentration (5.0 and 5.9 g/dL, respectively; RI, 6.1 to 7.7 g/dL). Case 5 had moderately elevated ALT (122 U/L; RI, 52 to 80 U/L).
Abdominal radiographs on 2 views (right lateral and ventrodorsal) were obtained in every rabbit. All rabbits had a full urinary bladder, and in 5 rabbits, the bladder was subjectively considered overdistended, that is, larger than expected compared to the size of the abdomen. Various degrees of increased radiopacity at the level of the urinary bladder consistent with urinary sludge were visible in all cases. In 5 cases, a filling defect in urinary sludge was visible at the level of the urinary bladder neck on lateral radiographs (Figure 1). One case also presented a 3.9-mm rounded, radiopaque, irregular structure in the lumen of the urinary bladder consistent with a urolith. Other radiological findings included mild to moderate gastric gas distention in 3 cases, mild diffuse intestinal gas distension in 1 case, and loss of definition of all the abdominal structures consistent with peritoneal effusion.
A and B—Representative lateral abdominal radiographs of rabbits diagnosed with a septum at the level of the urinary bladder neck, developing on the dorsoventral/laterolateral plane, and urinary bladder sludge for case 1 (A) and case 6 (B). Images magnified and increased in contrast are provided for better visualization of the septum (arrows) on the right of the original radiographs. The septum is visible as a filling defect in the urinary sludge.
Citation: American Journal of Veterinary Research 2025; 10.2460/ajvr.25.03.0101
Abdominal ultrasonography was performed in 3 cases. In case 1, a septum originating from the wall of the urinary bladder was identified cranially to the bladder neck, causing an apparent compartmentalization of the lumen (Figure 2). Color flow Doppler identified a passage of urine between the compartments of the bladder divided by the septum, confirming a communication from them (Supplementary Video S1). In cases 3 and 5, the wall of the urinary bladder was considered normal and no membranes or septa were identified. In both cases, ultrasound detected urinary sludge and subjective overdistension of the urinary bladder. In case 3, additional ultrasonographic findings included gastrointestinal meteorism and bilateral focal mineralization of kidneys. In case 5, other findings included a small amount of peritoneal free fluid, left ureteral ectasia, subjective enlargement of the sexual accessory glands, and right inguinal hernia with a herniated testicle. The right testicle was larger than the left, with a heterogeneous parenchyma with multiple foci of mineralization.
A—Ultrasonography of the urinary bladder in case 1. Note partitioning of the lumen caused by a septum originating from the wall of the urinary bladder and developing on a dorsoventral/laterolateral plane. B—Color flow Doppler of the same rabbit showing the presence of communication between the 2 compartments of the urinary bladder defined by the septum. Cranial and ventral areas of rabbits are indicated.
Citation: American Journal of Veterinary Research 2025; 10.2460/ajvr.25.03.0101
Diagnostic endoscopy
Cystoscopy was performed in all cases. A rigid, 2.7-mm, 30° view telescope, enclosed in a 14.5-French operative sheath with a 5-French working channel and 2 stopcocks for irrigation (Karl Storz SE & Co KG), was used to access the urinary bladder as previously described.12 For all the cases, the procedure was carried out under general anesthesia.
Sterile warmed saline solution (0.9% NaCl) was irrigated throughout the procedure. In all cases, the presence of at least 1 membrane or septum was identified. In all cases, a septum was present at the junction between the neck of the urinary bladder and the inlet of the urethra. In cases 1, 2, 4, 6, and 7, the septum appeared to be extending centripetally from the mucosa, on a dorsoventral/laterolateral plane, causing a moderate to severe reduction of the lumen of the urinary bladder neck (Figure 3). In case 3, the septum developed on a craniocaudal/laterolateral plane, dividing the inlet of the urethra into 2 portions.
Urinary endoscopy showing variable conformation of the septum (Se) and variable reduction of the lumen of the urinary bladder in affected rabbits. The portion of the urinary bladder cranial to the septum is indicated by an asterisk. A—Septum with a centripetal extension from the mucosa, on a dorsoventral/laterolateral plane (case 2). Notice the thick urinary bladder sludge trapped in the cranial portion of the bladder by the septum. B—Septum developing on a craniocaudal/laterolateral plane, dividing the inlet of urethra in a ventral and dorsal portion (case 3). C—Septum with a centripetal extension but thicker and less developed than other cases, resulting in a lower reduction of the lumen (case 5). D—Endoscopic photograph obtained during diode laser ablation of the septum (case 2).
Citation: American Journal of Veterinary Research 2025; 10.2460/ajvr.25.03.0101
In case 5, the septum had a similar conformation to cases 1, 2, 3, 6, and 7 but was thicker and less developed, resulting in a lower reduction of the lumen of the urinary bladder neck (Figure 3). Multiple white, sessile, pedunculated, different-sized polyps were visible originating from the urethral mucosa in this case, causing a major reduction of the lumen.
Little to abundant amount of urinary sludge was identified in the lumen of the urinary bladder in all cases. In cases 1, 2, and 7, an accumulation of dense and thick sludge appeared intermittently obstructing the lumen of the septum during the endoscopic procedure, preventing normal urine outflow (Supplementary Video S1). In case 4, endoscopy confirmed the presence of a urolith in the urinary bladder. In cases 1, 2, 6, and 7, the urine that flowed out from the urinary bladder appeared dark and malodorous.
Endoscopic procedures, surgical procedures, and medical management
During cystoscopy, the identified septum was biopsied using a 34-cm-long flexible biopsy forceps with double-action jaws in all cases. In case 5, a biopsy of the urethral polyps was also performed using the same type of instrument. In cases 1, 3, 6, and 7, following the endoscopic biopsy, a 34-cm-long flexible grasping forceps with double-action jaws were used for gentle debridement of the septum. In case 5, the same procedure was carried out to remove the larger polyps originating from the urethral mucosa. In cases 2 and 4, a diode laser (Velure S9; Lasering SGL) was used for ablation of the septum (Figure 3). In case 4, after ablation of the septum, removal of the urinary stone was performed using a 60-cm-long flexible stone basket. In all the rabbits, the urinary bladder was lavaged through irrigation with a warmed saline solution (0.9% NaCl) multiple times until the voided fluid appeared clear and free from sediment.
After the endoscopic procedure and in the same anesthetic event, case 5 underwent hernia reduction, inguinal herniorrhaphy, and bilateral orchiectomy through a laparotomic approach. Both the testicles were fixed in 10% buffered formalin and submitted for histopathology.
All the cases received medical treatments, including opioids (methadone and/or buprenorphine, various formulations and doses, all the cases), NSAIDs (meloxicam, various formulations and doses, all the cases), ranitidine (case 6), fluid therapy with lactated Ringer (all cases) and with 2.5% glucose supplement (case 5), and Phyllanthus niruri supplement (Niruri; Dinamys SAS; cases 4, 5 and 7). In cases 3, 5, and 7, a daily cleaning with neutral shampoo of the perineal area was performed to treat urinary scalding. Cases 2, 3, 4, 5, and 6 received assisted feeding following the procedure. All the rabbits received antimicrobial treatment, including enrofloxacin (cases 1, 2, 4, and 7), enrofloxacin and metronidazole (case 5), marbofloxacin and benzylpenicillin (case 3), and trimethoprim/sulfamethoxazole (case 6). Case 5 received an infusion with human serum albumin (50 g/L Grifols; Istituto Grifols) to correct hypoalbuminemia and mefepronic acid (Hepagen; Fatro SPA) to support liver function.
Urinalysis, microbiological findings, and sensitivity testing
Urinalysis was performed only for case 3, and urine collection was carried out by cystocentesis. For urine culture, the sample was stored in a 3-mL urine tube with boric acid and processed within 24 hours. In this case, urinalysis reported a mild increase of urine specific gravity, with a value of 1.038 (normal range, 1.003 to 1.036), and was positive for the presence of protein, and blood. Urinary sediment examination reported several calcium carbonate crystals, leukocytes, erythrocytes, and several cocci. The urine protein-to-creatinine ratio was elevated (1.4; RI, 0.11 to 0.4). Aerobic and anaerobic urine culture was positive for Enterococcus faecalis and Pseudomonas aeruginosa. In case 6, a urine culture was performed when first presented following urine collection via cystocentesis. The culture was negative for aerobic and anaerobic organisms.
Outcome
Data about the outcome were available for all cases. Case 1 showed strangury and dysuria after recovery from the endoscopic procedure, with a complete resolution of urinary symptoms observed within 48 hours. No more clinical signs associated with the lower urinary tract were reported by the owner. The rabbit was euthanized 3 years following the initial diagnosis for complications related to a thymoma. Case 2 died during recovery from anesthesia at the end of the endoscopic procedure. Case 3 was discharged 4 days after the endoscopic procedure. The rabbit had mild stranguria and hematuria during the first 2 days of hospitalization, which resolved before discharge. It was presented again 11 months after the initial diagnosis of respiratory distress. On that occasion, the owner did not report any visible clinical signs related to lower urinary tract disease since discharge. Abdominal ultrasonography showed bilateral focal renal mineralization, urinary bladder sludge, and moderate intestinal meteorism. The rabbit had progressing respiratory signs and died 2 days after admission. A postmortem examination was not allowed. Case 4 showed dysuria and stranguria for the first 24 hours following the endoscopic procedure that resolved in the following days leading to discharge on day 3 of hospitalization. The rabbit presented again 40 days following discharge for an episode of acute anorexia and lack of defecation, which resolved with medical treatment. On that occasion, the owner did not report any clinical signs related to a recurrence of the lower urinary tract disease. Abdominal radiographs showed a small amount of urinary sludge in the urinary bladder. Case 5 died during hospitalization for 2 days following the endoscopic and surgical procedures likely due to sepsis. The rabbit developed persistent hypoglycemia, worsening hypoalbuminemia, and peripheral subcutaneous edema, regardless of medical treatment, including human serum albumin infusion. A postmortem examination was not performed. Case 6 was discharged 2 days after the endoscopic procedure with normal urine production and with remission of clinical signs. The rabbit was presented again 4 months following discharge and diagnosed with urinary bladder and urethral uroliths through radiographs. A urine sample was collected via cystocentesis for urinalysis. Urine sediment analysis was positive for WBCs and struvite. Aerobic and anaerobic urine culture grew Listeria welshimeri. Cystotomy was performed to remove the 4 uroliths following retrograde catheterization of the urethra with an 18-French Foley catheter. The septum that had previously been visualized and removed endoscopically was not observed during the cystotomy. A second biopsy of the bladder mucosa was collected and submitted for histopathology, which was consistent with severe erosive to ulcerative subacute cystitis with edema. The rabbit was discharged following this event without complications. The rabbit died 4 years later of complications associated with a thymoma. During this period, the rabbit showed persistent urinary sludge, but no clinical signs associated with lower urinary tract obstruction. Case 7 showed stranguria and hematuria for the first 24 hours following the endoscopic procedure, with a complete resolution of urinary signs within 72 hours following the endoscopic procedure. The owner was contacted 15 months following the initial presentation to inquire about the status of the rabbit, and they did not notice the recurrence of clinical signs.
Histopathology and necropsy
On histopathological examination of the biopsied tissue, all samples exhibited urothelial hyperplasia. Evidence of inflammation, characterized by heterophils, lymphocytes, and plasma cells in the mucosal lamina propria, was identified in 5 cases (1, 3, 4, 6, and 7). Papillary projections fusing together and forming a septum were observed in 3 cases (2, 5, and 7). In case 5, muscular fibers were evident within the septum. Edema and mineralization of the lamina propria were noted in 2 cases (2 and 6).
A necropsy was performed on case 2, the patient who died at the end of the endoscopic procedure. Upon necropsy, the urinary bladder appeared subjectively distended. The mucosal surface was irregular, with small papillary projections. The mucosal septum visualized upon endoscopy was grossly visible at the level of the neck of the bladder and resulted in a stricture of approximately 2 mm in diameter (Figure 4). No other macroscopic abnormalities were noticed. The cause of death was attributed to anesthetic complications. A full-thickness histological examination of the bladder septum revealed a layered structure, with urothelium present on both sides of the septum, resting on a core of fibrillar collagen.
Gross and histopathologic appearance of urinary bladder septa in rabbits. A—Gross appearance of the urinary bladder during necropsy in case 2. The mucosal surface appears irregular with small papillary projections. The septum causes a stricture at the level of the neck of the urinary bladder, which only allows the passage of a 1-mm metallic probe. B—Representative histopathological image of urothelial hyperplasia, with a papillary projection composed of a core of fibrillar collagen covered by hyperplastic urothelium. On the luminal surface, granular mineral material is observed.
Citation: American Journal of Veterinary Research 2025; 10.2460/ajvr.25.03.0101
Discussion
In this case series, we report for the first time a proliferative disorder of the urinary bladder of the rabbit characterized by the formation of a septum, which was associated with reduced urine outflow and clinical and diagnostic evidence of urine retention. Based on macroscopic and microscopic features, this presentation appears distinct from other proliferative disorders of the urinary tract previously reported in rabbits and other species. Polypoid and pseudomembranous cystitis are benign proliferative conditions of the urinary bladder that affect animals. Polypoid cystitis is characterized by white-to-transparent, sessile, spheroidal masses protruding into the lumen.12 Pseudomembranous cystitis, described in dogs, cats, and humans, involves thickening of the urinary bladder wall with fibrin-hemorrhagic tissue adhering to the mucosa, blood clots, and necrosis.7 These features were absent in the 7 cases presented in this report.
The rabbits in this report exhibited clinical signs consistent with lower urinary tract disease. In most instances, diagnostic imaging revealed urinary bladder overdistension. Additionally, endoscopy showed dark, malodorous urine, indicative of urine stasis. Except for case 5, the septum in all rabbits significantly reduced the urethral inlet, leading to decreased urine outflow. In all cases, at least one edge of the septum was located at the neck of the urinary bladder, where it joins the urethra, forming a narrowing that obstructs urine flow. Its consistent presence in this region may explain the significant clinical impact, primarily characterized by reduced urine outflow. Notably, ablation of the septum resolved clinical signs in the 5 rabbits that have long-term follow-up. Various amounts of urinary sludge in the urinary bladder were present in all rabbits. The distribution of the sludge suggested compartmentalization of the urinary bladder on abdominal radiographs, since the sludge was accumulating in the cranial aspect of the organ. Additionally, the urinary sludge served as a positive contrast allowing visualization of the septum in certain cases. It is unclear whether the sludge is a predisposing factor for the development of urinary septa, a consequence of them, or an accidental finding. In multiple cases, it was observed that the septum allowed minimal urine flow while hindering the emission of thicker particles, resulting in the retention of debris in the bladder. This aspect was dynamically observed during cystoscopy and abdominal ultrasound. Urinary sludge and urolithiasis have frequently been associated with lower urinary tract obstruction in rabbits.24,25 The combination of the septum and the presence of urinary sludge or stones could lead to a complete obstruction of the lower urinary tract. On the other hand, it is believed that urinary sludge in rabbits could result in chronic inflammation of the bladder.12 Histopathology confirmed the presence of inflammatory cell infiltration, supporting the hypothesis of an inflammatory process. The role of chronic inflammation in proliferative and neoplastic disorders of the urinary tract has been recognized in many species, including humans, dogs, cats, and rats.7,14–17,34,35 For example, in humans, polypoid cystitis has been linked to prolonged indwelling urethral catheterization, which causes chronic bladder mucosal inflammation. In cats, chronic inflammation resulting from urinary bladder overdistension and feline idiopathic cystitis has been implicated in the development of pseudomembranous cystitis.17 In a similar way, there could be a relationship between chronic irritation caused by urinary sludge and the proliferative disorder observed in these 7 cases.
Proliferative disorders of the lower urinary tract have also been associated with infectious etiologies in many species, including bacterial and parasitic infections. For example, polypoid cystitis in dogs has been linked to bacterial urinary tract infections.9,10 In a study by Martinez et al,17 61% of urine cultures tested positive, with the most commonly isolated bacteria being Proteus spp, followed by Escherichia coli, Staphylococcus spp, and Enterococcus spp. In rats, infection by Trichosomoides crassicauda has been associated with histopathological changes in the urinary bladder, including inflammation, moderate-to-severe epithelial hyperplasia, and metaplasia.36,37 However, mycotic and viral urinary tract disorders are considered rare in humans, sparsely described in veterinary medicine, and generally not associated with proliferative disorders.38
In this study, only 2 cases underwent urine culture. The first (case 3) tested positive for E faecalis and P aeruginosa. The second (case 6) initially yielded a negative culture, but 4 months later, a follow-up culture tested positive for L welshimeri. Rabbits have been used as an experimental model for studying bacterial cystitis in women,39 but there is limited information on spontaneous bacterial lower urinary tract infections in this species. Bacteria were not observed in the histopathological samples. Furthermore, even if no specific staining was carried out, there were no histopathological features indicative of viral, mycotic, or parasitic infections. However, this does not entirely exclude an infectious etiology. Except for case 2, biopsy samples from the urinary bladder were obtained during endoscopy. While endoscopic biopsy is generally considered a viable technique to obtain samples from the urinary bladder,12 this technique is limited by the collection of relatively small samples originating from the superficial layers of the biopsied tissue. Therefore, it is not possible to rule out the presence of an infectious agent or associated histopathological changes in the deeper layers of the bladder or the septum, especially in light of the presence of inflammatory infiltrates mainly composed of heterophils in certain septa. Even if a bacterial infection as a primary cause for this condition is unlikely, the concurrent presence of a bacterial infection in these cases is possible. A common aspect in all the cases of this study was urine stasis and retention secondary to the presence of the septum and the urinary sludge. Urinary stasis is considered a risk factor for urinary tract infections in humans,40 dogs, and cats.34 If possible, a urine culture should be always carried out in rabbits with clinical signs attributable to lower urinary tract disease.
It is interesting to notice that in case 5 the histological changes were limited to the formation of the mucosal septum with the presence of muscular fibers in the septal wall. It is possible that the etiology of the septa observed in these cases varies, and in this specific case, a congenital malformation could be possible. In human medicine, duplication and septa of the urinary bladder are considered a rare congenital condition that consists in the presence of a partial or complete compartmentalization of the urinary bladder with different morphological abnormalities of the urethra, ureter, and kidneys. This malformation has been mainly, but not exclusively, described in young people and is usually associated with other congenital abnormalities of the genital and distal intestinal tract.35,38,41 These features were not identified in case 5, but a congenital malformation cannot be completely ruled out in this rabbit.
The small sample size of this study does not allow the identification of predisposing factors in terms of age, sex, and breed. The age of the rabbits ranged from 2 to 8 years, supposing that this disease affects mainly adult and mature animals. Four of the cases were neutered males, 1 was an entire male, and 2 were neutered females. In other small exotic species, a sex predisposition has been reported for lower urinary tract diseases. For example, male chinchillas and guinea pigs are more prone to develop urolithiasis than females,42,43 whereas urinary tract infections are more frequent in female guinea pigs.42 In rabbits a sex predisposition in low urinary tract disease has not been identified, except for inguinal herniation of urinary bladder, which is more frequently reported in males.24 Moreover, 4 rabbits were Mini Lops, 2 were Lionheads, and 1 was a mixed-breed dwarf rabbit. There is no evidence of breed predisposition in lower urinary tract disease in rabbits, and the higher number of Mini Lops in this study may reflect the actual popularity of this breed instead of the others. Four cases presented a BCS higher than 3/5. Obesity affects pet rabbits with different prevalence based on geographical variation,44 and one study45 suggests a higher predisposition of neutered rabbits. Overweight and obesity have been associated with lower urinary tract disease in rabbits, such as urine retention, urinary sludge, cystitis, and urine scalding.44,46 It is unlikely that elevated body condition is the direct cause of the changes observed in these animals but cannot be ruled out.
In this study, the main hematobiochemical findings concerned serum total calcium and ALP, which were higher than RIs in all the cases. Due to the unique calcium metabolism in rabbits than other mammalian species, a diet with high calcium content may result in an increase of serum total calcium and renal calcium excretion, predisposing the patient to hypercalciuria and urolithiasis.26,47 For this reason, it is likely for rabbits with urolithiasis and hypercalciuria to present high serum calcium concentration.48 All 7 cases of this study presented evidence of urinary sludge and/or urolithiasis by diagnostic imaging and endoscopy, and this can justify the increase of total calcium at biochemistry in all these rabbits.
This study has several limitations. Due to the retrospective design of the study, not all of the information planned to be extracted was available for all cases. Furthermore, only 2 cases underwent urine analysis and bacteriological culture. Finally, none of the cases underwent contrast-enhanced CT, which could have helped highlight the dynamic nature of the obstruction.
In conclusion, the formation of a septum into the urinary bladder should be included in the differential diagnosis of rabbits with clinical signs suggestive of lower urinary outflow obstruction. Abdominal radiographs can assist in the diagnosis of this condition when urinary sludge is present. Endoscopy was effective in obtaining a definitive diagnosis, and endoscopic treatments seemed to be effective in the cases included. Further studies are needed to understand the pathogenesis of this disease and the long-term effectiveness of the endoscopic approach and ablation of the septum.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org.
Acknowledgments
The authors thank the late Dr. Drury Reavill for performing the histopathological analysis of one of the cases and for valuable discussions regarding this condition. The authors thank Dr. Annalisa Nicoletti and Ulrich Zeyen for the abdominal ultrasound in case 1.
Disclosures
The authors have nothing to disclose. No AI-assisted technologies were used in the composition of this manuscript.
Funding
The authors have nothing to disclose.
ORCID
Giulia Bersanetti https://orcid.org/0009-0009-4364-3501
Nicola Di Girolamo https://orcid.org/0000-0001-5203-9765
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