Emphysematous Pyelonephritis (EPN) 

Updated: Nov 13, 2017
Author: Sugandh Shetty, MD, FRCS; Chief Editor: Edward David Kim, MD, FACS 

Overview

Practice Essentials

Emphysematous pyelonephritis (EPN) is a severe infection of the renal parenchyma that causes gas accumulation in the tissues (see the image below). EPN most often occurs in persons with diabetes mellitus, especially women. Its presentation is similar to that of acute pyelonephritis, but EPN often has a fulminating course, and can be fatal if not recognized and treated promptly.[1, 2]

Signs and symptoms

Typical presenting features of EPN include the following:

  • Fever (79%)

  • Abdominal or flank pain (71%)

  • Nausea and vomiting (17%)

  • Dyspnea (13%)

  • Acute renal impairment (35%)

  • Altered sensorium (19%)

  • Shock (29%)

Other possible findings include the following:

  • Crepitus over the flank area may occur in advanced cases of EPN

  • Pneumaturia is uncommon unless emphysematous cystitis is present

  • Subcutaneous emphysema and pneumomediastinum have been reported[3]

  • Comorbidities include alcoholism, malnourishment, renal calculi, and diabetic ketoacidosis

See Presentation for more detail.

Diagnosis

Laboratory findings include the following:

  • Leukocytosis with a left shift

  • Pyuria

  • Infected urine

  • Thrombocytopenia

  • An elevated creatinine level

  • Positive blood culture results

Computed tomography (CT) scanning is the definitive imaging test for EPN. CT may show the following:

  • Gas patterns that are streaky, streaky and mottled, or streaky and bubbly

  • Rimlike or crescent-shaped gas collections in the perinephric area

  • Gas in the renal vein or inferior vena cava and along the psoas muscle

  • Perinephric abscess may lead to significant gas accumulation in the perinephric space

  • A stone may be seen in the collecting system

Other imaging study findings are as follows:

  • Kidneys, ureter, and bladder imaging often reveals gas distribution over the region of the kidneys

  • Renal ultrasonograms often reveal high echogenic areas with dirty shadowing

Several different staging systems for EPN have been suggested. A system proposed by Michaeli et al and modified by Huang and Tseng is as follows[4] :

  • Class 1: Gas confined to the collecting system

  • Class 2: Gas confined to the renal parenchyma alone

  • Class 3A: Perinephric extension of gas or abscess

  • Class 3B: Extension of gas beyond the Gerota fascia

  • Class 4: Bilateral EPN or EPN in a solitary kidney

See Workup for more detail.

Management

Conservative treatment is indicated in the following situations:

  • Patients with compromised renal function

  • Early cases associated with gas in the collecting system alone, and patient is in otherwise stable condition

  • Class 1 and class 2 EPN

  • Class 3 and class 4 EPN: In the presence of fewer than 2 risk factors (eg, thrombocytopenia, elevated serum creatinine levels, altered sensorium, shock)

Conservative treatment consists of the following:

  • Prompt hydration

  • Fluid resuscitation

  • Systemic antibiotics

  • Relief of obstruction with percutaneous drainage or stent placement

  • Rapid control of diabetes, if present

Initial antibiotic therapy should target gram-negative bacteria and should take into account individual patient characteristics and local patterns of antibiotic resistance. In patients with renal compromise, doses must be adjusted according to creatinine clearance

Nephrectomy is indicated as follows:

  • Treatment of choice for most patients

  • No access to percutaneous drainage or internal stenting (after patient is stabilized)

  • Gas in the renal parenchyma or "dry-type" EPN

  • Possibly bilateral nephrectomy in patients with bilateral EPN

  • Class 3 and class 4 EPN: In the presence of more than 2 risk factors (eg, thrombocytopenia, elevated serum creatinine, altered sensorium, shock)

See Treatment and Medication for more detail.

For patient education resources, see Urinary Tract Infections.

Background

A case of pneumaturia was reported in 1671.[1] Kelly and MacCullum reported the first case of gas-forming renal infection in 1898.[5] Historicallly, EPN has been described by terms such as renal emphysema and pneumonephritis; Schultz and Klorfein recommended the term emphysematous pyelonephritis in 1962.[6]

The mortality rate associated with EPN was high before the advent of antibiotics. Advances in imaging technology, control of diabetes, resuscitative management, and minimally invasive treatment have improved the outcome in patients with EPN.

Until the late 1980s, emergency nephrectomy and/or open surgical drainage plus antibiotics was the accepted treatment for EPN. Since then, however, a nephron-sparing approach has gradually gained preference for less-severe cases. Percutaneous catheter drainage has demonstrated good success with low mortality, although some patients do require subsequent nephrectomy.[6]

Pathophysiology

EPN is a severe infection of the renal parenchyma that causes gas accumulation in the tissues. The infection often has a fulminating course and can be fatal if left untreated. However, urinary tract infections are common in persons with diabetes, and not all of these infections lead to EPN. The factors that predispose to EPN in persons with diabetes may include uncontrolled diabetes, high levels of glycosylated hemoglobin, and impaired host immune mechanisms.

Fermentation of glucose with carbon dioxide production by the pathogens has been proposed as the cause of gas in the tissues. Schainuck et al proposed that fermentation products from tissue necrosis produced carbon dioxide.[7] Three analyses of the gas content din EPN demonstrated that the major components include nitrogen (60%), hydrogen (15%), carbon dioxide (5%), and oxygen (8%). Huang et al concluded that mixed acid fermentation is the mechanism of gas production, based on the presence of hydrogen.[8, 9]

Although carbon dioxide is released by the bacteria, the final tissue equilibrium achieved by tissues and gas bubbles determines the final carbon dioxide content. Diabetic microangiopathy may also contribute to the slow transport of catabolic products and may lead to accumulation of gas.

Etiology

Emphysematous pyelonephritis (EPN) is typically caused by enteric gram-negative facultative anaerobes.[10] Escherichia coli is isolated in 66% of patients, and Klebsiella species are reported in 26% of patients. Proteus,Pseudomonas, and Streptococcus species are other organisms found in patients with EPN. Mixed organisms are observed in 10% of patients. Positive blood culture results are identical to urine culture results in 54% of patients.

Rarely, fungi (eg, Aspergillus fumigatus, Candida species) and protozoa (Entamoeba histolytica) have been isolated in patients with EPN.[11, 2, 12]

Epidemiology

Emphysematous pyelonephritis (EPN) is a rare condition. Only 1-2 cases per year are encountered in a typical busy urologic department in the United States. However, the frequency of reports from developing nations suggests that this may be a reflection of access to health care and health education.

The mean age of patients with EPN is reportedly 55 years, with a range of 19-81 years. The condition is 6 times more common in women. Ninety-five percent of patients have diabetes. In most patients, the diabetes is uncontrolled, with high levels of glycosylated hemoglobin (72%) or of blood sugar. Because the condition preferentially affects persons with diabetes, the reported frequency reflects how poorly diabetes is controlled in these geographical areas. Renal stones are another predisposing condition and therefore affect the frequency of EPN.

Rare cases have been reported in persons who do not have diabetes, with renal failure and immunosuppression as contributing factors. Of these patients, 22% have obstructed upper tracts, 4% have polycystic kidneys, and 4% have end-stage renal disease. Obstruction is the main cause of EPN in persons without diabetes. EPN has been reported in transplanted kidneys.[13, 14]

The left kidney is affected more commonly than the right. Bilateral cases have also been reported.

 

Prognosis

Untreated cases of emphysematous pyelonephritis (EPN) result in death. The mortality rate associated with the disease was high before the advent of antibiotics; however, advances in imaging technology, diabetes control, resuscitative management, and minimally invasive treatment have improved patient outcomes.

Huang and Tseng reported an overall EPN mortality rate of 19%.[4] They also reported significant treatment success rates with percutaneous drainage and antibiotics (66%) and with nephrectomy (90%).

Factors associated with a  poor prognosis in patients with EPN include altered level of consciousness, multiple organ failure, hyperglycemia, and leukocytosis.[15]

EPN that receives only medical treatment may lead to uncontrollable sepsis that requires surgical intervention. Perinephric abscess and renal failure are other possible complications.

 

Presentation

History and Physical Examination

Patients typically present with fever (79%), abdominal or flank pain (71%), nausea and vomiting (17%), dyspnea (13%), acute renal impairment (35%), altered sensorium (19%), shock (29%), and thrombocytopenia (46%).

Crepitus over the flank area may occur in advanced cases of EPN. Pneumaturia is uncommon unless emphysematous cystitis is present. Subcutaneous emphysema and pneumomediastinum have also been reported in a case of EPN.[3] Comorbidities include alcoholism, malnourishment, renal calculi, and diabetic ketoacidosis.

 

DDx

Diagnostic Considerations

Acute pyelonephritis also has a presentation similar to that of emphysematous pyelonephritis (EPN). Another septic condition, xanthogranulomatous pyelonephritis, which is usually associated with stones in a nonfunctioning kidney with a severe gram-negative infection, is very similar in presentation to EPN .

Xanthogranulomatous pyelonephritis may also produce gas in the renal parenchyma and perinephric space, but generally not to the degree observed with EPN. The treatment of xanthogranulomatous pyelonephritis is strictly surgical; early nephrectomy is indicated because the kidney is already nonfunctional and is not worth saving.

Differential Diagnoses

 

Workup

Approach Considerations

A high index of suspicion is important when attempting to diagnose emphysematous pyelonephritis (EPN) promptly. Recommended laboratory studies and expected results include the following:

  • Urinalysis - Pyuria, infected urine
  • Complete blood cell count with differential - Leukocytosis with a left shift, thrombocytopenia
  • Renal function tests - Elevated creatinine level
  • Blood cultures - Positive

Patients with urosepsis and shock should undergo cardiac and pulmonary function assessment as needed.

Imaging study findings that can raise suspicion of EPN include an abnormal gas shadow in the renal bed on plain radiography (kidney, ureters, bladder [KUB] view), and the presence of intrarenal gas on renal ultrasonography.[6] Computed tomography (CT) scanning is the definitive imaging test for EPN.[16, 17, 6]

Imaging Studies

Imaging studies used for diagnosis of emphysematous pyelonephritis include the following:

  • Kidney, ureter, bladder (KUB) radiographs
  • Renal ultrasonography
  • Computed tomography (CT) - The definitive technique

Patients should be stabilized with intravenous fluids and intravenous antibiotics prior to radiologic intervention. For full discussion, see Imaging in Emphysematous Pyelonephritis

Kidneys, ureter, and bladder imaging

KUB films often reveal gas distribution over the region of the kidneys, as shown in the images below. In patients with emphysematous pyelitis, the collecting system may be filled with gas. An ileus pattern may be seen, suggesting retroperitoneal inflammation.

Kidneys, ureter, and bladder imaging showing a str Kidneys, ureter, and bladder imaging showing a streaky gas pattern over the entire right kidney in a patient with emphysematous pyelonephritis.
Emphysematous pyelonephritis. Kidneys, ureter, and Emphysematous pyelonephritis. Kidneys, ureter, and bladder imaging showing gas over the region of the right kidney. White arrows outline the area. The faint outline of a staghorn calculus can be seen in the right kidney.

Ultrasonography

Renal ultrasonograms often reveal high echogenic areas with dirty shadowing. Hydronephrosis and perinephric fluid may also be seen. (See the image below.)

Emphysematous pyelonephritis. Renal sonogram showi Emphysematous pyelonephritis. Renal sonogram showing hyperechoic shadows suggestive of gas along the lower pole of the kidney.

Computed tomography

Patterns seen on CT in patients with EPN (see the images below) may include the following:

  • Streaky, streaky and mottled, or streaky and bubbly
  • Gas may be rimlike or crescent-shaped in the perinephric area
  • Gas may be seen in the renal vein or inferior vena cava (see the images below)
  • Gas may be seen along the psoas muscle
  • Perinephric abscess may lead to significant gas accumulation in the perinephric space
  • A stone may be seen in the collecting system

 

CT scan showing right renal and perinephric gas in CT scan showing right renal and perinephric gas in a patient with emphysematous pyelonephritis.
CT scan showing gas in both kidneys and the inferi CT scan showing gas in both kidneys and the inferior vena cava in a patient with bilateral emphysematous pyelonephritis.

Radiologic Classification

Over time, several groups of investigators have proposed classification systems for EPN; these are outlined below. Note that the classifications are not comparable.

In 1970, Langston and Pfister described 3 main radiographic patterns in EPN, as follows[18] :

  • Diffuse mottling of the renal parenchyma

  • Bubbly renal parenchyma surrounded by crescent-shaped gas in the perinephric space

  • Extension of gas through the Gerota fascia

In 1984, Michaeli et al suggested 3 stages of EPN, as follows[19] :

  • Stage I - Gas within the renal parenchyma or the perinephric tissue

  • Stage II - Presence of gas in the kidney and its surroundings

  • Stage III - Extension of gas through Gerota fascia or bilateral EPN

In 1996, Wan et al described 2 distinct types of EPN, as follows[20] :

  • Type I - Characterized by parenchymal destruction, with streaky or mottled parenchymal gas and an absence of fluid collection; has a fulminant course and high risk of mortality

  • Type II - Characterized by renal or perirenal fluid collection, with bubbly gas collection in the perinephric space or in the collecting system and a mortality rate of 18%; according to Wan et al, the compromised immune state of the host leads to fulminant and dry-type EPN, which is fatal

In 2000, Huang and Tseng modified the staging proposed by Michaeli et al, as follows[4] :

  • Class 1 - Gas confined to the collecting system

  • Class 2 - Gas confined to the renal parenchyma alone

  • Class 3A - Perinephric extension of gas or abscess

  • Class 3B - Extension of gas beyond the Gerota fascia

  • Class 4 - Bilateral EPN or EPN in a solitary kidney

 

Treatment

Approach Considerations

Patients with emphysematous pyelonephritis (EPN)  are extremely ill and need resuscitative measures in the intensive care unit, including oxygen, intravenous (IV) fluids, and correction of acid-base imbalances, along with glycemic control. Systolic blood pressure should be maintained above 100 mm Hg, with fluid or inotropic support if required.[6] Surgical intervention should be performed only after stabilization of the cardiorespiratory status

Prompt initiation of empiric IV antibiotic therapy is critical. The regimen chosen should be broad spectrum, primarily target gram-negative bacteria, and take into account individual patient characteristics and local patterns of antibiotic resistance.[10]

Although emergency nephrectomy has historically been the preferred treatment for EPN, a nephron-sparing approach is increasingly favored.[21, 22, 23, 24, 25, 26, 27, 28] Conservative treatment using percutaneous drainage with antibiotics is indicated as follows:

  • Patients with compromised renal function

  • Early cases associated with gas in the collecting system alone and patient is in otherwise in stable condition

  • Class 1 and class 2 EPN

  • Class 3 and class 4 EPN - In the presence of fewer than 2 risk factors (eg, thrombocytopenia, elevated serum creatinine levels, altered sensorium, shock)

Huang and Tseng reported a 66% success rate with percutaneous drainage and antibiotics in patients with EPN, while Aswathaman et al found an 80% success rate.[21] Huang and Tseng also reported a 90% success rate in patients who underwent nephrectomy. The use of nephrectomy is indicated as follows:

  • Treatment of choice for most patients

  • No access to percutaneous drainage or internal stenting (after patient is stabilized)

  • Gas in the renal parenchyma or "dry-type" EPN

  • Possibly bilateral nephrectomy in patients with bilateral EPN

  • Class 3 and class 4 EPN - In the presence of two or more risk factors (eg, thrombocytopenia, elevated serum creatinine, altered sensorium, shock)

A case report and literature review by Nana et al suggests that ureteric involvement may also be an indication for nephrectomy.[29]

The diagram below outlines the management of EPN.

Algorithm for the management of emphysematous pyel Algorithm for the management of emphysematous pyelonephritis.

Antibiotic Therapy

Optimal antibiotic therapy for emphysematous pyelonephritis (EPN) has not been fully delineated, but empiric regimens should be broad spectrum, primarily target gram-negative bacteria, and take into account individual patient characteristics and local patterns of antibiotic resistance.[10] Recommendations in the literature vary: for example, Ubee et al suggest aminogycosides, β-lactamase inhibitors, cephalosporins, and fluoroquinolones, with the selection guided by local hospital policy.[6]

A study from Taiwan by Lu et al reported high rates of resistance to ampicillin and fluoroquinolones and moderate resistance to gentamicin. These authors recommend a third-generation or fourth-generation cephalosporin (eg, ceftazidime) for initial single-agent empirical therapy in most cases, but prefer carbapenem in patients with a history of prior hospitalization and antibiotic use, need for emergency hemodialysis, or presence of disseminated intravascular coagulation, which are risk factors for resistance to third-generation cephalosporins[10] .

Overall, Lu et al recommend tailoring initial therapy according to the classification system of Huang and Tseng (see Workup/Radiologic Classification) and risk factors for resistance, as follows[10] :

  • Class 1 – A third-generation cephalosporin, with or without amikacin, plus percutaneous catheter drainage in patients with obstructive uropathy
  • Class 2, 3, and 4 without risk factors –  A third-generation cephalosporin, with or without amikacin, plus percutaneous catheter drainage
  • Class 2, 3, and 4 with risk factors – Carbapenem with or without vancomycin plus percutaneous catheter drainage

Percutaneous Drainage and Other Conservative Management

In an analysis of 48 cases, Huang and Tseng concluded that class 1 and class 2 EPN could be managed with percutaneous drainage and antibiotics.[4] This approach could also be used in patients with class 3 or 4 EPN who have fewer than two risk factors (eg, thrombocytopenia, elevated serum creatinine levels, altered sensorium, shock). However, in the presence of two or more risk factors, nephrectomy (discussed below) yielded better results. Sharma et al also experienced success with conservative management, but early diagnosis was important.[22]

Any obstruction found on imaging studies should be relieved with either percutaneous drainage or stent placement. Definitive treatment for stones should be deferred until later. The decision regarding the use of percutaneous drainage versus a double-J stent probably depends on the patient's condition.[23] Placement of a stent requires mild sedation or general anesthesia, whereas a percutaneous procedure can be performed with only a local anesthetic.

In cases of bilateral EPN or in cases of EPN in a solitary kidney, percutaneous drainage has been useful. EPN with gas in the collecting system alone or gas and fluid in the perinephric space may respond well to percutaneous drainage.

Nephrectomy

Nephrectomy is the treatment of choice in most patients with emphysematous pyelonephritis (EPN). However, patients with EPN are extremely ill and need resuscitative measures in the intensive care unit. Surgical intervention should be performed only after stabilization of the cardiorespiratory status. A retroperitoneal flank incision is the preferred approach to avoid peritoneal contamination.

Gas in the renal parenchyma or dry-type EPN should be treated immediately with nephrectomy. Bilateral nephrectomy may be necessary in patients with bilateral EPN. Mortality rates were 15-20% in 2 series in which nephrectomy was the treatment of choice in EPN, while in a study by Huang and Tseng, nephrectomy had a 10% mortality rate.[4, 24, 30]

Nephrectomy complications include injury to the colon, duodenum, and great vessels. Postoperative wound infection is common, because wound healing in these patients is compromised.

 

Medication

Medication Summary

Prompt hydration, fluid resuscitation, and systemic antibiotics are the mainstays of medical management in emphysematous pyelonephritis (EPN). Initial antibiotic therapy is based on local resistance patterns and patient factors; agents may include intravenous ampicillin, third- or fourth-generation cephalosporins, gentamicin, amikacin, vancomycin, and metronidazole. Regimens are adjusted as necessary when culture sensitivities become available. In patients with renal compromise, doses must be adjusted according to creatinine clearance.

Colloids and Crystalloids

Class Summary

Colloids (eg, IV albumin) are used to provide oncotic expansion of plasma volume. They expand plasma volume to a greater degree than isotonic crystalloids and reduce the tendency of pulmonary and cerebral edema. About 50% of the administered colloid stays intravascular.

Isotonic 0.9% sodium chloride (normal saline [NS]) and lactated Ringer (LR) are isotonic crystalloids, the standard IV fluids used for initial volume resuscitation. They expand the intravascular and interstitial fluid spaces. Typically, about 30% of administered isotonic fluid stays intravascular; therefore, large quantities may be required to maintain adequate circulating volume.

Both fluids are isotonic and have equivalent volume restorative properties. While some differences exist between metabolic changes observed with the administration of large quantities of either fluid, for practical purposes and in most situations, the differences are clinically irrelevant. No demonstrable difference in hemodynamic effect, morbidity, or mortality exists between resuscitation with either NS or LR.

Albumin IV (Albuminar, Alba)

Albumin is used for certain types of shock or impending shock. It is useful for plasma volume expansion and maintenance of cardiac output. A solution of NS and 5% albumin is available for volume resuscitation. Five percent solutions are indicated to expand plasma volume, whereas 25% solutions are indicated to raise oncotic pressure.

Antibiotics

Class Summary

Antibiotic therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Vancomycin (Vancocin)

Vancomycin is an anti-infective agent used against methicillin-sensitive S aureus (MSSA), methicillin-resistant coagulase-negative S aureus (CONS), and ampicillin-resistant enterococci in patients allergic to penicillin.

Ampicillin

Ampicillin is used for the treatment of systemic illness warranting hospitalization. It is a broad-spectrum penicillin that interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. It can be used as an alternative to amoxicillin when unable to take medication orally.

In the past, the HACEK bacteria (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) were uniformly susceptible to ampicillin. Recently, however, beta-lactamase–producing strains of HACEK have been identified.

Gentamicin

Gentamicin is used for the treatment of systemic illness warranting hospitalization. It is an aminoglycoside antibiotic for gram-negative coverage bacteria including g Pseudomonas species. It is synergistic with beta-lactamse against enterococci. This agent interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits.

Dosing regimens are numerous and are adjusted based on CrCl and changes in volume of distribution, as well as body space into which agent needs to distribute. Dose of gentamicin may be given IV/IM. Each regimen must be followed by at least trough level drawn on third or fourth dose, 0.5 h before dosing; may draw peak level 0.5 h after 30-min infusion.

Amikacin (Amikin)

Irreversibly binds to 30S subunit of bacterial ribosomes. Blocks recognition step in protein synthesis and thereby inhibits growth. Indicated for gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin.

Metronidazole (Flagyl)

Metronidazole is a nitroimidazole that, once concentrated within the organism, is reduced by intracellular electron transport proteins. The formation of free radicals causes disruption of cellular elements and subsequent death of the organism. It is the most commonly prescribed antibiotic for giardiasis. The recommended adult dose is 250 mg PO tid for 5-7 days.

Ceftazidime (Fortaz, Tazicef, Tazidime)

Third generation cephalosporin that may be considered in combination with other antibiotics. Ceftazidime arrests bacterial growth by binding to 1 or more penicillin-binding proteins, thereby, in turn, inhibiting final transpeptidation step of peptidoglycan synthesis in bacterial cell-wall synthesis and inhibiting cell-wall biosynthesis.

Cefepime (Maxipime)

Fourth-generation cephalosporin. Elicits gram-negative coverage comparable to ceftazidime, but provides better gram-positive coverage (comparable to ceftriaxone). It is a zwitterion and rapidly penetrates gram-negative cells.