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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2021  |  Volume : 32  |  Issue : 6  |  Page : 1646-1654
Emphysematous Pyelonephritis in Type 2 Diabetes – Clinical Profile and Management


1 Department of Surgery and Department of Urology, Lucknow, Uttar Pradesh, India
2 Department of Urology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
3 Department of Surgery and Department of Medicine, Lucknow, Uttar Pradesh, India
4 Department of Medicine, Eras Lucknow Medical College, Lucknow, Uttar Pradesh, India

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Date of Web Publication27-Jul-2022
 

   Abstract 


Emphysematous pyelonephritis (EPN) is a rare but life-threatening acute suppurative infection of the kidney among diabetics. There is no current consensus on the management of EPN. A prospective observational study was conducted at the Department of General Surgery, RML Institute of Medical Sciences, Lucknow, as well as at Eras Lucknow Medical College, Lucknow, from 2015 to 2018 to look for clinical, microbial profile and treatment outcome of diabetic patients with EPN. A total of 76 diabetic patients diagnosed with pyelonephritis were identified, of which 15 patients were diagnosed with EPN (26.3%). The mean age of the patients was 58.4 ± 6.5 years. The mean duration of diabetes was 5.3 ± 3.3 years. 12 (82%) of the 15 patients with diabetes mellitus had a glycosylated hemoglobin level higher than 7.5. Renal dysfunction at presentation was seen in 11 (73.3%) patients. Among the unilateral involvement, the left kidney was more affected. Escherichia coli in 11 (73.3%), Klebsiella sp. in one (6.6%), Pseudomonas in one (6.6%), and one each with polymicrobial and fungal urinary tract infection, respectively. Of 15 EPN patients, 13 (86.6 %) survived, and one (6.6 %) expired. Two of them underwent nephrectomy both survived. All patients with Stage I, II, and IIIa EPN (n = 12) were managed with antibiotics with or without percutaneous catheter drainage (PCD). In EPN Stage IIIb/IV (n = 3), all the three (20%) patients were managed with antibiotics and PCD, and later two (13.3%) needed nephrectomy. Only time to diagnosis, altered sensorium, shock at presentation, and thrombocytopenia were associated with poor outcome in EPN patients (P <0.05) Multiple logistic regression tests showed shock (P = 0.04) and disturbance of consciousness (P = 0.05) on (hospital admission as being the independent factors for poor outcome. EPN in diabetics needs a high index of suspicion, timely diagnosis, and good multidisciplinary approach with adequate antibiotics and surgical management for better patient outcomes.

How to cite this article:
Bhat SK, Srivastava A, Ansari N, Rai P, Singh RP, Srivastava R, Roy AK, Fatima J. Emphysematous Pyelonephritis in Type 2 Diabetes – Clinical Profile and Management. Saudi J Kidney Dis Transpl 2021;32:1646-54

How to cite this URL:
Bhat SK, Srivastava A, Ansari N, Rai P, Singh RP, Srivastava R, Roy AK, Fatima J. Emphysematous Pyelonephritis in Type 2 Diabetes – Clinical Profile and Management. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Aug 14];32:1646-54. Available from: https://www.sjkdt.org/text.asp?2021/32/6/1646/352425



   Introduction Top


Emphysematous pyelonephritis (EPN) though an uncommon infection presents as a necrotizing infection of the renal parenchyma and its surrounding areas which the potential of the presence of gas in the renal parenchyma, collecting system, or perinephric tissue.[1],[2],[3] More than 90% of all cases of EPN occur in patients with diabetes mellitus (DM)[4] more so infections remain a major cause of morbidity and mortality in patients with diabetes in developing countries,[5] which has serious implication on resources and financial burden as well. Ahlering et al,[6] Pontin et al[7] and Shokeir et al[8] observed that had concluded that meticulous resuscitative measures along with the use of appropriate medical management need to be attempted, but immediate nephrectomy should not be delayed in situations of dire emergency. There has been report of successful treatment of EPN using percutaneous catheter drainage (PCD) and antibiotic treatment has also been reported.[9] Therefore, the adequate therapeutic modalities for EPN are still controversial. The current treatment of EPN is parenteral antibiotics with percutaneous or open surgical drainage and/or nephrectomy as and when required. However, there has been no consensus regarding the management of EPN in terms of antibiotics alone or early surgical intervention to look for clinical profile and suitability of management in our population. We conducted a prospective study to appreciate the role of medical and surgical intervention when required to salvage such patients.

Our objectives in this study included (1) elucidating the clinical features, radiological classification, and prognostic factors of EPN among diabetic patients and (2) comparison of the modalities of management (i.e., antibiotic treatment alone, PCD combined with antibiotic treatment, or nephrectomy) and outcome among the various radiological classes of EPN.


   Material and Methods Top


A prospective observational study was conducted at the Department of General Surgery, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow as well as at Eras Lucknow Medical College, Lucknow, from 2015 to 2018 to look for clinical, microbial profile and treatment outcome of diabetic patients with EPN.

All diabetic patients who presented with pyelonephritis from 2015 to 2018 were prospectively followed.

The clinical features and laboratory data at the initial presentation, management, and outcomes were analyzed. Their laboratory parameter especially total leukocyte count, differential count, platelet count, serum creatinine, fasting and postprandial blood glucose, urine routine examination with cultural sensitivity, blood culture sensitivity, glycosylated hemoglobin (HbA1c), and ultrasonography of urinary tract was performed at baseline.

Contrast-enhanced computerized tomography (CECT) was performed in case of suspected renal abscess and nonrecovering pyelonephritis [Figure 1]. Computed tomography was diagnostic of pyelonephritis if single or multiple hypodense areas were evidenced after contrast medium injection along with the above-mentioned clinical features.
Figure 1 (a-c). Computerized tomography scan images of emphysematous pyelonephritis in type 2 diabetes.

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Important definitions

1. Acute pyelonephritis classically presented as a triad of fever, flank pain, and nausea or vomiting Ultrasound imaging studies were done and was considered to be suggestive of pyelonephritis if there was a combination of enlarged kidney, presence of collection and/or perinephric stranding

2. The diagnosis of EPN was made in all who met the following criteria

i. Symptoms and signs of upper urinary tract infection (UTI), or fever with a positive urine culture or pyuria without other identified infectious foci

ii. Radiological evidence by CT scan of gas accumulation in the collecting system, renal parenchyma, or perinephric or pararenal space

iii. No fistula between the urinary tract and bowel; and

iv. No recent history of trauma, urinary catheter insertion, or drainage.

The severity of EPN was graded as per the Huang classification. According to this classification, class 1 EPN is defined as gas in the collecting system only, class 2 as gas in the renal parenchyma with no extension to the extrarenal space, class 3A as an extension of gas or abscess to the perinephric space, class 3B as extension of gas or abscess to the pararenal space, and class 4 as bilateral EPN or EPN in a solitary kidney.[10]

3. Renal abscess: Clinical manifestations of renal and perinephric abscess along with imaging showing localized abscess

4. Papillary necrosis secondary to infection said to be present involving the necrosis of the renal papilla in histology along with multiple sloughed papillae that can appear in urine. Classically, the CECT depicts contrast material-filled clefts in the renal medulla, and nonenhanced lesions surrounded by rings of excreted contrast material. All patients were admitted and managed with early adequate hydration

5. Conservative treatment for EPN - Medical treatment in the form of intravenous antibiotics and percutaneous drainage

6. The success of conservative treatment - Clinical resolution and disappearance/decrease in gas on follow-up imaging during hospitalization and after discharge from hospital.

“Unsuccessful” PCD - progressive or persistent lesions on imaging studies with clinical manifestations of unstable hemodynamic or prolonged fever after management.

Acute kidney injury - AKI definition and staging according to Kidney Disease Improving Global Outcomes criteria:

Increase in serum creatinine ≥0.3 mg/dL within 48 h or increase in serum creatinine ≥1.5 times the baseline which is known or presumed to have occurred within seven days or urine volume <0.5 mL/kg/h for 6 h.

Protocol

As per the protocol followed at our department, the treatment included early adequate fluid resuscitation, prompt control of glycemic through insulin infusion, close clinical and biochemical monitoring adequate antibiotic coverage, especially a third-generation cephalosporin and a fluoroquinolone, however, those patients in septic shock were given broad spectrum of gram-positive as well as negative antibiotics and PCD (if required).

The antibiotics were revised if indicated by the results of susceptibility testing of the isolated organism.

Deterioration following this protocol especially falling general condition, new-onset shock, respiratory depression, and use of ventilatory support for a maximum of 48 h was considered for nephrectomy.

PCD - Decision of pigtail catheter insertion was based on clinical and radiological extent of disease. The presence of internal echoes in pelvicalyceal system with obstructed urinary system was immediately treated by pigtail catheter insertion. All non-responders required pigtail insertion,

Shock was defined as a systolic blood pressure <90 mm Hg.

Disturbance of consciousness included confusion, delirium, stupor, and coma. Leukocytosis was defined as a blood leukocyte count higher than 12 × 109/L.

According to the criteria of disseminated intravascular coagulation, thrombocytopenia was defined as platelet count lower than 120×109/L.

All patients were followed up for at least six months after discharge from the hospital. The study was approved by the Institutional Ethical Committee. Results are expressed as mean ± standard deviation.

The study group was divided into two groups, i.e. “Good” and “poor” outcome to look for adverse factors on outcomes.

1. Good outcome group: The patients who were successfully treated with antibiotics alone or using PCD combined with antibiotics

2. Poor outcome group: The patients who had an unsuccessful PCD followed by nephrectomy or mortality.

These two groups were compared for baseline characteristics, clinical features, and laboratory data at the initial presentation and to look for prognostic factors for poor outcomes were analyzed.


   Statistical Analysis Top


Values are expressed as mean ± standard deviation. The differences two groups were compared using Fischer exact test (two-tailed) for categorical variables and Wilcox on rank-sum test for continuous variables. Univariate analysis was used to assess the outcomes in patients with EPN. P <0.05 was taken as an upper limit of statistical significance.


   Results Top


A total of 76 diabetic patients diagnosed with pyelonephritis were identified, of which 15 patients were diagnosed with EPN (26.3%). Pyelonephritis was more common among females (60%). The subjects had a mean age of 58.4 ± 6.5 years (range 22–79 years). All the patients were type 2 diabetics with mean duration of diabetes 5.3 ± 3.3 years while one patient was diagnosed with diabetes during the diagnosis of EPN. Four (26.6 %) of DM also had diabetic retinopathy; two were background and two were proliferative. Twelve (82%) of the 15 patients with DM had an HbA1C level higher than 7.5.

Clinical features

Clinical features and laboratory data at the initial presentation are given in [Table 1]. Renal papillary necrosis and renal abscess were seen in one and two patients, respectively. The duration of symptoms prior to hospitalization ranged from 16.34 ± 7.32 (range 8–32) days. Renal dysfunction at presentation was seen in 11 (73.3%) patients. Bilateral involvement was seen in one (6.6%) patient. Among the unilateral involvement, the involved site was more frequent in the left kidney, i.e., 10 (66.6%) than in the right one (26.6%). Fever was the most common presenting symptom followed by dysuria. The prominent clinical manifestations included fever/chills (86.6%), flank pain (80%), renal angle tenderness (73.3%), vomiting (50%), and dysuria (50%). Urine and blood cultures were positive in 14 (93.3%) and three (20 %) patients respectively. The two patients had palpably enlarged kidney and one patient had crepitus in the lumbar region. Three (20%) patients had hypotension at admission and one (6.6. %) altered sensorium each. Four (26.6%) patients had had recurrent urinary infections in the past.
Table 1. Baseline clinical features and laboratory parameters (n=15).

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A total of 11 patients presented with acute kidney injury, with bilateral pyelonephritis in five of them. All presented with leukocytosis and culture positivity.

Microbiology

Gram-negative bacilli were the most frequent organisms isolated, Escherichia coli in 10 (66.6%), Klebsiella sp. in one (6.6%), Pseudomonas in one (6.6%), and one each with polymicrobial and fungal UTI respectively. The fungus included Candida albicans managed with fluconazole. Good, moderate, and poor glycemic control was seen in one (6.6%), three (20%), and 11 (73.3%), respectively.

A total of 14 patients showed urine culture positivity while three showed blood as well urine culture positivity Both. The majority of patients had urine cultures sensitive to carbapenems, tigecycline, and colistin.

Outcomes [Table 2]
Table 2. Treatment and outcomes of emphysematous pyelonephritis among diabetics.
EPN: Emphysematous pyelonephritis, PCD: Percutaneous catheter drainage.


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Of 15 EPN patients, 14 (93.3 %) survived and one (6.6 %) expired. This was a 56 years female patient who presented in septic shock, severe thrombocytopenia, and multiorgan failure was managed with inotropic support, empirical broad-spectrum antibiotics however could not survive and died within 18 h of presentation. Two of them underwent nephrectomy both survived.

All patients with Stage I, II, and IIIa EPN (n = 12) were managed with antibiotics with or without PCD. In EPN Stage IIIb/IV (n = 3), all the three (20 %) patients were managed with antibiotics and PCD, and later two (13.3%) needed nephrectomy.

Prognostic factors of mortality and poor outcome

Twelve cases were classified as having a good outcome. Three cases were classified as having a poor outcome. The comparison of baseline characteristics, clinical features, and laboratory data at the initial presentation between the good and poor outcome is given [Table 3].
Table 3. Comparison of prognostic factors for good and poor outcomes among emphysematous pyelonephritis among diabetics.

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Of different variables only time to diagnosis, altered sensorium, and shock at presentation and thrombocytopenia were associated with poor outcome in EPN patients (P <0.05).

Multiple logistic regression tests showed shock (P = 0.04) and disturbance of consciousness (P = 0.05) on hospital admission as being the independent factors for poor outcome.


   Discussion Top


All types of UTI are more frequent in patients with type 2 diabetes especially increased incidence of acute pyelonephritis observed as compared with no diabetics. Prevalence of diabetes in patients with EPN ranges from 53% to 90%, respectively. Guiard observed the association between DM and this entity.[11] Factors that increase the risk of UTIs in diabetes include age, metabolic control, diabetic nephropathy, autonomic neuropathy and vascular complications so is also true for complicated UTI, i.e., EPN in up to 90% of affected patients.[12] This was the observation in our study also where in uncontrolled metabolic status, evidences of neuropathy and nephropathy was high among our patients with EPN. Twelve (82%) of the 15 patients with DM had an HbA1C level higher than 7.5.

Pyelonephritis occurs more frequently in women than in men[13] also evident in our study wherein 60% were elderly obese diabetic females with poor glycemic control. Good, moderate, and poor glycemic control was seen in one (6.6%), three (20%), and 11 (73.3%), respectively.

Pyelonephritis in DM when bilateral is associated with greater complications. This fact is also authenticated by our observation that almost 6.6% of patients in our study had bilateral disease. A total of 11 patients (73.3%) presenting with acute kidney injury. Pyuria and leukocytosis are often reported with this entity[14] as was evident in our study also wherein 73.3% had evidence of leukocytosis suggesting bacteremia and sepsis with bacteremia evident among 20% of study group. In EPN, the left kidney is more frequently involved than the right. A meta-analysis has reported that 52% of patients had left-sided, 37.7% right-sided, and 10.2% bilateral EPN.[15] We observed a similar presentation among our study population wherein 66.6 % had leftsided involvement.

The most common offending organisms are Escherichia coli and Klebsiella followed by Proteus among patients with EPN[7] which was the observation among our study population wherein E. coli was the most common organism grown on cultures. C. albicans has been occasionally identified as a pathogen in EPN[16] was evident in one of our patients which were managed conservatively with fluconazole with good response.

The diagnosis of EPN is often delayed because the clinical manifestations are nonspecific and not different from the classic triad of upper UTI (i.e., fever, flank pain, and pyuria). Crepitus in the lumbar region is exceedingly rare, can provide an important clinical clue to the presence of EPN. Only one (6.6%) of our patients had crepitus in the lumbar region. Thus subtle clinical clues specific to this condition must arouse a high index of suspicion prompting an early CT abdomen to clinch the diagnosis and plan treatment for an infection which has a poor prognosis among those left untreated. Acute respiratory distress syndrome, disseminated intravascular coagulopathy, acute renal failure, disturbance of consciousness, and shock can reveal some severe forms.[7] Hence the time to onset to diagnosis is a critical issue in the management of these patients as evident from our study too. Those patients in our study who presented with disseminated intravascular coagulopathy, disturbance of consciousness, and shock had poor outcomes even with the best medical and surgical interventions.

Michaeli et al[1] attempted to correlate the clinical features of EPN with outcome and concluded that age, sex, site of infection, serum urea nitrogen level, and blood glucose level were not the prognostic factors, and the best combination of characteristics of EPN with favorable outcome was that of a patient with non-obstructive unilateral disease receiving combined medical and surgical treatment within a short interval of symptom onset. Our observation was that neither uncontrolled sugars nor age was associated with higher mortality rather variables such as time to diagnosis, altered sensorium, and shock at presentation, and thrombocytopenia were associated with poor outcome in EPN patients (P <0.05) while on multiple logistic regression shock (P = 0.04) and disturbance of consciousness (P = 0.05) on hospital admission were independent factors for poor outcome despite understanding that high tissue glucose levels may be a risk for EPN to develop and cause a fulminant course in patients with DM because it can provide gas-forming microbes with a microenvironment more favorable for growth and rapid catabolism, this was not evident from our study. This fallout could be because of a smaller sample size and a larger prospective study needs to be conducted for further opinion. Thus, it would be wise to intervene early among patients seen with organ systems dysfunction which usually run a more aggressive course with a worse outcome. As was evident from our patient who succumbed. An early diagnosis, aggressive and adequate medical and surgical management should be applied in these cases.

The ideal management of EPN is a still debatable and it is not clear about when to intervene surgically. However, as in case of all pyelonephritis management involves fluid and electrolyte resuscitation, antibiotics, glycemic control, and relief of obstruction if indicated. However, in case of clinical deterioration within 48 h or no improvement one may either continue medical management along with PCD or surgical nephrectomy. Despite medical therapy alone show good results in some studies.[17] However, it is observed to have high mortality as observed among others.[1] PCD along with antibiotics has been increasingly recognized over the last two decades for treating EPN.[18] Whether antibiotics along with drainage is enough, or there is a need of urgent nephrectomy? This study provides an answer to this dilemma faced by the clinicians. In the present study, majority (80%) of patients with Class I, II, or IIIa disease on CT scan improved after antibiotic therapy either alone (used in Class I only) or combined with PCD. In contrast, 50% of patients with Class IIIb disease underwent nephrectomy and improved subsequently while class 4 had 100% undergoing nephrectomy with excellent result. The results of our study support the prognostic significance of the CT scan based classification proposed by Huang and Tseng, and suggest that antibiotics along with PCD can be successfully used to manage Class I, II, IIIa EPN, whereas for IIIb and IV, a strict vigil is required as nephrectomy may have to be contemplated.

However, the number in two groups, i.e., good versus bad outcome population are low so a good statistical analysis would hold good with larger number in each thus larger studies are needed to substantiate the results.


   Conclusion Top


In our series, despite poorly controlled metabolic status high clinical suspicion, early imaging and conservative medical management among diabetics with EPN with class 1, 2, and 3a can help good outcomes while among patients belonging to class 3b and 4 needs vigilant monitoring and in case of clinical deterioration or no response nephrectomy may be mandated. EPN with thrombocytopenia, shock, and altered sensorium at presentation suggest poor prognosis require early intervention and even nephrectomy.

Conflict of interest: None declared.



 
   References Top

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Michaeli J, Mogle P, Perlberg S, Heiman S, Caine M. Emphysematous pyelonephritis. J Urol 1984;131:203-8.  Back to cited text no. 1
    
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Wan YL, Lee TY, Bullard MJ, Tsai CC. Acute gas-producing bacterial renal infection: Correlation between imaging findings and clinical outcome. Radiology 1996;198:433-8.  Back to cited text no. 2
    
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Godec CJ, Cass AS, Berkseth R. Emphysematous pyelonephritis in a solitary kidney. J Urol 1980;124:119-21.  Back to cited text no. 3
    
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Schaeffer AJ. Infections of the urinary tract. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, Campbell M, editors. Campbell’s Urology. 8th ed. Philadelphia, PA: Saunders; 2002. p. 556-8.  Back to cited text no. 4
    
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Smitherman KO, Peacock JE Jr. Infectious emergencies in patients with diabetes mellitus. Med Clin North Am 1995;79:53-77.  Back to cited text no. 5
    
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Ahlering TE, Boyd SD, Hamilton CL, Bragin SD, Chandrasoma PT, Lieskovsky G, et al. Emphysematous pyelonephritis: A 5-year experience with 13 patients. J Urol 1985;134: 1086-8.  Back to cited text no. 6
    
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Pontin AR, Barnes RD, Joffe J, Kahn D. Emphysematous pyelonephritis in diabetic patients. Br J Urol 1995;75:71-4.  Back to cited text no. 7
    
8.
Shokeir AA, El-Azab M, Mohsen T, El-Diasty T. Emphysematous pyelonephritis: A 15-year experience with 20 cases. Urology 1997 ;49: 343-6.  Back to cited text no. 8
    
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Zagoria RJ, Dyer RB, Harrison LH, Adams PL. Percutaneous management of localized emphysematous pyelonephritis. J Vasc Interv Radiol 1991;2:156-8.  Back to cited text no. 9
    
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Huang JJ, Tseng CC. Emphysematous pyelonephritis: Clinico radiological classification, management, prognosis, and pathogenesis. Arch Intern Med 2000;160:797-805.  Back to cited text no. 10
    
11.
Alasdair D, Mackie R, Drury PL. Urinary tract infection in diabetes mellitus. In: Cattell WR, editor. Infections of the Kidney and Urinary Tract. Oxford: Oxford Medical Publications; 1996. p. 219-33.  Back to cited text no. 11
    
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Hakeem L, Bhattacharyya D, Lafong C, Janjua K, Serhan J, Campbell I. Diversity and complexity of urinary tract infection in diabetes mellitus. Br J Diabetes Vasc Dis 2009;9:119-25.  Back to cited text no. 12
    
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Lipsky BA. Urinary tract infections in men. Epidemiology, pathophysiology, diagnosis, and treatment. Ann Intern Med 1989;110:138- 50.  Back to cited text no. 13
    
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Aravind C, Talwalkar NC. Renal emphysema. J Assoc of Physicians India 1997;45:739-74.  Back to cited text no. 14
    
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Aboumarzouk OM, Hughes O, Narahari K, et al. Emphysematous pyelonephritis: Time for a management plan with an evidence-based approach. Arab J Urol 2014;12:106-15.  Back to cited text no. 15
    
16.
Johnson JR, Ireton RC, Lipsky BA. Emphysematous pyelonephritis caused by Candida albicans. J Urol 1986;136:80-2.  Back to cited text no. 16
    
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Flores G, Nellen H, Magaña F, Calleja J. Acute bilateral emphysematous pyelonephritis successfully managed by medical therapy alone: A case report and review of the literature. BMC Nephrol 2002;3:4.  Back to cited text no. 17
    
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Sharma PK, Sharma R, Vijay MK, Tiwari P, Goel A, Kundu AK. Emphysematous pyelonephritis: Our experience with conservative management in 14 cases. Urol Ann 2013;5: 157-62.  Back to cited text no. 18
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Correspondence Address:
Sanjay Kumar Bhat
Department of Surgery, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.352425

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