• Emphysematous pyelonephritis

• Conservative approach

• Contribution of CT scan

• Percutaneous drainage

Jaafar F, Abdelmoughit H, Youssef M, Fatima-Zahrae L, Amine S, et al. (2024) Emphysematous Pyelonephritis: Towards A More Conservative Approach. J Urol Res 11(2): 1148

EPN: Emphysematous Pyelonephritis; APN: Acute Pyelonephritis; AEPN: Acute Emphysematous Pyelonephritis; E. Coli: Escherichia Coli; K. Pneumoniae: Klebsiella Pneumoniae 

Emphysematous pyelonephritis (EPN) is a severe, necrotizing form of upper urinary tract infection. It is a rare but potentially lethal complication of acute pyelonephritis. Its diagnosis is clinico-biological and radiologically confirmed [1]. Computed tomography (CT) is the gold standard for confirming the diagnosis, mapping lesions and predicting prognostic factors, such as the presence of urinary obstruction [2,3].

Moreover, until the 1980s, surgical nephrectomy and/ or drainage were unavoidable, as non-surgical management was associated with a high mortality, in the order of 60-80% [4,5]. Today, with the development of new antibiotics and minimally invasive techniques, such as percutaneous or endourological drainages, the trend is to avoid surgery. The rule is a multidisciplinary conservative management combining appropriate resuscitation, targeted antibiotic therapy and drainage of urine and/or collections.

Herein, we present the experience of our department in the management of EPN based on a case series of 12 patients. We aim by this study to determine the role of CT in the diagnosis and guiding drainage procedures, and to highlight the increasingly conservative approach to the EPN.

We conducted a single-centre retrospective study of patients operated on in the department

Study design

We retrospectively report a single-center case series managed at our institution between April 2019 and January 2023. Data from both “emergency radiology” and “urology” departments was collected using the keyword “emphysematous pyelonephritis”.

To determine the prognostic and management contribution of CT scanning, we divided our population into two groups: A first group of so-called non-severe EPN, including patients classified as stages 1 and 2 of the Huang et al., classification (Table 1); and a second group of so-called severe EPN, including stages 3A, 3B and 4. Clinical, biological, radiological and management characteristics were assessed for both groups.

Study population

A total of 12 patients was selected. We included only patients that had been hospitalized and managed at our institution; had positive urine cytobacteriological examination (CBEU) for leukocyturia > 104 /mL (or > 10/mm3); had CT with evidence of emphysema in the renal parenchyma, perirenal fat and/or in the excretory tract.

We excluded patients with a recent surgery, endo-urological procedure or known urinary fistula.

Imaging protocol

All patients benefited from a CT exam using a 16 row detectors imager (General Electric Optima 640).

We routinely use

the following protocol:

· Acquisition without contrast, for looking for calculi

· Acquisitions after intravenous injection of contrast at nephrographic phase (after 90 seconds) and late phase (after 7 to 10 minutes)

Intravenous contrast injection was not allowed in 6 patients, due to severe renal insufficiency (GFR < 30 mL/min/1.73m2).

We should note that CT was conducted before cytobacteriological confirmation of urinary tract infection in 7 cases. In the remaining cases, CT was performed after the diagnosis of acute pyelonephritis.

Imaging interpretation

All files were reviewed and interpreted on the Picture Archiving and Communication System (PACS) by two senior radiologists. Native axial slices were read, with multiplanar reconstructions and windowing adjustments. Diagnostic criteria for EPN were the presence of emphysema in the upper excretory tract and/or renal parenchyma. Intra/perirenal collections were sought. Etiological evaluation focused on the search for obstructive causes of upper excretory tract dilatation, with characterization of their nature.

Each case was classified according to the prognostic classification described by Huang et al., [1] (Table 1).

All patients received empirical intravenous antibiotic therapy combining Ceftriaxone and Gentamicin. Antibiotic therapy was adapted according to the antibiogram and the clinico-biological and radiological evolution. Treatment received was also recorded: percutaneous and/or surgical drainage of collections, urine drainage, etc. Finally, evolution and survival after treatment were also noted.

All information was collected on data sheets on a Microsoft Excel form and analyzed using IBM SPSS Statistics 29. Quantitative variables were expressed as means with standard deviations. Qualitative variables were expressed as numbers of observations with percentages. Differences in means were analyzed using Student’s t-test for related variables. Categorical variables were analyzed using Fisher’s exact test. A p-value <0.05 was considered significant.

Written informed consent was obtained from the patient for participation in this study.

The ethics committee of the Faculty of Medicine of Rabat has given us its agreement. Informed consent to participate in the study was provided by the patient. The reference number is not applicable.

Clinical and biological data

Results concerning the 2 prognosis groups selected were summarized in Table 2. The majority of the population was female, accounting for 75%. Mean age was 55.7 ± 11 years. All study subjects were diabetic. The main clinical manifestations were fever/chills (75%) and signs of sepsis (tachycardia,tachypnea and hyperleukocytosis) present in all patients. However, none of the patients went into septic shock. All patients had hyperleukocytosis. Six patients had renal insufficiency, 2 of whom were in a state of acuitization of known renal insufficiency. CBEU showed pyuria in all patients and hematuria in 8.

We conducted a single-centre retrospective study of patients operated on in the department

We conducted a single-centre retrospective study of patients operated on in the department

We conducted a single-centre retrospective study of patients operated on in the department

We conducted a single-centre retrospective study of patients operated on in the department

Urine cultures were positive in 5 patients. The bacterial agents responsible were Escherichia Coli in 3 patients and Klebsiella Pneumonia in 2 others. For further bacteriological tests, blood cultures were routinely taken, and were positive in 5 patients. Cytobacteriological examination of the pus was carried out in all 4 drained patients, and was positive in one.

Radiological data

Renal involvement was unilateral in 10 patients and bilateral in 2. No patient had a single kidney or a transplanted kidney. We classified our patients according to the Huang et al. classification, with one patient in class 1, six patients in class 2, one patient in class 3A, two patients in class 3B and two patients in class 4. The mean percentage of affected parenchyma was 24.7% ± 31. Urinary obstruction was present in 7 patients, with lithiasis in 6 and cervical neoplasia with bilateral ureteral infiltration in the remaining patient.

Management

Of the 12 patients in our series, only one was managed with medical treatment alone. For the remaining patients, medical treatment was combined with percutaneous CT guided drainage in 4 patients, surgical drainage in one patient, urine drainage by double J catheter in 8 patients, and nephrectomy in one patient. Two patients underwent surgical treatment. The first patient deteriorated clinically under medical treatment and CT guided drainage, despite checking that the drain was correctly positioned. A second patient underwent delayed nephrectomy for a hypotrophic kidney with an obstructive coralliform calculus. All patients survived and were cured of their EPN .

Thus, in the severe EPN group, the patient population was younger (mean age 58.6 vs. 51.6 in the non-severe EPN group). One case of type 1 diabetes was included in the severe EPN group, while no cases were included in the non-severe EPN group. The severe EPN group was associated with a longer delay in diagnosis (15.1 days vs. 10.2 days for the non-severe EPN group). Ketoacidosis decompensation was found in all patients in the severe EPN group, compared with only 57.1% in the non-severe EPN group.) The severe EPN group included more patients known to have chronic renal failure (40% vs. 14.3% for the nonsevere EPN group), but less acute renal failure (20% vs. 33.4% for the non-severe EPN group).

Morphologically, the percentage of affected parenchyma was lower in the severe EPN group (22% vs. 25.7% in the non-severe EPN group). Urinary obstruction was less associated with severe EPN (40% vs. 71.4% for the non-severe EPN group).

In terms of management, percutaneous drainage was required in 40% of severe EPNs, compared with 28.6% of nonsevere EPNs. Surgical drainage was required in one patient with severe EPN, classified as stage 4, after failure of medical treatment and percutaneous drainage. One case of deferred nephrectomy involved a patient with a non-severe EPN on a hypotrophic kidney, with an obstructive coralliform calculus.

Acute emphysematous pyelonephritis (EPN) is a rare necrotizing infection, observed mainly in diabetic patients. This form of AENP is more frequently observed in women, with a female-to-male ratio of 3:1 [2-6]. This is in line with what we found in our series, where all our patients were diabetic and 75% were female.

Indeed, the higher incidence in women is probably linked to their greater susceptibility to urinary tract infections [4,6]. The only exception to this female predominance is in kidney transplant patients, where the incidence is similar in both men and women [4].

Unfortunately, the warning signs of EPN are non-specific, and cannot be used to differentiate EPN from uncomplicated APN. Palpation of crepitations in the lumbar region, although extremely rare, can provide an important clinical clue to the presence of EPN [2,3]. Unfortunately, this clinical sign was not sought in the observations of our series, which is linked to the retrospective nature of the study. Thus, given the absence of any specific sign, a poor response to antibiotic therapy in a diabetic patient represents the main orienting element towards EPN and should prompt the performance of an emergency abdominal CT scan (Figures 1-10) to confirm the diagnosis and plan treatment [3].

Figure 1: Axial section of an abdominal CT scan after intravenous contrast injection at portal time showing an enlarged left kidney with a nephrographic defect and surrounded by a posterior perirenal collection containing air bubbles. The appearance is compatible with class 3A EPN according to Huang et al.

Figure 2: Axial section of an abdominal CT scan without intravenous contrast injection showing air bubbles in the parenchyma and excretory tracts of the right kidney and in the excretory and perirenal tracts of the left kidney. The appearance is compatible with bilateral EPN, class 4 according to Huang et al.

Figure 3: Axial section of an abdominal CT scan without intravenous contrast injection showing a left kidney with parenchyma laminated by hydronephrosis, with air bubbles in the parenchyma and calyces. The appearance is compatible with a left EPN, class 2 according to Huang et al.

Figure 4: Axial section of an abdominal CT scan without intravenous contrast injection, showing a left kidney with parenchyma reduced by hydronephrosis, with air bubbles in the parenchyma and calyces. The appearance is compatible with a class 2 left EPN according to Huang et al.

Figure 5: Axial section of an abdominal CT scan after intravenous contrast injection at portal time, showing an enlarged right kidney with diffuse “bear’s paw” calcific dilatation upstream of a pelvic coralliform calculus, with air bubbles within the calyces and renal parenchyma. The appearance is compatible with EPN on xanthogranulomatous APN class 2 according to Huang et al.

Figure 6: Axial section of an abdominal CT scan without intravenous contrast injection showing air bubbles in the excretory tracts of both kidneys. The appearance is consistent with bilateral class 4 EPN according to Huang et al.

Figure 7: Axial section of an abdominal CT scan after intravenous contrast injection at portal time, showing an enlarged left kidney with heterogeneous parenchyma, cortico-medullary dedifferentiation and intra-parenchymal air bubbles. The appearance is compatible with a class 2 left EPN according to Huang et al.

Figure 8: Axial section of an abdominal CT scan after intravenous contrast injection at portal time showing an enlarged left kidney with heterogeneous parenchyma and intra-parenchymal, peri- and paraanterior air bubbles. The appearance is compatible with a left EPN class 3B according to Huang et al.

Figure 9: Axial section of an abdominal CT scan without intravenous contrast injection showing an enlarged right kidney, with air bubbles at the pyloric, intra-parenchymal, peri- and para-renal levels. The appearance was consistent with Huang et al. class 3B left EPN.

Figure 10: Axial sections (A, B) and coronal reconstruction (C) of an abdominal CT scan without intravenous contrast injection showing air bubbles at the pyloric, intra-parenchymal and peri-renal level of the left kidney. The appearance is compatible with a class 3A left EPN according to Huang et al

The etiopathogenic factors of EPN include the presence of gas-producing bacteria, elevated tissue glucose levels, impaired tissue perfusion and a defective immune response. Thus, the diabetic terrain combines all these factors [7-9]. Thus, high tissue glucose levels act as a substrate for microorganisms such as enterobacteria to produce hydrogen (H2 ) and carbon dioxide (CO2 ) by mixed acid fermentation of glucose. In a study by Huang et al. five out of six gas samples contained H2, and all gas samples contained CO2 [7]. In this sense, all our patients had had a long history of diabetes prior to the diagnosis of EPN, and in particular type 2 diabetes.

Other than diabetes, 50% of our patients were known to have obstructive uropathies. Reviewing the literature, we found that in the largest meta-analyses, the presence of obstructive uropathy was associated with 29-75% of EPNs [7,10-12]. However, the presence of obstructive uropathy does not appear to worsen the prognosis of patients managed for EPN [7,10,11,13].

Microbiologically, Escherichia coli is by far the most common causative organism found in EPN. It is isolated from 37 to 78% of patients; other microorganisms commonly implicated are Proteus mirabilis, Klebsiella pneumoniae, Enterococcus species and Pseudomonas aeruginosa [7,10,14]. In line with the literature, we also found that E. coli was implicated in 60% of our cases, with K. Pneumoniae as the second most frequently isolated pathogen. In a multicenter retrospective study of 570 cases by Robles-Torres et al. extended-spectrum ß-Lactamase (ESBL)-producing bacterial agents were found in 52.3% of cases, and their presence was shown to be associated with more Huang radiological classification stages 4 and thrombocytopenia, without significantly increasing mortality [10].

Several studies have investigated the factors associated with poor prognosis in EPN. Mortality was commonly associated with the presence of shock, altered consciousness, thrombocythemia, acute renal failure, hyponatremia or emergency nephrectomy [7,14-18]. The combination of these factors exponentially increases mortality [19]. On the other hand, the presence of extensive involvement, corresponding to stages 3-4 of Huang’s classification, was also considered to be a poor prognostic factor, sometimes also leading to emergency nephrectomy [14,15].

Other studies have evaluated prognostic scores [8,11,20,21]. Among these scores, the NEWS (National Early Warning Score) was the best predictor of the need for intensive care unit management and mortality [11,20,21]. According to our results, the factors associated with a high radiological stage were the presence of type 1 diabetes, chronic renal failure, delayed diagnosis, ketoacidosis decompensation, and high hyperleukocytosis. Unfortunately, due to the retrospective nature of the study, we were unable to collect data on the state of consciousness, thrombocytopenia, bilirubinemia and albuminemia for the calculation of the various scores studied, and thus to integrate them as parameters in the study.

Historically, since the first large series, Huang et al. had concluded that nephrectomy represented the best therapeutic choice and should be rapidly attempted for any extensive EPN with fulminant evolution [1]. Subsequent developments in practice have shown that emergency surgery is often poorly tolerated, due to the often-associated poor hemodynamic status [7,14,15]. Treatment of EPNs has evolved over the years, moving from invasive surgery to more conservative approaches due to the availability of better imaging modalities, more effective antibiotics and percutaneous drainage. The first therapeutic pillars of these conservative approaches are resuscitation and glycemic control measures, alongside effective antibiotic therapy [12,22-24]. Concerning antibiotic therapy, Lu et al. in their trials, demonstrated that 3rd generation cephalosporins are the antibiotic family recommended as first-line therapy for all patients. Otherwise, in cases of previous hospitalization, recent antibiotic use or disseminated intravascular coagulation, Carbapenems should be preferred. Fluoroquinolones and Gentamicin should be avoided [9].

The second pillar of conservative treatment is percutaneous drainage or urine drainage via JJ catheter/nephrostomy [12,22- 25]. In our series, percutaneous drainage was performed in 33.3% of patients, and urine drainage via JJ catheter in 66.7%. Reviewing the literature, the frequency of percutaneous drainage was relatively lower, in the range of 7.3-19%; while that of urine drainage was more variable, in the range of 25-82%.

In recent studies, emergency nephrectomy has been the exception rather than the rule [12,22,26], and failure of conservative treatment is associated with factors such as the need for emergency hemodialysis, shock on presentation, altered consciousness, severe hypoalbuminemia, inappropriate empirical antibiotic therapy and polymicrobial infection [26,27].

Our results also reflect changing trends in the management of EPN, since the efficacy of conservative treatment in our series was 91.7%. Again, for the only patient treated surgically, this required surgical drainage via lumbotomy, without recourse to nephrectomy.

CT is the reference imaging test for confirming the diagnosis, injury mapping and highlighting prognostic factors, such as the presence of urinary obstruction. The use of prognostic scores, alongside the Huang et al. classification, could provide a useful guide to patients who may require intensive care or percutaneous treatment. Treatment of EPN has evolved over the years, moving from invasive surgery to more conservative approaches due to the availability of better imaging modalities, more effective antibiotics and percutaneous drainage.

Ethical Approval

Ethics approval has been obtained to proceed with the current study.

Ethical approval for this study (Ethical Committee N°09-24) was provided by the Ethical Committee Ibn University Hospitals, Rabat Morocco on 19 January 2024.

Consent

Written informed consent was obtained from the patient for publication of this review and any accompanying images. A copy of the written consent is available for review by the Editor-inChief of this journal.

Guarantor of Submission

The corresponding author is the guarantor of submission.

Availability of Data and Materials

Supporting material is available if further analysis is needed.

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