|Year : 2016 | Volume
| Issue : 6 | Page : 722-726
Pathology of emphysematous pyelonephritis: A study of 11 cases
Archana Laxman Khade1, Shilpa K Lad2, Vinaya B Shah2
1 Department of Pathology, HBT Medical College and Dr. R. N. Cooper Hospital, Mumbai, Maharashtra, India
2 Department of Pathology, T. N. Medical College and B. Y. L. Nair Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||16-Nov-2016|
Vinaya B Shah
Flat No. 38, Building No. 2, K. K. Marg, Government Colony, Next to Race Course Haji Ali, Mumbai - 400 034, Maharashtra
Source of Support: None, Conflict of Interest: None
Objective: The objective was to study the pathological features of emphysematous pyelonephritis (EPN). Materials and Methods: A total of 11 nephrectomy specimens of EPN received in the surgical pathology section of a tertiary hospital in a metropolis city during the period 2005-2014 are included in this study. Clinical details were obtained from the patients' records. All the patients had undergone total nephrectomy. All the specimens were fixed in 10% buffered formalin and processed for paraffin wax sectioning. The sections were stained with hematoxylin and eosin stain. Results: The most common symptoms were fever and costovertebral pain. Diabetes mellitus was present in 9 out of 11 cases and one case had calculus in the pelvis. One patient had underlying diabetes which was undiagnosed during the nephrectomy. Diagnosis of EPN was confirmed by the presence of gas and fluid in the renal tissue by computed tomography. The left kidney (nine cases, 81%) was more frequently affected than the right kidney (two cases, 19%). EPN occurred in 40-60 years of age (mean age 51.5%), and out of 11 patients, 8 (81%) were female. Escherichia coli was the commonly isolated organism from urine. Eight cases were of Type II EPN and three cases were Type I EPN. Histopathologic examination of all the cases of EPN showed acute suppurative (necrotizing) inflammation of renal parenchyma and perirenal tissues associated with vasculitis of vessels and infarction. Conclusion: EPN is most commonly seen in patients with diabetes mellitus, and E. coli is the most common causative organism.
Keywords: Diabetes mellitus, emphysematous pyelonephritis, suppurative and necrotizing inflammation
|How to cite this article:|
Khade AL, Lad SK, Shah VB. Pathology of emphysematous pyelonephritis: A study of 11 cases. Med J DY Patil Univ 2016;9:722-6
| Introduction|| |
Emphysematous pyelonephritis (EPN) is a rare but life-threatening acute suppurative infection of the kidney characterized by production of gas within renal parenchyma, collecting system, or perinephric tissue. Since the first case reported by Kelly and MacCallum  in 1898, more than 180 cases of EPN have been reported in literature.  Of the cases, 60-70% are associated with uncontrolled diabetes mellitus (DM) with or without obstructive uropathy and superimposed with infection caused by gas-forming organisms.  The lack of a strict definition of this severe infection has resulted in the use of multiplicity of terms, which include renal emphysema, Pyelonephritis, pyelonephritis emphysematosa, and pneumonephrogram. The term "EPN" was recommended by Schultz and Klorfein  due to its stress on the relationship between the gas formation and acute infectious process. There are several papers in radiology , describing radiological and clinical features pertaining to EPN  with hardly any paper citing the pathologic features on EPN. Therefore, our main aim in this study was to analyze morphologic features (gross and microscopic) in 11 nephrectomy specimens of EPN with clinicopathologic correlation.
| Materials and Methods|| |
Eleven consecutive diagnosed cases of EPN in the last 10 years (2005-2014) were included in the study. Clinical details were obtained from the patients' records [Table 1]. All the patients had undergone total nephrectomy. All the specimens were fixed in 10% buffered formalin and processed for paraffin wax sectioning. The sections were stained with hematoxylin and eosin stain.
| Results|| |
The study comprised nine females (81%) and two males (19%). Nine cases were in the age group of 40-60 years and two cases were above 60 years (mean age - 51.5 years). History of diabetes was present in nine cases, out of which five patients had high blood glucose levels at the time of admission. Hematological parameters revealed high leukocyte count ranging between 18,000 and 25,000 cu mm with neutrophilia ranging between 80% and 90% in all the cases. Renal function was deranged in two cases where serum creatinine was raised to 4.2 mg/dl. Urine microscopy showed pyuria with polymorphs ranging from 30 to 40 pus cells per high-power field. One case had obstructive lesion due to calculus in the pelvis. Radiology showed the presence of air and fluid in the kidney parenchyma in all the cases. Urine culture was available in nine cases. Gram-negative microorganisms - Escherichia coli in six cases, Klebsiella Pneumoniae in two cases, and Proteus in one case were isolated.
One female patient aged 54 years had no history of diabetes clinically. Subsequent to the diagnosis of EPN on her nephrectomy specimen, she was thoroughly investigated and was found to have impaired glucose tolerance test. She was then diagnosed as diabetes and put on treatment.
Grossly, there was unilateral involvement of kidney in all our cases of EPN. Nine nephrectomy specimens were from the left kidney and two from the right kidney. The kidneys were enlarged, size ranging from 10 to 15 cm. Gross features in different cases are summarized in [Table 2]. Histopathology findings were multiple abscess cavities filled with dense acute polymorphonuclear cells, fibrinoid necrosis in the parenchyma, extending into the capsule, and perinephric fatty tissue [Figure 3]a and b. Hemorrhage was seen in the capsule of the kidney in three cases [Figure 3]c. Infarction of glomeruli and tubules was also seen along with acute polymorphonuclear cells and bacterial colonies [Figure 4]a and b. Interstitium shows dense acute inflammatory cells with edema and pus casts in the tubules and necrotizing vasculitis in the vessels showing fibrin in the vessel wall. Rest of the parenchyma which was preserved focally showed features of glomerulosclerosis; Kimmelstiel-Wilson nodules characteristic of the diabetic kidney is also seen. One case which had no history of diabetes showed fibrinoid cap, i.e., hyalinosis lesions suggesting diabetic nephropathy [Figure 5]. Based on these findings, the patient was thoroughly investigated for diabetes and found to have impaired glucose tolerance test.
Histopathological diagnosis of all cases of EPN was given as acute suppurative (necrotizing) inflammation of the renal parenchyma.
| Discussion|| |
EPN has been defined as an acute and severe necrotizing infection of parenchyma and perirenal tissue which results in the presence of gas within renal parenchyma which is best diagnosed radiologically by computed tomography (CT). Since EPN is a rare and life-threatening condition that needs an early diagnosis, treatment of choice is immediate nephrectomy.
The first case of pneumaturia was reported in 1898,  since then approximately 180 cases of EPN have been reported.  Furthermore, several terms have been used to describe the condition, such as renal emphysema, pneumonephritis, and EPN. The mortality rate associated with this condition was high before the advent of antibiotics; however, advances in imaging technology, control of diabetes, and resuscitative management have improved the outcome in patients with EPN. [Figure 1] [Figure 2]
|Figure 1: Gross of emphysematous pyelonephritis: (a) specimen of enlarged kidney with loss of cortex and medulla with adherent perirenal fatty tissue (highlighted by arrow), (b) foci of abscess within parenchyma (highlighted by arrow), (c) abscess extending toward capsule (highlighted by arrow)|
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|Figure 2: Gross of emphysematous pyelonephritis: (a) confluent abscess seen on external surface of the kidney, (b) friable necrotic parenchyma (arrow), (c and d) hemorrhagic infarct on external surface and cut surface of the kidney, (e) a pyonephrotic cavity with purulent exudate lining the cavity|
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|Figure 3: Microscopic features of emphysematous pyelonephritis (a) multiple abscess cavities of polymorphonuclear cells in parenchyma extending into perirenal fatty tissue and capsule (b) and hemorrhages in capsule (c) (H and E, ×100)|
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|Figure 4: Microscopic features of emphysematous pyelonephritis: (a) H and E section shows infarct of glomeruli and tubules surrounded by acute inflammatory exudates, necrosis, and bacterial colonies (H and E, ×100). (b) Glomerular damage and bacterial colonies, (H and E, ×400)|
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|Figure 5: Microscopy of the renal parenchyma of emphysematous pyelonephritis showing fibrinoid cap, hyalinosis lesions in the glomeruli haracteristic features of diabetic kidney. The background of acute inflammatory cells and edema seen in the interstitium. Closer view of hyalinosis lesion in the inset (H and E, ×400)|
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The clinical manifestation of EPN tends to be nonspecific, similar to clinical presentations of uncomplicated acute pyelonephritis (APN).  Nausea and vomiting (40%), abdominal pain (50%) are common symptoms. Fever is seen in over 80%. A palpable mass is rare but abdominal tenderness is common. Pyuria and leukocytosis are often reported with this entity. ,,, In our study, fever, dysuria, and abdominal discomfort/pain were noted in all the cases with palpable abdominal mass in one patient. Leukocytosis and pyuria were found in all. Urine culture report was available in nine cases only, out of which E. coli was grown in six cases. Hyperglycemia was present in five patients and raised serum creatinine was noted in two patients at the time of presentation. This disease affects women more commonly than men, as in results of the present study, presumably because of their increased susceptibility to urinary tract infection. ,
Diagnosis of EPN is difficult if it is based on the history, physical examination, and laboratory results. It requires radiological confirmation of gas within the kidney and collecting system for which abdominal radiology, intravenous pyelography, and ultrasound are done. Radiological evaluation helps often in clinching the diagnosis. Plain X-ray may reveal mottled gas shadow in the renal region. Ultrasound reveals strong focal echoes. CT plays an invaluable role in the diagnosis and management plan.
There are many classifications of EPN, mostly based on the radiological evidence that these lesions produce. Nowadays, the classification proposed by Wan et al.  and Huang and Tseng  is followed. According to Wan et al.,  EPN is categorized into two groups, Type I or Type II. Type I EPN is defined as renal necrosis with either the total absence of fluid content on CT or the presence of a streaky/mottled gas pattern demonstrated on radiograph or CT. Type II EPN was defined as either the presence of renal/perirenal fluid in association with a bubbly/loculated gas pattern or by the presence of gas in the collecting system. In our study, nine cases of EPN were of Type II and two cases of Type I.
Guiard noted the association between DM and EPN.  Several reports noted DM as an underlying disease in 80-100% cases of EPN. ,
Sometimes, it could be the presenting feature of diabetes as seen in one of our cases. A 54-year-old female had undiagnosed DM during her surgery. She was diagnosed as EPN, and at histopathological examination, there were features of diabetic kidney noted in the glomeruli (hyalinosis and Kimmelstiel-Wilson nodules). She was thoroughly investigated and was found to have impaired glucose tolerance test and diagnosed as DM and put on treatment. Most cases are associated with uncontrolled DM; however, there have been reports of nondiabetic patients with ureteral obstruction , as seen in one of our cases who was a nondiabetic. This patient had calculus in the pelvis causing obstruction.
There are several papers in radiology ,, and clinical features pertaining to EPN  with hardly any paper citing the pathologic features on EPN. Grossly and microscopically, all the cases of EPN showed enlarged kidney with confluent abscess all over the parenchyma blurring the differentiation of cortex and medulla. There are marked adhesions of capsule and perirenal fat, necrosis, breaking of tissue, infarction, and necrotizing vasculitis of vessels with extensive destruction of renal parenchyma. Among the nonneoplastic renal lesions encountered in surgical pathology section are chronic pyelonephritis, xanthogranulomatous pyelonephritis, calculous pyelonephritis, and hydronephrotic specimens. Specimens of APN are not frequently seen because the patients are treated by antibiotics and respond, especially if it is uncomplicated. These specimens are usually seen in the autopsy. The histomorphology observed in them is interstitial inflammation by polymorphs with pus casts in the tubules. There is no extensive destruction or infarction seen of renal parenchyma, which is the characteristic feature observed in all the EPN cases.
As per the definition, EPN is an acute and severe necrotizing infection of parenchyma and perirenal tissue, and also the gross and microscopic features show similar features with the destruction of parenchyma and necrotizing inflammation in the vessels and parenchyma. Hence, the morphologic (pathologic) diagnosis of EPN is acute suppurative (necrotizing) inflammation of the renal parenchyma.
Although E. coli is the most common reported pathogen, Proteus, Pseudomonas, Klebsiella, Enterobacter, Candida, and Citrobacter freundii species have been reported as the causative organism. ,,
The mechanism for gas production in EPN is not well understood. One theory is that, in uncontrolled diabetes, glucose fermentation by the offending organism provides an excellent microenvironment for the organisms growth and rapid catabolism, leading to the massive production of carbon dioxide and hydrogen. ,, Because of impaired gaseous transport, carbon dioxide and hydrogen accumulate in tissues, leading to tissue infarction and, thus, to further damage to renal parenchyma.  In cases of unrelieved urinary tract obstruction, urinary stasis leads to severe infection, and increased intrapelvicalyceal pressure compromises and impairs the renal circulation, resulting in poor tissue perfusion, which makes antibacterial therapy ineffective.
Reports on the therapeutic approaches for patients with EPN suggest that the mortality rate in patients managed medically is greater than that in patients managed surgically. ,, The combined treatment has produced a survival rate of more than 90%. ,,
| Conclusion|| |
The patients with EPN in this study were mostly diabetic, and E. coli was the commonly isolated pathogen. The most common presenting features were fever, dysuria, and flank pain. Although EPN is a rare and life-threatening condition, it should be excluded in a diabetic patient presenting as pyelonephritis as timely diagnosis, and intensive early management can decrease morbidity and mortality too. The morphologic (pathologic) diagnosis of EPN (which is a clinical terminology) is acute suppurative (necrotizing) inflammation of the renal parenchyma.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]