Emphysematous Pyelonephritis: ED Presentation, Evaluation, and Management

Author: Frances Rusnack, DO, MS (EM Resident Physician, Mount Sinai Morningside/West) // Reviewed by: Summer Chavez, DO, MPH, MPM (Health Policy Fellow, Georgetown University/Medstar); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case 

A 64-year-old female with a past medical history of type 2 insulin-dependent diabetes presents to the emergency department with altered mental status. She was brought in by her spouse who reports 5 days of dysuria with worsening left-sided abdominal and flank pain, nausea, and vomiting. She has no history of abdominal surgeries or kidney stones and he denies possible trauma or accidental overdose.

Vitals: BP 102/74, HR 109, RR 16, T 39°C, SpO2 99% RA. The patient is oriented to person only with a normal neurological exam and no signs of external trauma. Lungs are clear to auscultation bilaterally, no murmurs are appreciated, and she has no visible rash. She has significant left mid abdominal and left costovertebral angle tenderness. Urinalysis is positive for leukocyte esterase, nitrites, many WBC, and large bacteria. She is found to have a lactate of 4.2 mmol/L, leukocytosis of 23 x10⁹ per L, thrombocytopenia of 50 x10⁹ per L, and an elevated creatinine to 2.9 mg/dL. CT abdomen/pelvis with IV contrast demonstrates gas in the left renal parenchyma extending to the perinephric space.

What are the next steps in management?

Background

Emphysematous pyelonephritis (EPN) is a relatively uncommon spectrum of disease characterized by gas forming bacteria causing a severe necrotizing infection of the renal parenchyma and surrounding areas.^1,2 Gas production can be local or diffuse and may spread to the perinephric spaces.^1,3

Epidemiology & Pathophysiology

EPN is a rare diagnosis. A comprehensive meta-analysis from 2013 identified a total of 628 patients.⁴ EPN often occurs in diabetic patients with an average age of 60-years old.^1,3  Females are disproportionately affected at a ratio of 3:1 which is thought to be related to increased incidence of bacteriuria.^1,4-6

The most common risk factor for the development of EPN is diabetes mellitus, type 1 and type 2.^1,4-6  Up to 90% of EPN patients have either type 1 or type 2 diabetes mellitus.³ The assumption is that elevated blood glucose levels create a favorable environment for gas forming bacteria in tissues with microvascular disease and poor perfusion.^3-5,9 Gas-forming bacteria use the glucose for fermentation, producing hydrogen peroxide and carbon dioxide gases.^3,4 Other risk factors include immunocompromised state and history of renal transplant or polycystic kidney disease. Urinary tract obstruction has been observed in up to 34% of EPN cases.⁴

The most commonly identified bacteria are enteric gram-negative facultative anaerobes such as Escherichia coli (69%) and Klebsiella pneumoniae (29%).^1,3 Other organisms found include Acinetobacter, Proteus, Streptococcus, andPseudomonas species.^5-7 Anaerobes (Bacteroides, Clostridium) and fungi (Candida, Aspergillus fumigatus) have also been associated.^1,6-8 Bacteremia occurs in up to 50% of cases and the same organisms are found in urine/pus cultures.³

Prognosis 

Mortality rates from published studies range from 11% to 42% with an average of about 25%.^3,4,14,19 Without treatment, EPN is fatal. Some factors associated with a worse prognosis include delayed diagnosis, multiple comorbidities, bilateral EPN (Class 4), Type I EPN (mortality 69%), polymicrobial infection, conservative management only, shock, altered mental status, creatinine >2.5 mg/dl, thrombocytopenia, hypoalbuminemia, and a decreased leukocyte to platelet ratio.^{1,2,4,7,9,18,19} A 2007 meta-analysis did not find an association between overall mortality and diabetes, female sex, age >50, or nephrolithiasis.¹⁹

Clinical Presentation of EPN

Patients usually present with vague complaints or symptoms typical of acute pyelonephritis such as pyuria (78%), fever (75%), abdominal or flank pain (70%), nausea, and vomiting.^1,5,6,9,19 To review the evaluation and management of pyelonephritis, please visit emDOCs: Pyelonephritis: It’s not always so straightforward…  Less common signs and symptoms include dyspnea, dysuria, pneumaturia, or crepitus.¹ The most common physical exam finding is costovertebral angle tenderness.^1,6 Because of this overlap in clinical presentation, patients may initially be treated for presumed acute pyelonephritis. An inadequate response to typical treatment may then prompt further imaging and subsequent EPN diagnosis.¹⁰ Some patients may be very ill on initial presentation with acute renal failure, dyspnea, altered mental status or other signs of septic shock.^1,5,6,9 A high index of suspicion is therefore needed in patients with EPN risk factors such as diabetes.

Differential Diagnosis 

While an uncommon diagnosis, EPN should be considered in patients who are severely ill with septic shock or who have significant risk factors such as DM, female sex, or urinary obstruction and do not respond to usual treatment for pyelonephritis. The differential diagnosis for EPN includes:

Acute pyelonephritis

Nephrolithiasis

Iatrogenic instrumentation of GU system

Xanthogranulomatous pyelonephritis

Infected nephrolithiasis

Renal abscess

Perinephric abscess

Pelvic inflammatory disease

Prostatitis

Epididymitis

Diverticulitis

Evaluation

Laboratory Studies

Findings consistent with EPN include pyuria, elevated creatinine, thrombocytopenia (46% of patients), and bacteremia.^1,3,4 Initial workup should include CBC, BMP, urinalysis, urine culture, and blood cultures.¹

Imaging Studies

CT Imaging:

While acute pyelonephritis is a clinical diagnosis, imaging should be considered in patients who appear toxic, have comorbidities, or do not respond to usual treatment.¹⁰ The diagnosis of EPN requires radiographic evidence of gas in the renal parenchyma and surrounding areas.^2,4,11 The best imaging modality is CT scan of the abdomen and pelvis with 100% detection rate.^9,4 Contrast-enhanced CT, unless contraindicated, is preferred because it allows for better visualization of the gas for staging and shows the extent of renal destruction.^1,4,11 CT will also readily detect calculi and can be used for follow up imaging to guide continued management.^1,2

CT abdomen/pelvis shows enlargement of the right kidney, heterogenous contrast enhancement and multiple parenchymal collections with gas locules. Case courtesy of <a href=”https://radiopaedia.org/”>Radiopaedia.org</a>. From the case <a href=”https://radiopaedia.org/cases/11386″>rID: 11386</a>

Abdominal X-Ray:

KUB can be useful in detecting EPN, more so in later stages of disease.¹ KUB may show air within the renal system, destruction of the renal parenchyma, loss of the psoas muscle outline, or sometimes calculi.¹ However, KUB is only accurate in 53.2% to 65% of cases.^4,14

Abdominal x-ray shows an enlarged right kidney overlying gas extending to the perinephric space. There are also paraspinal linear gas shadows indicating retroperitoneal air.  Case courtesy of Dr. Mohammad Taghi Niknejad, <ahref=”https://radiopaedia.org/”>Radiopaedia.org</a>. From the case <ahref=”https://radiopaedia.org/cases/21473”>rID: 21473</a>

Ultrasound: 

Ultrasound is a fast, inexpensive, and radiation-free imaging modality that can provide quick evidence towards the diagnosis of EPN.¹² Ultrasound may show intrarenal, intraurethral, or intracystic air artifacts seen as dirty shadowing (shadowing with irregular borders due to reflections at the gas-tissue interface) and a-lines (reverberation artifacts).^11-13Studies on POCUS in EPN are limited and it is only accurate in 69% of cases.^13,14 Additionally, POCUS is provider dependent and hindered by body habitus and nearby bowel gas.¹⁴ A follow up CT should be used to confirm and classify EPN.¹⁴

Ultrasound shows left kidney enlargement, poor corticomedullary differentiation, and linear air shadows. Case courtesy of Dr. Maulik S Patel, <a href=”https://radiopaedia.org/”>Radiopaedia.org</a>. From the case <a href=”https://radiopaedia.org/cases/17283″>rID: 17283</a>

Classification

There are two main classification systems for EPN. In 1996, Wan et al. described two types of EPN.¹⁵ In 2000, Huang and Tseng developed a more detailed classification system that coincides with treatment and is more commonly used.³

Wan et al. Classification System¹⁵

Type I: Renal parenchymal destruction with absence of fluid or presence of streaky/mottled gas

Type II: Renal or perirenal fluid with bubbly/loculated gas or presence of gas in the collecting system

Huang and Tseng Classification System³

Class 1: Gas in collecting system only

Class 2: Gas in the renal parenchyma

Class 3A: Gas or abscess extension to the perinephric space

Class 3B: Gas or abscess extension to the pararenal space beyond Gerota’s fascia

Class 4: Bilateral EPN or EPN in a solitary kidney

Treatment 

All patients should undergo general resuscitative measures with a focus on hemodynamics, glucose control, and early antibiotics.^1,14,16 Antibiotic choice should be based on local resistance patterns to cover gram-negative bacteria such as fourth-generation cephalosporins, anti-pseudomonal carbapenems, combination beta-lactamase inhibitors, fluoroquinolones, or a combination of amikacin and third-generation cephalosporins.^{7,8, 21.} Aminoglycosides should be used cautiously in those with impaired kidney function.²¹ Fluoroquinolones should be avoided in patients with risk factors for quinolone resistance such as recent hospitalization, prior quinolone use, or urinary catheter presence.²¹ Urine culture sensitivities can then be used to narrow the antibiotics that are continued for up to 6 weeks.^1,2,17

Additional treatment for EPN is controversial and urology consultants should be involved early on.¹⁹ Medical management includes antibiotics, IV fluid administration, and glucose control. When pursued alone, medical management is associated with worse outcomes and mortality rates approaching 75% in the past.^{1,19, 20} Most earlier cases therefore were treated with a combination of medical management and emergent nephrectomy or surgical drainage but there was still high mortality rate approaching 50%.²⁰ Newer strategies now include the use of percutaneous drainage (PCD) along with appropriate medical management.^3,4,14,16,17 PCD with medical management is associated with the lowest mortality (13.5%) and is often the first line treatment for patients with localized infection with functional kidney tissue such as in Class 1 and Class 2.¹⁹ Patients with renal calculi often require PCD or stent placement.^5,16,18 Emergent nephrectomy may be pursued if patients fail PCD, or have multiple risk factors, a non-functioning kidney, significant parenchymal damage, or worse classifications such as Class 3A and 3B.^1,6,14,17 The treatment for Class 4 EPN is specialized. Those with bilateral EPN should be treated based on their overall presentation as well as the condition of each individual kidney. This may include a combined approach with medical management and a single emergent nephrectomy or possible bilateral PCN, for example.¹ For solitary kidney EPN, preferred treatment is PCN combined with medical management in order to avoid lifeline renal replacement therapy. However, if the single kidney is nonfunctioning (ESRD), then emergent nephrectomy should be pursued.¹

Because of the overall high mortality and associated septic shock, many patients will require ICU level care.¹⁸

Case Resolution

The patient is septic, likely from a urinary source. She is started on piperacillin-tazobactam and IV fluids. Because of her CT findings demonstrating gas in the left renal parenchyma and extending to the perinephric space (Class 3A), urology is emergently consulted. The patient undergoes PCD and is admitted to the ICU for further management.

Key Points:

• Suspect EPN in patients with risk factors (DM, immunocompromised, female sex) who present with fever/dysuria/abdominal pain or who do not respond to usual pyelonephritis treatment.
• CT imaging of the abdomen and pelvis with contrast is the imaging modality of choice to identify gas. KUB or US may be used to aid in early recognition.
• EPN has a high mortality rate. Start resuscitation measures early including empiric antibiotic therapy such as third-generation cephalosporins with aminoglycosides, fourth-generation cephalosporins, carbapenems, combination beta-lactamase inhibitors, or fluoroquinolones depending on patient risk factors (note: take into account local antibiogram).
• Consult urology emergently to determine the need for further procedural interventions such as PCD or if severe/nonfunctioning, emergent nephrectomy.

References/Further Reading:

1. Pontin AR, Barnes RD. Current management of emphysematous pyelonephritis. Nature Reviews Urology. 2009;6(5):272-279. doi:10.1038/nrurol.2009.51
2. Deoraj S, Zakharious F, Nasim A, Missouri’s C. Emphysematous pyelonephritis: outcomes of conservative management and literature review. BMJ Case Reports. December 2018. doi:10.1136/bcr-2018-225931
3. Huang J-J, Tseng C-C. Emphysematous Pyelonephritis. Archives of Internal Medicine. 2000;160(6):797. doi:10.1001/archinte.160.6.797
4. Aboumarzouk OM, Hughes O, Narahari K, et al. Emphysematous pyelonephritis: Time for a management plan with an evidence-based approach. Arab Journal of Urology. 2014;12(2):106-115. doi:10.1016/j.aju.2013.09.005
5. Elawdy MM, Osman Y, Abouelkheir RT, El-Halwagy S, Awad B, El-Mekresh M. Emphysematous pyelonephritis treatment strategies in correlation to the CT classification: have the current experience and prognosis changed? International Urology and Nephrology. 2019;51(10):1709-1713. doi:10.1007/s11255-019-02220-3
6. Sokhal AK, Kumar M, Purkait B, et al. Emphysematous pyelonephritis: Changing trend of clinical spectrum, pathogenesis, management and outcome. Türk Üroloji Dergisi/Turkish Journal of Urology. 2017;43(2):202-209. doi:10.5152/tud.2016.14227
7. Lu Y-C, Chiang B-J, Pong Y-H, et al. Emphysematous pyelonephritis: Clinical characteristics and prognostic factors. International Journal of Urology. 2013;21(3):277-282. doi:10.1111/iju.12244
8. Shetty S. Emphysematous Pyelonephritis (EPN) Treatment & Management: Approach Considerations, Antibiotic Therapy, Percutaneous Drainage and Other Conservative Management. https://emedicine.medscape.com/article/2029011-treatment. Published December 5, 2019. Accessed May 24, 2020.
9. Mohsin N, Budruddin M, Lala S, Al-Taie S. Emphysematous Pyelonephritis: A Case Report Series of Four Patients with Review of Literature. Renal Failure. 2009;31(7):597-601. doi:10.1080/08860220903003396
10. Askew KL. Urinary Tract Infections and Hematuria. In: Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9e New York, NY: McGraw-Hill; http://accessemergencymedicine.mhmedical.com.eresources.mssm.edu/content.aspx?bookid=2353&sectionid=219643063. Accessed May 24, 2020.
11. Tonolini M. Imaging of Extrarenal Spread, Fistulising and Atypical Pyelonephritis. In: Imaging and Intervention in Urinary Tract Infections and Urosepsis. Springer International; 2018.
12. Peng C-Z, How C-K. Diagnostic Challenge of Emphysematous Pyelonephritis. The American Journal of the Medical Sciences. 2017;353(1):93. doi:10.1016/j.amjms.2016.03.002
13. Brown N, Petersen P, Kinas D, Newberry M. Emphysematous Pyelonephritis Presenting as Pneumaturia and the Use of Point-of-Care Ultrasound in the Emergency Department. Case Reports in Emergency Medicine. 2019;2019:1-5. doi:10.1155/2019/6903193
14. Somani BK, Nabi G, Thorpe P, Hussey J, Cook J, N’Dow J. Is Percutaneous Drainage the New Gold Standard in the Management of Emphysematous Pyelonephritis? Evidence from a Systematic Review. Journal of Urology. 2008;179(5):1844-1849. doi:10.1016/j.juro.2008.01.019
15. Wan YL, Lee TY, Bullard MJ and Tsai CC: Acute gas-producing bacterial renal infection: Correlation between imaging findings and clinical outcome. Radiology 1996; 198: 433.
16. Hinkamp CA, Keshvani N. Emphasising classification in emphysematous pyelonephritis. The Lancet. 2020;395(10230):1145. doi:10.1016/s0140-6736(20)30475-x
17. Turney JH. Renal conservation for gas-forming infections. The Lancet. 2000;355(9206):770-771. doi:10.1016/s0140-6736(99)00351-7
18. Elbaset M, Zahran MH, Hashem A, et al. Could platelet to leucocytic count ratio (PLR) predict sepsis and clinical outcomes in patients with emphysematous pyelonephritis? Journal of Infection and Chemotherapy. 2019;25(10):791-796. doi:10.1016/j.jiac.2019.04.008
19. Falagas ME, Alexiou VG, Giannopoulou KP, Siempos II. Risk Factors for Mortality in Patients With Emphysematous Pyelonephritis: A Meta-Analysis. Journal of Urology. 2007;178(3):880-885. doi:10.1016/j.juro.2007.05.017
20. Ubee, S.S., McGlynn, L. and Fordham, M. (2011), Emphysematous pyelonephritis. BJU International, 107: 1474-1478. doi:10.1111/j.1464-410X.2010.09660.x
21. Lu, Y., Hong, J., Chiang, B., Pong, Y., Hsueh, P., Huang, C., & Pu, Y. (2016). Recommended Initial Antimicrobial Therapy for Emphysematous Pyelonephritis. Medicine,95(21). doi:10.1097/md.0000000000003573