CASE REPORTS

Emphysematous Cystitis and Pyelonephritis in a Nondiabetic Dog and a Diabetic Cat S

Rachel Moon, DVM*y, David S. Biller, DVM, DACVR, Nicole M. Smee, DVMx

ABSTRACT 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. (J Am Anim Hosp Assoc 2014; 50:124–129. DOI 10.5326/JAAHA-MS-5972)

Introduction

recumbency. According to information provided by the referring

Emphysematous cystitis (EC) and emphysematous pyelonephritis

veterinarian at the time of presentation, the patient was suspected

(EPN) are uncommon infections of the urinary tract. They are

to have hyperadrenocorticism based on an elevated cortisol level

caused by gas-producing organisms and are characterized by the

obtained 3 mo prior to referral. The dog had been treated at one

presence of gas within the urinary bladder wall, bladder lumen,

time with selegilinea, but was not receiving that medication at

renal collecting system/parenchyma, and perirenal tissues. In

the time of referral. There was also a history of recurrent urinary

humans, these infections are most often reported in diabetic

tract infections, which had been treated with, and responded to,

patients.

1,2

Slightly more than half (15 of 26) of the EC cases

antibiotics. On initial physical exam, the patient was cachectic (body

reported in the veterinary literature have occurred in animals with 3–12

To date, there is only a single

condition score of 1.5 out of 5) and dehydrated. Temperature,

known report of a veterinary patient with concurrent EC and

pulse, and respiration were within normal limits. A grade 2 out of

underlying diabetes mellitus. 3

EPN. Two additional cases of concurrent EC and EPN, one in-

6 systolic murmur was detected with the point of maximum inten-

volving a nondiabetic dog and the other a diabetic cat, are de-

sity on the left. Blood work revealed a leukocytosis with a left shift

scribed in this report.

(46.6 3 109/L; reference range, 6.0–17.0 3 109/L) with 1.9 109/L bands (reference range, 0–0.3 3 109/L), a mild hyperglycemia

Case Report

(7.2 mmol/L; reference range, 3.3–6.7 mmol/L), azotemia (blood

Case 1

urea nitrogen [BUN] was 57.3 mmol/L; reference range, 5.7–21.4

A 10 yr old spayed female miniature schnauzer weighing 4.3 kg

mmol/L and creatinine was 256 mmol/L; reference range, 44–124

presented with a 1 wk history of weakness that had progressed to

mmol/L), hypoalbuminemia (28 g/L; reference range, 30–45 g/L),

From the Veterinary Medical Teaching Hospital, College of Veterinary Medicine, Kansas State University, Manhattan, KS.

BUN blood urea nitrogen; CT computed tomography; EC emphysematous

Correspondence: [email protected] (R.M.)

cystitis; EPN emphysematous pyelonephritis; E. coli Escherichia coli; hpf high-power field; SC subcutaneous(ly) s

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.

x

N. Smee’s present affiliation is Midwest Veterinary Imaging Associates, Inc.,

Shawnee, KS.

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Concurrent Emphysematous Cystitis and Pyelonephritis

hypercholesterolemia (13.6 mmol/L; reference range, 3.2–8.7 mmol/L), and an elevated creatine kinase (28 mkat/L; reference range, 0.97–4.0 mkat/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 mkat/L; reference range, 0.2–1.3 mkat/L) and alkaline phosphatase (23 mkat/L; reference range, 0.2–2.0 mkat/L) were detected. Urinalysis, obtained by cystocentesis, revealed a urine specific gravity of 1.012, proteinuria (21 out of 31), 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

FIGURE 1 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.

II). Echogenic swirling material was present in the urinary bladder consistent with either cellular or proteinaceous debris. The

(65.5 mkat/L; reference range, 0.97–4.0 mkat/L), and a reduction

adrenal glands were within normal limits for size and un-

in phosphate (2.5 mmol/L; reference range, 0.7–2.1 mmol/L).

remarkable in shape. Numerous linear hyperechoic foci were

Alanine aminotransferase and alkaline phosphatase were persis-

present in the spleen, which were most consistent with either fi-

tently elevated. All other parameters had returned to normal.

brosis or mineralization. The liver was hyperechoic with numerous

Abdominal ultrasonography was repeated 2 days following

variably sized, poorly circumscribed, hypoechoic, and isoechoic

initial presentation. The amount of gas visualized within the

nodules. Hyperechoic foci were present in the gravity-dependent

urinary bladder wall and renal collecting systems was subjectively

portion of the gall bladder. The remainder of the ultrasound ex-

decreased. There was no change associated with the hyperechoic

amination was unremarkable. Based on blood work, urinalysis, and

foci within the renal cortices or the appearance of the liver and

imaging results a diagnosis of concurrent EC and EPN was made.

spleen.

Subsequent blood work (performed 24 hr after initial presen-

Urine culture was positive for Escherichia coli (E. coli) and

tation) revealed a mild decrease in the leukocytosis (31.3 3 109/L;

Enterobacter cloacae, both of which were found to be resistant to

reference range, 6.0–17.0 3 109/L), a reduced BUN (32 mmol/L;

enrofloxacin and ampicillin. The antibiotic therapy was changed

reference range, 5.7–21 mmol/L), an increased creatinine (327

to imipeneme (8 mg/kg IV q 8 hr) on the third day of hospital-

mmol/L; reference range, 44–124 mmol/L), a decreased albumin

ization. The patient developed anuric renal failure that was un-

(22 g/L; reference range, 30–45 g/L), an increased creatine kinase

responsive to both furosemidef and dopamineg administration

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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

FIGURE 2 Lateral abdominal radiograph of the patient de-

biochemical profile, urinalysis, and abdominal radiographs. Blood

scribed in case 2. The urinary bladder contains a large centrally

work abnormalities included leukocytosis (26.6 3 109/L; reference

located gas opacity surrounded by multiple smaller gas opacities.

range, 5.5–19.5 3 109/L) with a left shift (0.5 3 109/L; reference

Multiple linear gas opacities are superimposed over the enlarged

range, 0–0.3 3 109/L), and a normochromic normocytic anemia

renal silhouettes.

(packed cell volume was 24%; reference range, 30–45%). Serum biochemical profile showed significant hyperglycemia (31 mmol/L;

the patient returned for a follow-up examination because of an

reference range, 3.3–7.4 mmol/L), mildly elevated BUN (55

episode of vomiting and increased lethargy. A complete blood

mmol/L; reference range, 11.4–25 mmol/L), mildly elevated

count and serum biochemistry profile were repeated, which

creatinine based on the International Renal Interest Society

showed an increase in severity of hyperglycemia (40 mmol/L;

guidelines (150 mmol/L; reference range, 70–185 mmol/L), mild

reference range, 3.3–7.4 mmol/L), azotemia (BUN was 87

hyperproteinemia (90 g/L; reference range, 63–86 g/L), mild

mmol/L; reference range, 11.4–25 mmol/L and creatinine was 194

hyperphosphatemia (2.3 mmol/L; reference range, 0.9–2.1 mmol/L),

mmol/L; reference range, 70–185 mmol/L), persistent anemia

moderate hyponatremia (136 mmol/L; reference range, 150–163

(hematocrit was 23%; reference range, 30–45%), and normal

mmol/L), and mild hypochloremia (108 mmol/L; reference range,

leukocyte count (18.8 3 109/L; reference range, 5.5–19.5 3 109/L)

108–118 mmol/L). There were also multiple abnormalities found

with persistently increased band neutrophils (1.7 3 109/L; ref-

on urinalysis (obtained by cystocentesis), including a urine spe-

erence range, 0–0.3 3 109/L).

cific gravity of 1.016, glycosuria (31 out of 31), pyuria (. 100

The patient was hospitalized. Treatment included glargine

leukocytes/hpf), proteinuria (21 out of 31), hematuria (31 out

(0.6 U/kg SC q 12 hr), fluid therapy with 16 mEq potassium

of 31), and many bacilli. A urine sample was submitted for cul-

chloride/L), and ampicillin Na/sulbactam Nak (33 mg/kg IV q

ture and sensitivity.

8 hr). During that time, results of the previously submitted urine

Abdominal radiographs revealed multiple round to linear gas

culture showed abundant growth of nonhemolytic E. coli and

opacities within the mildly enlarged right and left renal silhouettes.

a-hemolytic Streptococcus spp. Both organisms were susceptible to

A well-circumscribed centrally located gas opacity measuring

the cefovecin and ampicillin Na/sulbactam Na. Over the course of

2.5 cm in diameter was present within the moderately distended

hospitalization, the hyperglycemia resolved but the patient expe-

urinary bladder with multiple small mildly indistinct gas opacities

rienced intermittent fever and multiple lacerations secondary to

surrounding it. There was mild distension of the stomach and

fragile skin syndrome.

small intestines. The colon contained a large amount of fecal material (Figure 2).

Due to the fever and fragile skin, an abdominal ultrasound was performed on the fifth day of hospitalization (10 days fol-

Based on lab work and imaging abnormalities, a diagnosis of

lowing initial presentation). Gas was not detected in either the

diabetes mellitus with concurrent EC and EPN was made. The

urinary bladder or kidneys; however, the kidneys were enlarged

patient was treated at home by the owner with glargineh [0.3 U/kg

with hyperechoic cortices, irregular margins, and decreased cor-

subcutaneously (SC) q 12 hr] and was administered one antibiotic

ticomedullary definition. Mild (i.e., 2 mm) dilation of the right

i

injection of cefovecin Na (8 mg/kg SQ). The patient was also started

renal pelvis was observed. Two well-defined, thick-walled ovoid

on a commercial prescription dietj for management of diabetes.

structures with anechoic centers were present in the medulla of the

The patient initially responded favorably to treatment with a

right kidney. Differential diagnoses for those structures included

decrease in polydipsia; however, 4 days following initial presentation,

abscess and hematoma. Echogenic swirling material was present in

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the urinary bladder. With the fragile skin, either a pancreatic tumor

In addition to the dog and cat included in this case report,

or hyperadrenocorticism were considered; therefore, the pancreas

only one other case of EPN has been reported in the veterinary

and adrenal glands were evaluated. Evaluation of the pancreas was

literature. That was a report of a diabetic dog that, like the two cases

unremarkable, and the adrenal glands were not identified. An

described herein, had concurrent EC.3 EC and EPN are most often

adrenocorticotropic hormone stimulation test was also performed

reported as individual disease processes, and simultaneous EC and

and was considered normal. Based on those findings, the inter-

EPN is rare in both animals and humans. It has been reported

mittent fever was suspected to be secondary to the wounds present

that only approximately 10% of human patients with EC also had

from the fragile skin as well as persistent pyelonephritis.

concurrent EPN.1 Although the human literature has shown fe-

The patient was discharged with instructions to continue glargine (0.3 U/kg SC q 12 hr), amoxicillin trihydrate/clavulanate

male patients more likely to be affected by EC and EPN, no sex predilection has been reported in animals.1,2,11

potassiuml (20 mg/kg per os q 12 hr), fluids (50 mL/kg SC q 24

The pathogenesis of emphysematous urinary tract infections

hr), and potassium gluconatem (0.6 mEq/kg per os q 12 hr). Two

is not completely understood. It has been suggested that the high

wk after discharge, a complete blood count and serum bio-

tissue glucose levels and decreased immunity in diabetic patients

chemistry profile were repeated. There was resolution of the

can lead to infection by either glucose fermenting bacteria or

leukocytosis and left shift, persistent (but improving) anemia

yeast.13 E. coli is the most frequently isolated pathogen in humans

(hematocrit was 27%; reference range, 30–45%), persistent (but

(58% of EC cases, 70% EPN cases).1,2 E. coli is also commonly

improved) hyperglycemia (14.4 mmol/L; reference range, 3.3–7.4

isolated in dogs and cats with EC, as well as Klebsiella spp., Proteus

mmol/L), and improved azotemia (BUN was 40 mmol/L; refer-

spp., Clostridium spp., and Aerobacter aerogenes.3,4,6,8–12 E. coli was

ence range, 11.4–25 mmol/L and creatinine 133 mmol/L; reference

cultured from the urine of both of the patients described in this

range, 70–185 mmol/L).

report. Each of those patients also had an additional pathogen

The patient initially improved with treatment, the owner

identified (Enterobacter and Streptococcus). Glucosuria was present

reporting decreased urination, weight gain, and an increased en-

in the diabetic cat reported here; however, it has been suggested

ergy level. However, the patient’s condition later declined and

that glucosuria may not be detectable in some patients with

euthanasia was performed a few months following presentation.

EC due to the consumption of glucose by the infective micro-

The owner did not elect to have a necropsy performed.

organisms. In nondiabetic and nonglucosuric patients, bacterial breakdown of albumin has been hypothesized to be the source of

Discussion

gas production.4 Interestingly, the nondiabetic patient in this case 1,3–12,14

In

report was also hypoalbuminemic; however, the amount of pro-

veterinary medicine, EC is an uncommon type of complicated

teinuria could not be adequately evaluated due to the presence

urinary tract infection characterized by accumulation of gas within

of lower urinary tract inflammation. In addition, there was a

the urinary bladder wall and lumen. Often associated with dia-

history of possible hyperadrenocorticism in this dog; however, it

betic patients, EC has also been diagnosed in patients with primary

was not receiving treatment at the time of presentation, and

renal glycosuria (Fanconi’s syndrome), urinary tract obstruction,

ultrasound examination showed both adrenal glands to be

chronic urinary tract infections, neurogenic bladder dysfunction,

within normal limits. No specific laboratory testing for diagnosis

EC has been reported in humans, dogs, cats, and a cow.

4,6,7,9,12

Clinical

of hyperadrenocorticism was performed at the authors’ institu-

presentation is variable. In addition to signs typical of lower urinary

tion. Therefore, immunosuppression due to hyperadrenocorticism

tract infection (including hematuria and pollakiuria), pneuma-

cannot be completely ruled out as the underlying cause of chronic

turia, or air within the urine, has been reported.1

urinary tract infections and EC and EPN in this patient.

morphologic abnormalities, and immunosuppression.

EPN is a severe necrotizing infection of the kidneys and

EC and EPN are imaging diagnoses. Iatrogenic causes of gas

perirenal tissues. A recent review article in the human literature

within the urinary tract (e.g., cystocentesis, previous catheteriza-

found that 95% of patients diagnosed with EPN were diabetic.2

tion, cystoscopy) and anatomic conditions (such as fistulas be-

Immunosuppression, increased tissue glucose levels, and de-

tween the vagina/bowel and urinary bladder) must first be ruled

creased renal blood flow are commonly associated with diabetes

out. In the absence of those conditions, detection of gas within the

in humans and are likely to contribute to the prevalence of EPN

wall and/or lumen of the urinary bladder on ultrasound, radio-

in diabetic patients. Urinary tract obstruction is an additional risk

graphs, or computed tomography (CT) is pathognomonic for EC.

2

factor for EPN in humans. Clinical signs are similar to other

With EPN, gas can be present in the renal parenchyma, collecting

types of pyelonephritis, including fever, pyuria, and flank pain.

system, and/or perirenal tissues.

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Ultrasonography can be useful for detection of early cases

Conclusion

of emphysematous infections where only a small amount of ra-

EC and EPN are rare infections caused by gas-producing bacteria.

diographically inconspicuous gas is present.9 Ultrasonographic

These conditions affect both humans and animals and are most

findings of mural EC include a hyperechoic stripe with rever-

commonly, but not exclusively, found in diabetic patients. In ad-

beration artifact in the superficial bladder wall. Accumulation of

dition to the two cases presented herein, only one other report of an

gas immediately deep to the superficial urinary bladder mucosa

animal with concurrent EC and EPN was found in the veterinary

with characteristic reverberation artifact is seen with luminal EC.

literature. Imaging is necessary for diagnosis and should be part of

Scanning the patient in both recumbent and standing positions

the diagnostic work up in patients with either recurrent or refractory

can help to differentiate urinary calculi, luminal gas, and gas

urinary tract infections. In addition, if evidence of gas within the

within the bladder wall. In both cases described in this report, gas

urinary bladder and/or kidneys is noted on either abdominal

was readily identified within the urinary tract on radiographs taken

radiographs or ultrasound and previous iatrogenic causes are ruled

at initial presentation. It is unknown whether the decreased amount

out, the clinician should pursue additional diagnostics to evaluate

of gas detected on the follow-up ultrasound in case 1 would have

for diabetes and urinary tract infection. Clinical signs and prognosis

been seen on radiographs because they were not repeated.

are variable; however, due to the poor outcome in the patients with

Radiographic classification of EC has been established in humans. Grade 1 is characterized by gas in the wall of the urinary

concurrent EC and EPN in this and a previous veterinary report, aggressive management strategies should be recommended.

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.

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FOOTNOTES a Anipryl; Pfizer, New York, NY b Lactated Ringer’s solution; Abbott Laboratories, North Chicago, IL c Baytril; Bayer Animal Health, Shawnee, KS d Ampicillin; Sandoz, Inc., Broomfield, CO e Imipenem; Merck and Company, Whitehouse Station, NJ f Furosemide; Vedco, Inc., St. Joseph, MO g Dopamine; American Regent, Inc., Shirley, NY h Lantus; Sanofi-aventis, Bridgewater, NJ i Convenia; Pfizer, New York, NY j Diabetic Management; Nestlé Purina PetCare Company, St. Louis, MO k Unasyn; Pfizer, New York, NY l Clavamox; Pfizer, New York, NY m Tumil-K; Virbac Animal Health, Fort Worth, TX REFERENCES 1. Thomas AA, Lane BR, Thomas AZ, et al. Emphysematous cystitis: a review of 135 cases. BJU Int 2007;100(1):17–20. 2. Ubee SS, McGlynn L, Fordham M. Emphysematous pyelonephritis. BJU Int 2011;107(9):1474–8. 3. Peli A, Fruganti A, Bettini G, et al. Emphysematous cystitis in two glycosuric dogs. Vet Res Commun 2003;27(suppl 1):419–23. 4. Lobetti RG, Goldin JP. Emphysematous cystitis and bladder trigone diverticulum in a dog. J Small Anim Pract 1998;39(3):144–7. 5. Matsuo S, Hayashi S, Watanabe T, et al. Emphysematous cystitis in a chemically-induced diabetic dog. J Toxicol Pathol 2009;22(4): 289–92. 6. Davies NL, Williams JH. Emphysematous cystitis in a non-diabetic cat. J S Afr Vet Assoc 1993;64(4):162–4. 7. Aizenberg I, Aroch I. Emphysematous cystitis due to Escherichia coli associated with prolonged chemotherapy in a non-diabetic dog. J Vet Med B Infect Dis Vet Public Health 2003;50(8):396–8. 8. Cohn LA, Cook CR, Priddy N, et al. What is your diagnosis? Emphysematous cystitis, pneumaturia and lumbar spondylosis. J Am Vet Med Assoc 2001;218(5):703–4.

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9. Petite A, Busoni V, Heinen MP, et al. Radiographic and ultrasonographic findings of emphysematous cystitis in four nondiabetic female dogs. Vet Radiol Ultrasound 2006;47(1):90–3. 10. Almondia DY, Williams J. What is your diagnosis? Emphysematous cystitis. J Am Vet Med Assoc 2010;237(2):159–60. 11. Root CR, Scott RC. Emphysematous cystitis and other radiographic manifestations of diabetes mellitus in dogs and cats. J Am Vet Med Assoc 1971;158(6):721–8. 12. Sherding RG, Chew DJ. Nondiabetic emphysematous cystitis in two dogs. J Am Vet Med Assoc 1979;174(10):1105–9.

13. Krishnasamy PV, Liby C III. Emphysematous pyelonephritis caused by Candida tropicalis. Am J Med 2010;123(4):e7–8. 14. Anderson BC. Emphysematous cystitis in a cow-an incidental lesion. Vet Med Sm Anim Clinician. 1983;78:406–8. 15. Grayson DE, Abbott RM, Levy AD, et al. Emphysematous infections of the abdomen and pelvis: a pictorial review. Radiographics 2002;22(3): 543–61. 16. Huang JJ, Tseng CC. Emphysematous pyelonephritis: clinicoradiological classification, management, prognosis, and pathogenesis. Arch Intern Med 2000;160(6):797–805.

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