ABSTRACT:

Emphysematous pyelonephritis (EPN) is a rapidly progressive necrotizing infection characterized by gas in the kidneys. We describe 53-year-old woman with bilateral EPN, new-onset diabetes, who despite aggressive medical management, developed septic emboli to her brain, lungs, liver and portal vein thrombosis.  Such extensive emboli have not previously been reported.

Key Words: Bilateral Emphysematous Pyelonephritis, septic emboli

INTRODUCTION:

EPN is a gas-producing, necrotizing infection involving the renal parenchyma and perirenal tissue. Female diabetics are the most commonly affected (95%). Other risk factors associated with EPN include diabetic ketoacidosis, polycycstic kidneys, renal failure, cirrhosis, alcoholism and malnutrition. As in our case, 15% of patients present without a prior history of diabetes⁽¹⁾. Mortality is between 25 to 80% but is higher in cases with bilateral kidney involvement. Diagnosis of EPN can be made by sonography, although CT scan is more specific and sensitive⁽²⁾. As our case illustrates, sonogram failed to reveal the extensive pathology that was seen on CT scan.

E. coli (69%), Klebsiella pneumonia (29%) and Proteus are most commonly isolated from the blood or urine. Presence of gas is attributed to rapid glucose fermentation by these gas producing bacteria. Previous studies ^(3,4) have shown that the most common gas is nitrogen followed by oxygen, hydrogen, and carbon dioxide. In the case presented, the patient had extensive gas and necrosis of both her kidneys and bladder with the development of emboli to multiple organs.

CASE REPORT:

A 53-year-old female without any significant past medical came to the emergency room complaining of one week of weakness, fever, generalized abdominal pain, nausea, vomiting, excessive thirst and increased frequency of urination. She became confused one day prior to admission. She was on no medications, had no history of alcohol, or drug use.

In the emergency department, the patient was conscious but confused, hypothermic (96.4 F), tachycardic (114 beats/min). Blood pressure was 130/56 mm Hg. Her cardiovascular, respiratory examinations were unremarkable. She had abdominal tenderness in left upper and lower quadrant without any guarding, rigidity or rebound tenderness. Stool was guaiac positive. She had mild pedal edema.

Her laboratory results were notable for a white blood cell count of 46,000 per mm³, with a left shift, hematocrit of 26.7%, and 308,000 platelets/mm³. Her serum blood glucose was 864 mg/dl with a bicarbonate of 20 mEq/L. The arterial blood gas was consistent with an anion gap metabolic acidosis. Her creatinine was 2.1 mg/dl. Liver function tests had a normal ALT and AST with a bilirubin of 1.8 mg/dl, and an alkaline phosphatase of 578 IU/L. Amylase was normal. Urine analysis was notable for a protein of 30 mg/dl, glucose of 1000 mg/dl, ketone of 15 mg/dl, WBC of 189/HPF and RBC of 29/HPF. Chest x-ray showed bilateral infiltrates. Abdominal x-ray showed non- specific gas pattern.

On arrival to the ICU, the patient became comatose. She was intubated for airway protection. Computed tomography (CT) scan of the brain was normal. She was started on aggressive hydration, insulin drip, ceftriaxone and levaquin for pneumonia and a urinary tract infection. Because of her elevated alkaline phosphatase an abdominal ultrasound was obtained. It showed a mass versus polyp in the gall bladder, normal kidneys without any stone or hydronephrosis.

On hospital day 2, a CT scan of the abdomen revealed inflammatory changes and air in bilateral enlarged kidneys and in the urinary bladder (Figures A1/A2).

Figure A1

Figure A2

The patient was seen by urology and underwent urgent cystoscopy, retrograde pyelography and bilateral J-J stent placement. Cystoscopy report showed inflammation and necrosis of the urinary bladder. Urine culture, sputum culture, and the cultures of the bladder tissue sent during the cystoscopy grew klebsiella pneumoniae only resistant to ampicillin. Blood cultures remained negative. An echocardiogram was negative for vegetations.

The patient remained febrile and tachycardic. On hospital day 3 she developed hypotension requiring ionotropic support with dopamine. Her mental status did not improve even off sedation.

On hospital day 4, a repeat CT scan of the brain showed multifocal areas of low attenuation in both cerebral hemispheres consistent with multiple septic emboli (Figure B).

Figure B

The next day, a CT scan of the abdomen revealed an 8-10 cm phlegmon versus developing abscess in the caudate lobe of the liver associated with right portal vein thrombosis (Figure C).

Figure C

The lungs were also visualized. Bilateral peripheral consolidations were seen at the distal bronchoalveloar bundles consistent with septic emboli (Figure D). The patient died of septic shock and renal failure on hospital day 6.

Figure D

DISCUSSION

The involvement of both kidneys is a rare complication of EPN with 31 cases reported in the literature. Management of bilateral EPN remains controversial. Review of the cases of bilateral EPN showed that 5 of 7 patients treated with nephrectomy lived^(1,5-9), while 9 of 10 cases treated medically survived^(8,10-16).  Our patient was treated with stent placement but was too unstable to be taken to surgery and died.

The pathophysiology of emphysematous pyelonephritis remains unclear.  In diabetics, it is postulated that the poor glucose control creates a fertile ground for bacteria to replicate rapidly and produce gas bubbles. Indeed, several studies have analyzed the gas content and determined that they are the result of mixed acid fermentation of glucose.  This does not explain why the kidneys should be particularly affected unless other organs do not achieve the same environment.  One article¹⁷ describes a case with similar findings of emphysematous pyelonephritis, but this time in the liver, with gas replacing the hepatic parenchyma.

In non-diabetics, emphysematous pyelonephritis is seen in patients with urinary obstruction.  Somehow bacteria trapped in a fixed small space end up producing gas that then extends to involve other areas of the kidney.

No matter what the trigger for gas formation, several articles have shown that the gas can then travel to other organs.  Chen et al⁽³⁾, used real time sonography to follow the gas bubbles produced in the kidneys. The bubbles went from the kidney to the inferior vena cava and the hepatic vein. Bhansali and Lee^(18,19) each report a case of emphysematous pyelonephritis complicated by emphysematous cholecystitis.  Sailesh⁽²⁰⁾ describes a patient with bilateral emphysematous pyelonephritis complicated by gas around the spinal cord and psoas muscle. Stein⁽⁵⁾ and Allen⁽⁷⁾ each present a case with gas dissecting into the psoas muscle.

Pathology⁽¹⁵⁾ of the removed kidney shows evidence of an acute inflammatory process with necrosis and abscess formation. In patients with EPN extending to the perinephric or pararenal spaces there is evidence of inflammation as well as microinfarctions, large infarctions, vascular thrombosis, and chronic pyelonephritis. This could imply that as the infection worsens tissue becomes infarcted.

In our case of extensive BEP no pathologic tissue was obtained. However imaging showed that within 48 hours, the liver, portal vein, and brain were all affected with evidence of emboli, tissue infarction and early abscess formation.  This has not been previously described and suggests that infected gas bubbles entered the blood stream and seeded these organs. 

REFERENCES:

1. McHugh TP, Albanna SE, Stewart NJ. Bilateral emphysematous pyelonephritis. Am J Emerg Med 1998; 16:166-169.

2. Kuo YT, Chen MT, Liu GC, Huang CN, Huang CL, Huang CH. Emphysematous pyelonephritis: imaging diagnosis and follow-up. Kaohsiung J Med Sci 1999; 15: 159-70.

3. Chen KW, Huang JJ, Wu MH, Lin XZ, Chen CY, Ruaan MK. Gas in hepatic veins: a rare and critical presentation of emphysematous pyelonephritis. J Urol 1994; 151: 125-6.

4. Yang WH, Shen NC. Gas-forming infection of the urinary tract:  an investigation of fermentation as a mechanism. Urology 1990; 5: 960-4.

5. Stein JP, Spitz A, Elmajian DA, Esrig D, Freeman JA, Grossfeld GD, et al.  Bilateral emphysematous pyelonephritis: A case report and review of the literature. Urology 1996; 47: 129-134.

6. Schenkman E, Auriemma P. Bilateral emphysematous pyelonephritis with autosomal dominant polycystic kidney disease. J Urol 1998; 159: 1633-1634.

7. Allen HA, Walsh JW, Brewer WH, Vick CW, Haynes JW. Sonography of emphysematous pyelonephritis.  J Ultrasound Med 1984; 3: 533-7.

8. George J, Chakravarthy S, John GT, Jacob CK. Bilateral emphysematous pyelonephritis responding to nonsurgical management.  Am J Nephrol 1995; 15:172-4.

9. Dennis CS, Lin GSH, Tong YC. Bilateral emphysematous pyelonephritis combined with subscapular hematoma with disseminated necrotizing fascitis.  Urol Int 2003; 70: 244-246.

10. Goyzueta JD, Katz R, Dumitrescu O, Choi HS, Kahn T.  The Disappearing Kidney. A case of emphysematous pyelonephritis. Arch Intern Med 1994; 154:2613-2615.

11. Grozel F, Berthezene Y, Guerin C, Tran-Minh VA, Croisille M.  Bilateral emphysematous pyelonephritis resolving to medical therapy: demonstration by US and CT.  Eur Radiol 1997; 7: 844-846.

12. Tahir H, Thomas G, Sheerin N, Bettington H, Pattison JM, Goldsmith DJA. Successful medical treatment of acute bilateral emphysematous pyelonephritis. Am J  Kid Dis 2000; 36: 1267-1270.

13. Flores G, Nellen H, Mangana F, Calleja J. Acute bilateral emphysematous pyelonephritis successfully managed by medical therapy alone: a case report and review of literature. BMC Nephrol 2002; 3:4.

14. Guerin C, Noel P, de Varax R,  Fournier G.  Bilateral emphysematous pyelonphritis cured by medical therapy alone. Intensive Care Med 1997; 23: 921-2.

15. Lim CS, Kim WB, Kim YS, Ahn C, Han JS, Kim S, Lee JS.  Bilateral emphysematous pyelonephritis with perirenal abscess cured by conservative therapy. J Nephrol 2000; 13: 155-158.

16. Huang JJ, Chen KW, Ruaan MK, Tsai HM. Recurrent emphysematous pyelonephritis. A case report.  Int Urol  Nephrol 1994; 26: 389-393.

17. Blachar A, Federle MP, Brancatelli G. Acute fulminant hepatic infection causing fatal “emphysematous hepatitis”: case report. Abdom Imaging 2002; 27: 188-190.

18. Bhansali A, Bhadada S, Sridhar C, Choudhary S, Khandelwal N. Concurrent emphysematous pyelonephritis and emphsematous cholecystitis in type 2 diabetes. Australas Radiol 2004; 48: 411-3.

19. Lee HM, Jeffrey RB. Emphysematous pyelonephritis with resultant emphysematous cholecystitis secondary to hematogenous dissemination. Abdom Imaging 1995; 20: 169-72.

20. Sailesh S, Randeva HS, Hillhouse EW, Patel  V. Fatal emphysematous pyelonephritis with gas in the spinal extradural space in a patient with diabetes. Diabet Med 2001; 18, 68-71.