Emphysematous Cystitis and Pyelonephritis in a Nondiabetic Dog and a Diabetic CatS
Emphysematous cystitis (EC) and emphysematous pyelonephritis (EPN) are the result of infection of the urinary bladder and kidneys by gas-producing microorganisms. Those infections are most often reported in diabetic patients and rarely occur concurrently. This article describes two cases of concurrent EC and EPN, one in a nondiabetic dog and the other in a diabetic cat. The use of diagnostic imaging is necessary in the diagnosis of emphysematous infections. Both radiography and ultrasonography were used in the diagnosis of EC and EPN in the patients described in this report.
Introduction
Emphysematous cystitis (EC) and emphysematous pyelonephritis (EPN) are uncommon infections of the urinary tract. They are caused by gas-producing organisms and are characterized by the presence of gas within the urinary bladder wall, bladder lumen, renal collecting system/parenchyma, and perirenal tissues. In humans, these infections are most often reported in diabetic patients.1,2 Slightly more than half (15 of 26) of the EC cases reported in the veterinary literature have occurred in animals with underlying diabetes mellitus.3–12 To date, there is only a single known report of a veterinary patient with concurrent EC and EPN.3 Two additional cases of concurrent EC and EPN, one involving a nondiabetic dog and the other a diabetic cat, are described in this report.
Case Report
Case 1
A 10 yr old spayed female miniature schnauzer weighing 4.3 kg presented with a 1 wk history of weakness that had progressed to recumbency. According to information provided by the referring veterinarian at the time of presentation, the patient was suspected to have hyperadrenocorticism based on an elevated cortisol level obtained 3 mo prior to referral. The dog had been treated at one time with selegilinea, but was not receiving that medication at the time of referral. There was also a history of recurrent urinary tract infections, which had been treated with, and responded to, antibiotics.
On initial physical exam, the patient was cachectic (body condition score of 1.5 out of 5) and dehydrated. Temperature, pulse, and respiration were within normal limits. A grade 2 out of 6 systolic murmur was detected with the point of maximum intensity on the left. Blood work revealed a leukocytosis with a left shift (46.6 × 109/L; reference range, 6.0–17.0 × 109/L) with 1.9 109/L bands (reference range, 0–0.3 × 109/L), a mild hyperglycemia (7.2 mmol/L; reference range, 3.3–6.7 mmol/L), azotemia (blood urea nitrogen [BUN] was 57.3 mmol/L; reference range, 5.7–21.4 mmol/L and creatinine was 256 µmol/L; reference range, 44–124 µmol/L), hypoalbuminemia (28 g/L; reference range, 30–45 g/L), hypercholesterolemia (13.6 mmol/L; reference range, 3.2–8.7 mmol/L), and an elevated creatine kinase (28 µkat/L; reference range, 0.97–4.0 µkat/L). Multiple electrolyte abnormalities were also noted, including hyperphosphatemia (4.4 mmol/L; reference range, 0.7–2.1 mmol/L), hypokalemia (3.6 mmol/L; reference range, 3.8–5.5 mmol/L), and hypochloremia (97 mmol/L; reference range, 109–124 mmol/L). In addition, elevations of alanine aminotransferase (1.9 µkat/L; reference range, 0.2–1.3 µkat/L) and alkaline phosphatase (23 µkat/L; reference range, 0.2–2.0 µkat/L) were detected. Urinalysis, obtained by cystocentesis, revealed a urine specific gravity of 1.012, proteinuria (2+ out of 3+), pyuria (10–50 WBCs/high-power field [hpf]), hematuria (10–50 red blood cells/hpf), and a large amount of bacteria (bacilli). A urine sample was submitted for culture and sensitivity.
The patient was hospitalized and started on IV fluidsb with 16 mEq potassium chloride/L at rate of 40 mL/hr. IV enrofloxacinc (5.8 mg/kg IV q 12 hr for the first 24 hr, then 11 mg/kg IV q 24 hr) and ampicillind (28 mg/kg IV q 8 hr) were also initiated, pending results of urine culture and sensitivity.
Initial diagnostic imaging included thoracic and abdominal radiographs and abdominal ultrasound. Thoracic radiographs were unremarkable. Numerous focal gas opacities were detected within the wall of the urinary bladder on abdominal radiographs as well as gas superimposed over both kidneys (Figure 1). Ultrasound examination of the abdomen showed hyperechoic foci with reverberation artifact within the bladder wall, consistent with intramural gas (see Supplementary Video I). Multiple hyperechoic foci were present in the renal cortices. In addition, hyperechoic foci with reverberation artifact indicative of gas were present in the collecting system of each kidney (see Supplementary Video II). Echogenic swirling material was present in the urinary bladder consistent with either cellular or proteinaceous debris. The adrenal glands were within normal limits for size and unremarkable in shape. Numerous linear hyperechoic foci were present in the spleen, which were most consistent with either fibrosis or mineralization. The liver was hyperechoic with numerous variably sized, poorly circumscribed, hypoechoic, and isoechoic nodules. Hyperechoic foci were present in the gravity-dependent portion of the gall bladder. The remainder of the ultrasound examination was unremarkable. Based on blood work, urinalysis, and imaging results a diagnosis of concurrent EC and EPN was made.
Citation: Journal of the American Animal Hospital Association 50, 2; 10.5326/JAAHA-MS-5972
Subsequent blood work (performed 24 hr after initial presentation) revealed a mild decrease in the leukocytosis (31.3 × 109/L; reference range, 6.0–17.0 × 109/L), a reduced BUN (32 mmol/L; reference range, 5.7–21 mmol/L), an increased creatinine (327 µmol/L; reference range, 44–124 µmol/L), a decreased albumin (22 g/L; reference range, 30–45 g/L), an increased creatine kinase (65.5 µkat/L; reference range, 0.97–4.0 µkat/L), and a reduction in phosphate (2.5 mmol/L; reference range, 0.7–2.1 mmol/L). Alanine aminotransferase and alkaline phosphatase were persistently elevated. All other parameters had returned to normal.
Abdominal ultrasonography was repeated 2 days following initial presentation. The amount of gas visualized within the urinary bladder wall and renal collecting systems was subjectively decreased. There was no change associated with the hyperechoic foci within the renal cortices or the appearance of the liver and spleen.
Urine culture was positive for Escherichia coli (E. coli) and Enterobacter cloacae, both of which were found to be resistant to enrofloxacin and ampicillin. The antibiotic therapy was changed to imipeneme (8 mg/kg IV q 8 hr) on the third day of hospitalization. The patient developed anuric renal failure that was unresponsive to both furosemidef and dopamineg administration and died in the hospital 4 days after presentation. A necropsy was not performed.
Case 2
A 9 yr old spayed female domestic shorthair weighing 3.2 kg presented with a 2 wk history of polyuria, polydipsia, lethargy, and inappropriate urination. On initial physical exam, the patient was lethargic, dehydrated, and had pale and tacky mucus membranes. Temperature, pulse, and respiration were within normal limits. Hard feces were detected on abdominal palpation.
Initial diagnostics included a complete blood count, serum biochemical profile, urinalysis, and abdominal radiographs. Blood work abnormalities included leukocytosis (26.6 × 109/L; reference range, 5.5–19.5 × 109/L) with a left shift (0.5 × 109/L; reference range, 0–0.3 × 109/L), and a normochromic normocytic anemia (packed cell volume was 24%; reference range, 30–45%). Serum biochemical profile showed significant hyperglycemia (31 mmol/L; reference range, 3.3–7.4 mmol/L), mildly elevated BUN (55 mmol/L; reference range, 11.4–25 mmol/L), mildly elevated creatinine based on the International Renal Interest Society guidelines (150 µmol/L; reference range, 70–185 µmol/L), mild hyperproteinemia (90 g/L; reference range, 63–86 g/L), mild hyperphosphatemia (2.3 mmol/L; reference range, 0.9–2.1 mmol/L), moderate hyponatremia (136 mmol/L; reference range, 150–163 mmol/L), and mild hypochloremia (108 mmol/L; reference range, 108–118 mmol/L). There were also multiple abnormalities found on urinalysis (obtained by cystocentesis), including a urine specific gravity of 1.016, glycosuria (3+ out of 3+), pyuria (> 100 leukocytes/hpf), proteinuria (2+ out of 3+), hematuria (3+ out of 3+), and many bacilli. A urine sample was submitted for culture and sensitivity.
Abdominal radiographs revealed multiple round to linear gas opacities within the mildly enlarged right and left renal silhouettes. A well-circumscribed centrally located gas opacity measuring 2.5 cm in diameter was present within the moderately distended urinary bladder with multiple small mildly indistinct gas opacities surrounding it. There was mild distension of the stomach and small intestines. The colon contained a large amount of fecal material (Figure 2).
Citation: Journal of the American Animal Hospital Association 50, 2; 10.5326/JAAHA-MS-5972
Based on lab work and imaging abnormalities, a diagnosis of diabetes mellitus with concurrent EC and EPN was made. The patient was treated at home by the owner with glargineh [0.3 U/kg subcutaneously (SC) q 12 hr] and was administered one antibiotic injection of cefovecin Nai (8 mg/kg SQ). The patient was also started on a commercial prescription dietj for management of diabetes.
The patient initially responded favorably to treatment with a decrease in polydipsia; however, 4 days following initial presentation, the patient returned for a follow-up examination because of an episode of vomiting and increased lethargy. A complete blood count and serum biochemistry profile were repeated, which showed an increase in severity of hyperglycemia (40 mmol/L; reference range, 3.3–7.4 mmol/L), azotemia (BUN was 87 mmol/L; reference range, 11.4–25 mmol/L and creatinine was 194 µmol/L; reference range, 70–185 µmol/L), persistent anemia (hematocrit was 23%; reference range, 30–45%), and normal leukocyte count (18.8 × 109/L; reference range, 5.5–19.5 × 109/L) with persistently increased band neutrophils (1.7 × 109/L; reference range, 0–0.3 × 109/L).
The patient was hospitalized. Treatment included glargine (0.6 U/kg SC q 12 hr), fluid therapy with 16 mEq potassium chloride/L), and ampicillin Na/sulbactam Nak (33 mg/kg IV q 8 hr). During that time, results of the previously submitted urine culture showed abundant growth of nonhemolytic E. coli and α-hemolytic Streptococcus spp. Both organisms were susceptible to the cefovecin and ampicillin Na/sulbactam Na. Over the course of hospitalization, the hyperglycemia resolved but the patient experienced intermittent fever and multiple lacerations secondary to fragile skin syndrome.
Due to the fever and fragile skin, an abdominal ultrasound was performed on the fifth day of hospitalization (10 days following initial presentation). Gas was not detected in either the urinary bladder or kidneys; however, the kidneys were enlarged with hyperechoic cortices, irregular margins, and decreased corticomedullary definition. Mild (i.e., 2 mm) dilation of the right renal pelvis was observed. Two well-defined, thick-walled ovoid structures with anechoic centers were present in the medulla of the right kidney. Differential diagnoses for those structures included abscess and hematoma. Echogenic swirling material was present in the urinary bladder. With the fragile skin, either a pancreatic tumor or hyperadrenocorticism were considered; therefore, the pancreas and adrenal glands were evaluated. Evaluation of the pancreas was unremarkable, and the adrenal glands were not identified. An adrenocorticotropic hormone stimulation test was also performed and was considered normal. Based on those findings, the intermittent fever was suspected to be secondary to the wounds present from the fragile skin as well as persistent pyelonephritis.
The patient was discharged with instructions to continue glargine (0.3 U/kg SC q 12 hr), amoxicillin trihydrate/clavulanate potassiuml (20 mg/kg per os q 12 hr), fluids (50 mL/kg SC q 24 hr), and potassium gluconatem (0.6 mEq/kg per os q 12 hr). Two wk after discharge, a complete blood count and serum biochemistry profile were repeated. There was resolution of the leukocytosis and left shift, persistent (but improving) anemia (hematocrit was 27%; reference range, 30–45%), persistent (but improved) hyperglycemia (14.4 mmol/L; reference range, 3.3–7.4 mmol/L), and improved azotemia (BUN was 40 mmol/L; reference range, 11.4–25 mmol/L and creatinine 133 µmol/L; reference range, 70–185 µmol/L).
The patient initially improved with treatment, the owner reporting decreased urination, weight gain, and an increased energy level. However, the patient’s condition later declined and euthanasia was performed a few months following presentation. The owner did not elect to have a necropsy performed.
Discussion
EC has been reported in humans, dogs, cats, and a cow.1,3–12,14 In veterinary medicine, EC is an uncommon type of complicated urinary tract infection characterized by accumulation of gas within the urinary bladder wall and lumen. Often associated with diabetic patients, EC has also been diagnosed in patients with primary renal glycosuria (Fanconi’s syndrome), urinary tract obstruction, chronic urinary tract infections, neurogenic bladder dysfunction, morphologic abnormalities, and immunosuppression.4,6,7,9,12 Clinical presentation is variable. In addition to signs typical of lower urinary tract infection (including hematuria and pollakiuria), pneumaturia, or air within the urine, has been reported.1
EPN is a severe necrotizing infection of the kidneys and perirenal tissues. A recent review article in the human literature found that 95% of patients diagnosed with EPN were diabetic.2 Immunosuppression, increased tissue glucose levels, and decreased renal blood flow are commonly associated with diabetes in humans and are likely to contribute to the prevalence of EPN in diabetic patients. Urinary tract obstruction is an additional risk factor for EPN in humans.2 Clinical signs are similar to other types of pyelonephritis, including fever, pyuria, and flank pain.
In addition to the dog and cat included in this case report, only one other case of EPN has been reported in the veterinary literature. That was a report of a diabetic dog that, like the two cases described herein, had concurrent EC.3 EC and EPN are most often reported as individual disease processes, and simultaneous EC and EPN is rare in both animals and humans. It has been reported that only approximately 10% of human patients with EC also had concurrent EPN.1 Although the human literature has shown female patients more likely to be affected by EC and EPN, no sex predilection has been reported in animals.1,2,11
The pathogenesis of emphysematous urinary tract infections is not completely understood. It has been suggested that the high tissue glucose levels and decreased immunity in diabetic patients can lead to infection by either glucose fermenting bacteria or yeast.13 E. coli is the most frequently isolated pathogen in humans (58% of EC cases, 70% EPN cases).1,2 E. coli is also commonly isolated in dogs and cats with EC, as well as Klebsiella spp., Proteus spp., Clostridium spp., and Aerobacter aerogenes.3,4,6,8–12 E. coli was cultured from the urine of both of the patients described in this report. Each of those patients also had an additional pathogen identified (Enterobacter and Streptococcus). Glucosuria was present in the diabetic cat reported here; however, it has been suggested that glucosuria may not be detectable in some patients with EC due to the consumption of glucose by the infective microorganisms. In nondiabetic and nonglucosuric patients, bacterial breakdown of albumin has been hypothesized to be the source of gas production.4 Interestingly, the nondiabetic patient in this case report was also hypoalbuminemic; however, the amount of proteinuria could not be adequately evaluated due to the presence of lower urinary tract inflammation. In addition, there was a history of possible hyperadrenocorticism in this dog; however, it was not receiving treatment at the time of presentation, and ultrasound examination showed both adrenal glands to be within normal limits. No specific laboratory testing for diagnosis of hyperadrenocorticism was performed at the authors’ institution. Therefore, immunosuppression due to hyperadrenocorticism cannot be completely ruled out as the underlying cause of chronic urinary tract infections and EC and EPN in this patient.
EC and EPN are imaging diagnoses. Iatrogenic causes of gas within the urinary tract (e.g., cystocentesis, previous catheterization, cystoscopy) and anatomic conditions (such as fistulas between the vagina/bowel and urinary bladder) must first be ruled out. In the absence of those conditions, detection of gas within the wall and/or lumen of the urinary bladder on ultrasound, radiographs, or computed tomography (CT) is pathognomonic for EC. With EPN, gas can be present in the renal parenchyma, collecting system, and/or perirenal tissues.
Ultrasonography can be useful for detection of early cases of emphysematous infections where only a small amount of radiographically inconspicuous gas is present.9 Ultrasonographic findings of mural EC include a hyperechoic stripe with reverberation artifact in the superficial bladder wall. Accumulation of gas immediately deep to the superficial urinary bladder mucosa with characteristic reverberation artifact is seen with luminal EC. Scanning the patient in both recumbent and standing positions can help to differentiate urinary calculi, luminal gas, and gas within the bladder wall. In both cases described in this report, gas was readily identified within the urinary tract on radiographs taken at initial presentation. It is unknown whether the decreased amount of gas detected on the follow-up ultrasound in case 1 would have been seen on radiographs because they were not repeated.
Radiographic classification of EC has been established in humans. Grade 1 is characterized by gas in the wall of the urinary bladder. Gas in the bladder wall in addition to irregularity and thickening of the bladder wall is classified as grade 2. Grade 3 is used for cases where gas is present both in the bladder wall and lumen. A grading system for use in veterinary patients has not been established.
Although emphysematous conditions of the urinary tract are commonly diagnosed with projection radiography and ultrasound, CT is the modality of choice for the diagnosis of both EC and EPN in people. CT can better define extent and severity of disease and detect mild cases as well as rule out other causes of urinary gas such as vesicocolic fistulas.15 The use of multiple grading systems based on the results of CT have been proposed for classifying the severity of EPN in humans.2,16 The use of CT for diagnosis of EC or EPN has not been reported in the veterinary literature.
The prognosis for human and veterinary patients with EC is generally favorable. Treatment involves establishing glycemic control in diabetic patients and antimicrobial therapy based on results of urine culture and sensitivity. In either severe or refractory cases, surgical debridement may be necessary. The prognosis for human patients with EPN is more guarded. Up until the late 1970s, the mortality rate in humans diagnosed with EPN was reported to be as high as 78%. Current mortality rates are still high when EPN is treated solely with medical management; however, with the evolution of improved percutaneous drainage techniques and equipment, the overall mortality rate has decreased significantly, now reported to be between 13–21%.2 Although reports of EPN in veterinary patients are limited to the two cases presented herein and one previous case, the fact that none of the affected animals had a favorable outcome suggests that the prognosis of EPN in small animals is poor when medically managed.3 This warrants the consideration of the use of more aggressive treatment options in veterinary patients with EPN.
Conclusion
EC and EPN are rare infections caused by gas-producing bacteria. These conditions affect both humans and animals and are most commonly, but not exclusively, found in diabetic patients. In addition to the two cases presented herein, only one other report of an animal with concurrent EC and EPN was found in the veterinary literature. Imaging is necessary for diagnosis and should be part of the diagnostic work up in patients with either recurrent or refractory urinary tract infections. In addition, if evidence of gas within the urinary bladder and/or kidneys is noted on either abdominal radiographs or ultrasound and previous iatrogenic causes are ruled out, the clinician should pursue additional diagnostics to evaluate for diabetes and urinary tract infection. Clinical signs and prognosis are variable; however, due to the poor outcome in the patients with concurrent EC and EPN in this and a previous veterinary report, aggressive management strategies should be recommended.
Ventrodorsal abdominal radiograph of the patient described in case 1. Gas is present within the wall and superimposed over the lumen of the urinary bladder. Gas is also evident within the left kidney (arrows). Three metallic clips are present in the right midabdomen.
Lateral abdominal radiograph of the patient described in case 2. The urinary bladder contains a large centrally located gas opacity surrounded by multiple smaller gas opacities. Multiple linear gas opacities are superimposed over the enlarged renal silhouettes.
Contributor Notes
The online version of this article (available at www.jaaha.org) contains supplementary data in the form of two videos.
R. Moon's updated credentials since article acceptance are DVM, DACVR.
R. Moon's present affiliation is with Vet-Rad, Warrensville Heights, OH.
N. Smee's present affiliation is Midwest Veterinary Imaging Associates, Inc., Shawnee, KS.
