Emphysematous Pyelonephritis: A Case Report Series of Four Patients with Review of Literature

Abstract

Emphysematous pyelonephritis (EPN) is an acute necrotizing infection with gas presence in the kidney, perinephric space, and/or urinary collecting system that carries a bad prognosis. Some clinical conditions predispose to this entity, such as diabetes mellitus, urinary tract obstruction, and immune-incompetence. Immediate resuscitation, broad-spectrum antibiotics, percutaneous and surgical drainage, and emergent and delayed nephrectomy are therapeutic options that should be applied in a timely fashion. We report our experience of four patients with EPN. Two of the patients were kidney transplant recipients, one patient had bilateral urolithiasis, and one patient was an elderly patient with debilitated general condition and an abdominal mass that could not be defined. Late transplant nephrectomy was performed in one patient, and three patients were treated conservatively. Three patients died, including the patient who had transplant nephrectomy. One patient who presented with lithiasis showed a remarkable recovery with conservative management. The bacteria involved were E. Coli and a resistant Klebsiella. We conclude that EPN is a life-threatening condition that carries a bad prognosis. Early diagnosis is essential for a positive outcome. Therapeutic measures should be applied immediately after diagnosis. An aggressive approach including nephrectomy may be emergently required.

Keywords:

• emphysematous pyelonephritis (EPN)
• chronic kidney disease (CKD)
• renal transplantation
• urinary tract infection
• classification

INTRODUCTION

Emphysematous pyelonephritis is a gas-producing acute necrotizing infection affecting the renal parenchyma and the perirenal area. It is caused by gas-forming uropathogens.[1] Most of the patients are diabetics. Urinary tract obstruction due to lithiasis and immunosuppression are other predisposing factors. EPN presents a medical challenge in terms of diagnosis, pathogenesis, classification, and management. While the most frequently encountered organism associated EPN is E. coli, other organisms have been reported to cause this disease, including Klebsiella, Clostridium, Candida, Aspergillus, Cryptococcus, and even amoeba.[2–6] The prognosis also varies according to the authors and situations, with a mortality of less than 20% to more than 80%.[7,8] Most experts advocate an aggressive medical and interventionist approach.[9] However, some authors report a positive outcome with a conservative management of this disease.[10,11]

CASE REPORTS

Case One

Mr. H.M. is a 57-year-old gentleman with history of hypertension (HTN) and ischemic heart disease (IHD) and chronic kidney disease (CKD). He received a first commercial kidney transplant outside the country in 2003. It was rejected and removed within the first week after transplantation. He traveled to receive a second commercial kidney transplant in July 2004. The post-operative period was again complicated with multiple problems, including extensive oral candidiasis and peri-graft collection that necessitated percutaneous drainage twice. In August 2004, he developed graft tract obstruction that required the placement of a percutaneous nephrostomy. He later developed a scrotal abscess that was drained. The serum creatinine was around 223 mmol/L, indicating moderately altered graft function. On 10/12/2007, he presented to the Royal Hospital Emergency Department with altered general condition, abdominal pain, decreased urine output, and deteriorated renal functions, with a serum creatinine of 510 mmol/L. He was septic with a white blood cells (WBC) of 31,000/cm.³ Reviewing his records revealed that a week earlier his serum creatinine was 240 mmol/L and the WBC was 37,000/cm.³ The urine culture showed Klebsiella pneumonia sensitive to meropenem. Urgent ultrasound of the graft raised the suspicion of EPN, which was confirmed by a computerized tomography. The patient was treated with fluids and intravenous antibiotics. Nevertheless, his condition deteriorated very rapidly and went into a septic shock few. Resuscitation was unsuccessful, and the patient expired.

Case Two

Mrs. S.K. was a 58-year-old woman from India. She was affected with a suboptimally controlled type 2 diabetes mellitus treated with hypoglycemic agents and bilateral renal calculi. She presented to the Royal Hospital with sepsis, fever, pain abdomen, and severe dysuria seven days in duration. Investigations showed leucocytosis, leukocyturia, deranged coagulation profile, impaired renal function, and high blood sugar at 27.1 mmol/L. Computed tomography revealed left emphysematous pyelonephritis of the native kidneys and severe hydronephrosis on the right due to pelvic-ureteral junction obstruction (see Figure 1). The urine culture showed E coli. Fluids, broad-spectrum antibiotics, and intensive insulin therapy were administered. A percutaneous nephrostomy was performed on the right side with good urine output. She improved rapidly with this management and later discharged home.

Figure 1. (A) Ultrasound of the graft showing dirty shadows in the pelvi-calycial system; (B)ultrasound of the graft in long axis.

Case Three

Mr. R.A. was an 81-years-old male with a history of diabetes and hypertension. He was admitted with sepsis and altered sensorium, with history of dysuria 5–8 days in duration. He was started on broad-spectrum antibiotics. Urine and blood cultures revealed both E. coli and Klebsiella, which were sensitive to the antibiotic. Nevertheless, and in spite of the antibiotics and supportive measures, his condition deteriorated further, and he had to be admitted to the intensive care unit. The condition remained critical thereafter. A plain x-ray of the abdomen and a computed tomography showed an EPN with gas in the upper pole of left kidney and a solid mass measuring 10 cm in the mesenteric region with a possibility of a solid malignancy or lymphoma (see Figure 2). A CT guided biopsy of the mass was performed but was not conclusive. The patient expired shortly after, most likely due to uncontrolled sepsis.

Figure 2. CT scan showing the presence of gas in the graft kidney.

Case Four

Mr. A.M. was a 55-year-old male with a history of diabetes mellitus, hypertension, and end stage renal disease. He received commercial kidney transplantation six months before presentation outside the country. He previously presented abdominal pain, altered general condition, and signs of sepsis at a local hospital. Antibiotics were administered. He was then transferred to the Royal Hospital. At this hospital, his renal functions had deteriorated, as well as his coagulation profile. There were hyperleukocytosis and thrombocytopenia. A blood culture grew Klebsiella. Computed tomography revealed extensive gas and collection in the transplanted kidney and the perinephric area involving the psoas muscle. Fluids, antibiotics, and supportive measures were instituted. He was judged initially to be unfit for surgery, and a percutaneous drainage was performed that drained only few drops of thick dark fluid, which later also grew Klebsiella. A few days later, when the condition of the patients relatively improved, he was taken for graft nephrectomy, and debridement of the affected area were performed. Graft kidney section showed multiple abscesses. A second computed tomography on the fifth post-operative day again showed presence of gas in the remainder of the psoas muscle along with huge collection (see Figure 3). He was subjected to two more debridement but his condition worsened, and he finally expired due to severe controlled sepsis.

Figure 3. CT scan showing the presence of gas in the urinary bladder.

Demographic profile and the outcome of the patients are summarized in Table 1.

Table 1 Demographic profile and outcome of our series

Patient	Age	Disease	Organism	Yao CL	Wan CL	Outcome
1	57M	RTxp, HTN, IHD	Klebsiella	II	I	Died
2	58F	DM, Bilateral Renal Calculi	Escherichia Coli	II	I	Recovered with conservative treatment.
3	81M	DM, HTN and renal mass	Klebsiella and Escherichia coli	III A	I	Died
4	55M	RTxp, DM, HTN	Klebsiella	IV	II	Died after surgical intervention

Abbreviations: CL = classification, HTN  =  hypertension, IHD =  ischemic heart disease, RTxp =  renal transplant recipient

DISCUSSION

Emphysematous pyelonephritis (EPN) is a life-threatening infective condition of the kidney and perirenal area. This is characterized by production of gas within the renal parenchyma, collecting system or the peri-nephric tissues. In 1898, Kelly et al. for the first time reported EPN in a series of patients. They described few patients suffering from gas emanating from the ureteric orifices observed during cystoscopy or bladder gaseous distension.[12,13] EPN is caused by glucose fermenting bacteria. The most common pathological agent is E. coli, which is reported to be associated in 69–90% of cases.[1] Other pathogens have also been reported, including Pseudomonas aeruginosa, bactericides,[2] Aerobacter aerogenes, Proteus mirabilis, Candida albicans,[5] Cryptococcus neoformans, Klebsiella pneumonia, Aspergillus fumigatus,[^4] Clostridium septicum,[6] and Entamoeba histolytica.[3] In our series, E. coli were isolated in two and Klebsiella in three patients.

The pathogenesis of the EPN is still not clear. Nevertheless, high-tissue concentration of glucose, defective tissue perfusion, impaired immunity, and hypoxic environment of the renal medulla, especially in diabetics with associated microvascular disease, are thought to predispose more of these patient to tissue ischemia and necrosis, potentiating the growth of the gas-forming organisms.[13]

There are many predisposing factors known to be associated with EPN. EPN occurs predominantly in diabetic patients and in patients with urinary tract obstruction. It affects females more than males, with a female to male ratio of 6:1.[14] However, in our series, three out four patients were males, and three out of four were diabetics. Two patients were renal transplant recipients. Patients with EPN usually present with fever, chills, nausea, and pain in the flanks and abdomen. Bilateral involvement of the kidneys is reported to be in only 10% of the cases.[8] Some patients will have changes in the mental status. The clinical presentation may not be very different from a severe acute pyelonephritis.[1] In the case of renal allograft involvement, there may be tenderness over the graft itself.[15] Unusual presentations have been reported and include pneumomediastinum, subcutaneous emphysema, and multiple septic emboli of the brain, liver, and the lungs.[16,17] In its severe form, EPN can ultimately lead to septic shock and multi-organ failure, with a high mortality rate. Mortality varies between 20% to more than 80%.[8,10]

The diagnosis is confirmed by radiography. The plain radiograph of the abdomen can show mottled gas in the renal and peri-renal space, but this may occur in only one-third of patients.[13] Ultrasound is an excellent means of diagnosis. It will show the presence of gas and the urinary tract obstruction. The gold standard is the computed tomography of the abdomen, as it will show the presence and the localization of the gas. It will also show the extent of the destruction of the renal parenchyma. Altered mental status, acute renal failure, thrombocytopenia, and sepsis at presentation are reported to be poor prognostic risk factors. This may explain the high mortality in our series. Dhinakar et al. from the Southern region of Oman reported two patients.[18]

The classification of the EPN is a subject of discussion. Based on 48 patients with EPN, Huang and Tseng proposed the following classification[1,19]:

• class 1: gas presence in the collecting system only (emphysematous pyelitis);

• class 2: gas presence in the renal parenchyma without extension to the extrarenal area;

• class 3A: gas and or abscess presence in the perinephric space;

• class 3B: gas or abscess presence in the pararenal area; and

• class 4: bilateral EPN of any class or EPN in a solitary kidney.

The gravity of the prognosis increases with each class, with class 4 being the worse.

According to these criteria, the patients under discussion will be classified as class 3A & 3B which carries the worse prognosis., which again may explain the high mortality.

Wan et al. proposed another radiological classification with two types[20]:

• type 1, in which there is parenchymal destruction and gas but no collection; and

• type 2, in which there is perinephric collection and gas in the collecting system.

The prognosis is much worse in type 1, with mortality of 70% versus 20% in type 2. The two classifications seem to agree on the better relative prognosis when the lesions are limited to collecting system.

The therapeutic measures for the management of EPN consist of fluid resuscitation, antibiotics, tight control of sugar, surgical or percutaneous drainage, and nephrectomy. The type and aggressiveness is guided by the degree of severity of presentation, the predisposing factor, the progress of the clinical situation, and the individual experience and preferences. Most experts advocate an aggressive medical and interventionist approach.[9] However, some authors report a positive outcome with a conservative management of this disease.[10,11] Successful medical management have been reported even in severe bilateral EPN.[4,[10],[15],21] It seems that there is no definitive rule for the choice of a conservative and or aggressive surgical approach. A crucial element is the precocity of diagnosis, for which a high suspicion index should be present as well as urgent diagnostic measures to be available and undertaken, including urgent ultrasonography and CAT. The clinical presentation will dictate the initial approach. Severe cases may require emergent drastic measures such as surgical drainage or even nephrectomy. When a conservative approach gives no or little benefit, an aggressive approach may be adopted, which may include nephrectomy.[2,[3],[5],[14],[22],23]

We conclude that EPN requires an early diagnosis and urgent treatment. The choice of the intervention depends on the gravity of the lesions and the clinical condition of the patient. Any intervention judged necessary should not be delayed. A change in the therapeutic approach may well be indicated if the progress of the patient was not satisfactory.

CONCLUSION

EPN is a severe acute necrotizing renal parenchymal infection caused by gas-forming organisms, among others. It posseses great risk and also posseses higher mortality than conventional cases of pyelonephritis. EPN has no specific signs and symptoms, and it can be present even in the absence of sepsis. EPN should be suspected in patients who are not responding to antibiotics in which there is unexplained abnormal gas formation in the body, especially in the immuno-compromised, like the diabetic with poor glycemic control and transplant recipient on immuno-suppression.

ACKNOWLEDGMENTS

The authors report no funding or support from any agency, and declare no conflict of interest.