© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Transplant Infectious Disease, ISSN 1398-2273
Case report
Extensive emphysematous pyelonephritis in a renal allograft: case report and review of literature ~eda, D. Lorente, E. Trilla Herrera, C. Gasanz F. Agreda Castan Serrano, P. Servian Vives, I. Iztueta Saavedra, J. Morote Robles. Extensive emphysematous pyelonephritis in a renal allograft: case report and review of literature. Transpl Infect Dis 2014: 16: 642–647. All rights reserved Abstract: Emphysematous pyelonephritis (EPN) is an acute, severe necrotizing infection of the renal parenchyma and perirenal tissue, which results in the presence of gas within the renal parenchyma, collecting system, or perinephric tissue. EPN of renal allograft is rare, with only 23 cases reported in Western literature. Here, we report a patient treated successfully with surgery. We also review the literature, focusing on old and new suggested classification systems for EPN.
F. Agreda Castan~eda, D. Lorente, E. Trilla Herrera, C. Gasanz Serrano, P. Servian Vives, I. Iztueta Saavedra, J. Morote Robles Department of Urology, Vall d0 Hebron Hospital, Barcelona, Barcelona, Spain Key words: emphysematous pyelonephritis; kidney transplant; urinary tract infection; classification system; allograft nephrectomy Correspondence to: Fernando Agreda Casta~neda, Department of Urology, Vall d0 Hebron Hospital, Barcelona, Passeig de la Vall d’Hebron, 119, Barcelona 08035, Spain Tel: (+34) 622 409 780 E-mail: [email protected]
Received 16 January 2014, revised 3 March 2014, accepted for publication 9 March 2014 DOI: 10.1111/tid.12246 Transpl Infect Dis 2014: 16: 642–647
Emphysematous pyelonephritis (EPN) is an acute, severe necrotizing infection of the renal parenchyma and perirenal tissue, which results in the presence of gas within the renal parenchyma, collecting system, or perinephric tissue (1). EPN of renal allograft is rare, with only 23 cases reported in Western literature. Here, we report a patient treated successfully with surgery.
Case report A 74-year-old woman, with history of hypertension, poorly controlled insulin-dependent diabetes, and dyslipidemia, developed end-stage renal disease. She received maintenance hemodialysis from 2010 for 2 years before undergoing expanded-criteria deceased-donor kidney transplantation in March 2012. She shared 3 human leukocyte antigen identities with the kidney donor (A, B, and DR). She experienced
642
adequate allograft postoperative function and was discharged with serum creatinine level of 1.78 mg/dL. On routine follow-up visits, no complication was observed, and no hospital readmission was needed. She was on triple immunosuppression with prednisone, tacrolimus, and mycophenolate mofetil. On her last clinic visit, 1 month before admission, she had a baseline serum creatinine level of 1.3 mg/dL. One year after transplantation, she presented to her family practitioner with fever of 3 days’ duration. She could not control her blood sugar levels for 2 days (always high in rapid test machine). The patient was admitted to a third-level hospital. On arrival she was drowsy, had a temperature of 38°C, blood pressure of 90/60 mmHg, tachycardia of 110 bpm, and 10 h of anuria. Laboratory findings showed serum glucose of 715 mg/dL, urea 151 mg/dL, serum creatinine 5.34 mg/dL, sodium 121 mEq/dL, potassium 5.04 mEq/dL,
Agreda Castan~eda et al: Emphysematous pyelonephritis in renal allograft
and leukocyte count of 17000/mL with 90% neutrophils. Venous analysis showed pH of 7.3 and bicarbonate level of 9 mmol/L. Urinalysis revealed >100 red blood cells per high-power field. She was admitted to the intensive care unit and started on intravenous piperacillin-tazobactam with a provisional diagnosis of urosepsis. She underwent hemodialysis because of anuria and signs of volume overload. Within 24 h of admission, Escherichia coli grew in urine and blood cultures. Computed tomography (CT) of the abdomen revealed an EPN of the renal allograft, with >50% of the renal parenchyma involved and no dilatation of collecting system, classified as Stage 3 (Al-Geizawi et al. [2], Fig. 1). The patient was then transferred to the renal transplant team, and a renal allograft nephrectomy was performed, 48 h after initial admission. After surgery and for 48 h, the patient was under noradrenalin treatment and started hemodialysis through a jugular venous catheter. Two weeks after surgery, she had a fever episode. A CT scan was performed, and showed a liquid collection of 6 cm, which was successfully drained percutaneously. Three weeks after admission, the patient was discharged, on a maintenance hemodialysis program. To the date of this report, no further complications were observed and the patient is back on the deceaseddonor kidney transplantation waiting list.
a risk factor for EPN, and women are more commonly affected than men in a ratio of 4:1. Gas-forming organisms, especially E. coli, and then Klebsiella pneumoniae, are most commonly seen in EPN. It is believed that with severe infection, areas of ischemic injury develop. The presence of necrotic tissue with high glucose concentration provides the ideal environment for such organisms to ferment glucose to lactose, carbon dioxide, and hydrogen, resulting in the clinical entity known as EPN (3). The clinical presentation of EPN is usually that of severe pyelonephritis that rapidly progresses to sepsis with multiple organ failure. Although evidence of EPN can be seen on plain radiographs and ultrasound, the gold standard for the diagnosis and staging of EPN is CT scanning (4). EPN classifications usually have been based on imaging. The first classification used plain abdominal x-rays (5), but the newer systems are based in CT scanning. The most commonly used, in this decade, is the Huang and Tseng classification (4) (Table 1). Unfortunately, no cases of EPN after kidney transplantation were included in their series. Consequently, this staging system is not really applicable to the management of EPN in transplanted kidneys, because all cases of EPN in renal allografts would be categorized as Stage 4. EPN classification according to Huang and Tseng (3)
Discussion EPN is a necrotizing infection of the kidney and its surroundings, defined by the presence of gas in the renal parenchyma, collecting system, or perinephric space (1). EPN is most commonly encountered in diabetics, with >80% of reported cases occurring in diabetic patients (3). Urinary tract obstruction is clearly
1
Gas in collecting system only
2
Parenchymal gas only
3A
Extension of gas into perinephric space
3B
Extension of gas into pararenal space
4
EPN in solitary kidney or bilateral disease
EPN, emphysematous pyelonephritis.
Table 1
EPN of renal allograft according to Al-Geizawi et al. (2)
Fig. 1. Renal allograft in right iliac fossa (circle). Parenchymal involvement is almost 90%, Al-Geizawi Stage 3 (2).
Stage 1
Gas in the collecting system
Stage 2
Gas replacing 50% of renal parenchyma; or extensive spread of infection in the perinephric area; or patient with evidence of multiple organ failure, uncontrolled sepsis, or shock not responding to medical management
EPN, emphysematous pyelonephritis.
Table 2
Transplant Infectious Disease 2014: 16: 642–647
643
644
Transplant Infectious Disease 2014: 16: 642–647
Table 3
et al. (17)
Iqubal
et al. (16)
Cheng
Stone (15)
Goral and
et al. (14)
Akalin
et al. (13)
Kalra
et al. (12)
Glen
et al. (11)
O’Donnell
et al. (10)
Potter
et al. (10)
Potter
et al. (9)
Balsara
et al. (8)
Brenbridge
and Feest (7)
Parameswaran
Author (ref)
38, F
55, M
55, F
62, M
35, M
66, F
27, M
39, M
31, F
32, M
33, M
53, F
gender
years,
Age in
2 years
7 years
dialysis)
months on
(last 8
5.5 years
5 years
3 months
NA
5 years
5 weeks
20 months
6 weeks
2 weeks
7 weeks
transplant
Time after
No
No
No
No
NA
NA
NA
No
No
No
No
No
obstruction
Urinary
azathioprine, prednisolone
DM
Cyclosporine,
prednisone
Cyclosporine,
immunosuppression
Not on
prednisolone
azathioprine,
Cyclosporine,
NA
NA
NA
NA
NA
prednisone
Cyclosporine,
prednisone
Azathioprine,
prednisone
Azathioprine,
Immunosuppression
transplant
Post-
DM
transplant
Post-
Type 1
Type 1
No
Yes
Yes
Type 1
Type 1
DM
transplant
Post-
DM
transplant
Post-
DM
transplant
Post-
mellitus (DM)
Diabetes
lethargy
Fever,
Fever, pain
hypotension
lethargy,
Fever,
dysuria
Lethargy,
Dysuria
lethargy
Fever,
tenderness
Fever,
hypotension
Fever,
pain
Fever, anuria,
lethargy
Fever,
Fever
Fever, sepsis
presentation
Clinical
acidosis
metabolic
hyperglycemia,
azotemia,
Leukocytosis
hyperglycemia
azotemia,
Leukocytosis
hyperglycemia
Leukocytosis,
Azotemia
NA
NA
azotemia
Leukocytosis
leukocytosis
Azotemia,
leukocytosis
Azotemia,
hyperglycemia
Azotemia,
hyperglycemia
Azotemia,
Azotemia
presentation
Laboratory
Summary of previously published cases of emphysematous pyelonephritis in renal allografts
E. coli
E. coli
NA
NA
NA
NA
5 days
Imipenem,
14 days
Cephalothin,
15 days NA
lococcus E. coli
+ piperacillin, Staphy-
Ciprofloxacin
35 days
Ciprofloxacin,
NA
NA
>14 days
+ amikacin,
Cefotaxime
NA
antibiotics
3 day IV
ampicillin
Tobramycin,
NA
NA
treatment time
Antibiotics and
Staphylococcus
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
resistance
Antibiotic
+ vancomycin
NA
NA
NA
NA
Negative
E. coli
E. coli
NA
E. coli
bacilli
negative
Gram-
culture
Tissue
negative
Coagulase-
Negative
NA
NA
Negative
E. coli
E. coli
E. coli
E. coli
NA
Blood culture
negative
Coagulase-
K. pneumoniae
pneumoniae
Klebsiella
E. coli
Enterobacter
E. coli
E. coli
E. coli
Escherichia coli
NA
Urine culture
(estimated)
2
2
1
1
NA
NA
2
3
2
2
NA
3
classification
Al-Geizawi
PCD day 2
PCD day 3
day 10
Nephrectomy
Antibiotics
day 2
Nephrectomy
PCD
Antibiotics
day 21
Nephrectomy
day 4
Nephrectomy
PCD day 3
day 17
Nephrectomy
day 14
Nephrectomy
Treatment
Recovered
Recovered
On dialysis
Recovered
Died
Recovered
Recovered
Died
On dialysis
Recovered
On dialysis
On dialysis
Outcome
Agreda Castan~eda et al: Emphysematous pyelonephritis in renal allograft
Transplant Infectious Disease 2014: 16: 642–647 lethargy
prednisone
prednisolone
prednisone
lethargy
anuria
lethargy,
Fever,
hyperglycemia
azotemia,
Leukocytosis,
azotemia
Leukocytosis,
azotemia
leukocytosis,
acidosis,
Metabolic
azotemia
E. coli
K. pneumoniae
K. pneumoniae
Table 3
M, male; F, female; NA, not available; IV, intravenous; PCD, percutaneous drainage; PO, oral.
report)
mofetil,
Tacrolimus,
DM
pain,
Fever,
nausea,
mofetil,
Cyclosporine,
hypotension,
Fever,
anuria
mycophenolate
Tacrolimus,
azathioprine,
Type 2
Negative
E. coli
K. pneumoniae
Negative
E. coli
NA
capillosus
Bacteroides
E. coli
NA
NA
NA
NA
NA
NA
NA
NA
NA
resistance
Antibiotic
+ piperacillin-
Levofloxacin
+ gentamicin
Vancomycin
Cefmetazole
ciprofloxacin
then 6 weeks PO
+ metronidazole,
imipenem
2 weeks IV
NA
ciprofloxacin
42 days,
cefepime +
Imipenem,
E. coli
NA
K. pneumoniae
E. coli
K. pneumoniae
K. pneumoniae
resistance
No
NA
NA
4 weeks
tazobactam
IV piperacillin-
6 weeks
IV meropenem
4 weeks
PO ciprofloxacin
2 weeks then
tazobactam
IV piperacillin-
tazobactam
Piperacillin-
3
2
2
3
3
3
1
2
2
3
1
>15 days IV antibiotics
classification
Al-Geizawi
treatment time
Antibiotics and
25 days
NA
Leukocytosis,
K. pneumoniae
Negative
E. coli
E. coli
NA
Salmonella
NA
culture
Tissue
tazobactam,
azotemia
Leukocytosis,
Leukocytosis
hyperglycemia
count,
low platelet
azotemia,
E. coli
E. coli
E. coli
+ Enterobacter
Salmonella
NA
Blood culture
prednisone Fever,
Fever
sepsis
Fever,
hypotensi on
pain,
Leukocytosis,
hyperglycemia
azotemia,
Leukocytosis,
NA
Salmonella
E. coli
Urine culture
mofetil,
mycophenolate
Cyclosporine,
immunosuppression
Not on
transplant
Post-
Type 2
Type 2
Type 2
No
mofetil,
DM prednisone
mycophenolate
Tacrolimus, Fever,
oliguria
prednisone
pain,
mofetil,
Fever,
mycophenolate
Cyclosporine,
sepsis
prednisone
intravascular
Disseminated
hyperglycemia,
Azotemia,
azotemia
Leukocytosis,
presentation
Laboratory
coagulation,
anuria
Pain,
hematuria
Lethargy,
vomiting
pain,
Fever,
presentation
Clinical
mofetil,
mycophenolate
Cyclosporine,
transplant
Post-
Type 2
Type 2
prednisone
Cyclosporine,
(Current
No
No
No
No
No
No
No
No
No
Type 1
prednisone
et al.
12 months
9 years
15 months
10 months
10 years
embolization)
allograft
on dialysis,
months
(last 5
11 years
12 years
4 years
2 years
No
Tacrolimus,
mycophenolate
74, F
51, F
58, F
55, M
76, M
40, M
51, M
52, F
61, M
15 months
No
Immunosuppression
Casta~ neda
Agreda
et al. (6)
Alexander
et al. (2)
Al-Geizawi
et al. (24)
Schmidt
et al. (23)
Boltan
et al. (22)
Ortiz
et al. (1)
Chuang
et al. (21)
Baliga
et al. (20)
Arai
et al. (19)
Fujita
49, F
No
(DM)
mellitus
mofetil,
5 months
obstruction
Diabetes
Al-Akash (18)
12, M
Al-Makadma
transplant
Urinary
mycophenolate
gender
(ref)
Time after
and
years,
Author
Age in
Table 3 Continued
day 2
Nephrectomy
PCD day 1
PCD day 1
day 1
Nephrectomy
day 18
Nephrectomy
day 1
Nephrectomy
PCD day 1
Antibiotics
day 4
Nephrectomy
day 1
Nephrectomy
Antibiotics
Treatment
On dialysis
Recovered
Recovered
On dialysis
On dialysis
On dialysis
Recovered
Recovered
hepatitis)
fulminant
(because of
Died
On dialysis
Recovered
Outcome
Agreda Castan~eda et al: Emphysematous pyelonephritis in renal allograft
645
Agreda Castan~eda et al: Emphysematous pyelonephritis in renal allograft
Renal allografts are also unique in that they lack an investing Gerota’s fascia, which may act as a strong barrier to the spread of infection in native kidneys (2). Besides this, the renal parenchyma involvement is not evaluated in this classification, which is very important when you are looking to preserve renal function. Al-Geizawi et al. (2) have proposed a new schema for EPNs in renal allografts (Table 2), but this needs to be validated prospectively. They also propose treatment according to the stage. According to this classification, our patient warranted an allograft nephrectomy. In Western literature, there are only 23 published cases (including our current report) of allograft EPN (Table 3) (1, 2, 6–24). In these reports, 83% of patients were diabetic, and E. coli was the most common isolated bacteria (56%) followed by K. pneumoniae (22%). The timing from renal transplantation to allograft EPN ranged from 2 weeks to 12 years. In the reported cases, there were no signs of urinary obstruction, which makes us think that, in allograft EPN, obstruction is not a main feature. Of 23 patients, 12 were treated with allograft nephrectomy (52%), 7 (30%) patients underwent percutaneous drainage (PCD), and the remaining 4 cases (17%) were treated only with antibiotics and general management (these 4 cases were all Al-Geizawi Stage 1–2). All cases categorized as Al-Geizawi Stage 3 (7 cases), had radical surgery as preferred treatment. In Stage 2 (9 cases), 5 were treated with PCD plus antibiotics and 2 underwent surgery. In Stage 1 (4 cases), 2 were treated with antibiotics, 1 with PCD, and 1 required surgery. Three patients (13%) died. One patient underwent delayed nephrectomy (day 21), 1 died because of a fulminant hepatitis in critical care unit, and the last patient died even though an allograft nephrectomy was performed in 48 h. We suspect that the incidence of EPN in renal allografts is underreported, especially in patients with poor outcomes, so the above mortality rate may underestimate the actual lethality of this condition. Basic resuscitation measures of oxygen, intravenous fluids, acid-base balance correction, and appropriate antibiotics should be commenced along with good glycemic control. If there is any sign of multi-organ failure, the patient must be transferred to an intensive care unit (25). In our case the clinical presentation is as expected: a diabetic patient with inadequate glycemic controls, fever, and impaired consciousness. The clinical evolution and the CT (Stage 3) led us to a radical treatment, allograft nephrectomy. PCD has emerged as the primary treatment option, even in cases with massive allograft parenchymal
646
involvement (2, 6). This therapeutic option should be used in selected cases. If there is any doubt of the clinical course or if the initial diagnosis is Stage 3, an early allograft nephrectomy is a good option. A high degree of clinical suspicion, immediate CT scanning, and paired medical-surgical management, are the bases of the treatment of this severe disease. PCD procedure should be done within the first 48 h, and nephrectomy should not be delayed if there is an inadequate clinical course (6). The rarity of EPN and the lack of prospective validation of the new staging system prevent definitive conclusions from being reached via controlled prospective studies.
Conclusions EPN is a rare and potentially serious infection in the renal allograft and needs a high degree of suspicion for diagnosis. Timely management and early CT scanning will help in greater preservation of renal allografts. Antibiotics with or without PCD are the best option for Stages 1–2. Allograft nephrectomy is a good choice in extensive disease (Stage 3) or if the clinical course is inadequate.
References 1. Chuang YW, Chen CH, Cheng CH, et al. Severe emphysematous pyelonephritis in a renal allograft: successful treatment with percutaneous drainage and antibiotics. Clin Nephrol 2007; 68 (1): 42–46. 2. Al-Geizawi SM, Farney AC, Rogers J, et al. Renal allograft failure due to emphysematous pyelonephritis: successful non-operative management and proposed new classification scheme based on literature review. Transpl Infect Dis 2010; 12 (6): 543–550. 3. Somani BK, Nabi G, Thorpe P, et al. Is percutaneous drainage the new gold standard in the management of emphysematous pyelonephritis? Evidence from a systematic review. J Urol 2008; 179 (5): 1844–1849. 4. Huang JJ, Tseng CC. Emphysematous pyelonephritis: clinicoradiological classification, management, prognosis, and pathogenesis. Arch Intern Med 2000; 160 (6): 797–805. 5. Michaeli J, Mogle P, Perlberg S, Heiman S, Caine M. Emphysematous pyelonephritis. J Urol 1984; 131 (2): 203–208. 6. Alexander S, Varughese S, David VG, et al. Extensive emphysematous pyelonephritis in a renal allograft treated conservatively: case report and review of the literature. Transpl Infect Dis 2012; 14 (6): E150–E155. 7. Parameswaran R, Feest T. Gas nephrogram: an unusual complication of renal transplantation. Br J Radiol 1977; 50 (594): 438–440. 8. Brenbridge AN, Buschi AJ, Cochrane JA, Lees RF. Renal emphysema of the transplanted kidney: sonographic appearance. Am J Roentgenol 1979; 132 (4): 656–658.
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9. Balsara VJ, Raval B, Maklad NF. Emphysematous pyelonephritis in a renal transplant: sonographic and computed tomographic features. J Ultrasound Med 1985; 4 (2): 97–99. 10. Potter JL, Sullivan BM, Flournoy JG, Gerza C. Emphysema in the renal allograft. Radiology 1985; 155 (1): 51–52. 11. O’Donnell D, Rumbak M, Anderson J. Emphysematous pyelonephritis in a transplanted kidney. Clin Nephrol 1986; 25 (1): 52–53. 12. Glen D, Bayliss AP, Robertson EM. Percutaneous drainage in emphysematous pyelonephritis. Clin Radiol 1989; 40 (4): 434. 13. Kalra OP, Malik N, Minz M, Gupta KL, Sakhuja V, Chugh KS. Emphysematous pyelonephritis and cystitis in a renal transplant recipient–computed tomographic appearance. Int J Artif Organs 1993; 16 (1): 41–44. 14. Akalin E, Hyde C, Schmitt G, Kaufman J, Hamburger RJ. Emphysematous cystitis and pyelitis in a diabetic renal transplant recipient. Transplantation 1996; 62 (7): 1024–1026. 15. Goral S, Stone W. Emphysematous pyelonephritis in a nonfunctioning renal allograft of a patient undergoing hemodialysis. Am J Med Sci 1997; 314 (5): 354–356. 16. Cheng YT, Wang HP, Hsieh HH. Emphysematous pyelonephritis in a renal allograft: successful treatment with percutaneous drainage and nephrostomy. Clin Transplant 2001; 15 (5): 364–367. 17. Iqubal M, John GT, Gopalakrishnan G, Jacob CK. Abdominal gas is not always bowel associated: lessons from an allograft recipient. Nephrol Dial Transplant 2004; 19 (2): 503–504.
18. Al-Makadma AS, Al-Akash SI. An unusual case of pyelonephritis in a pediatric renal transplant recipient. Pediatr Transplant 2005; 9 (2): 258–260. 19. Fujita S, Watanabe J, Reed AI, et al. Case of emphysematous pyelonephritis in a renal allograft. Clin Transplant 2005; 19 (4): 559–562. 20. Arai S, Makino T, Okugi H, et al. A case of emphysematous pyelonephritis in a renal allograft. Transplantation 2006; 81 (2): 296–297. 21. Baliga KV, Narula AS, Sharma A, et al. Successful medical treatment of emphysematous pyelonephritis in a renal allograft recipient. Ren Fail 2007; 29 (6): 755–758. 22. Ortiz A, Petkov V, Urbano J, et al. Emphysematous pyelonephritis in dialysis patient after embolization of failed allograft. Urology 2007; 70 (2): 372 e17–e19. 23. Boltan LE, Randall H, Barri YM. Iatrogenic emphysematous pyelonephritis in a renal transplant patient. Transpl Infect Dis 2008; 10 (6): 409–412. 24. Schmidt S, Foert E, Zidek W, van der Giet M, Westhoff TH. Emphysematous pyelonephritis in a kidney allograft. Am J Kidney Dis 2009; 53 (5): 895–897. 25. Ubee SS, McGlynn L, Fordham M. Emphysematous pyelonephritis. BJU Int 2011; 107 (9): 1474–1478.
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647
Case report
Extensive emphysematous pyelonephritis in a renal allograft: case report and review of literature ~eda, D. Lorente, E. Trilla Herrera, C. Gasanz F. Agreda Castan Serrano, P. Servian Vives, I. Iztueta Saavedra, J. Morote Robles. Extensive emphysematous pyelonephritis in a renal allograft: case report and review of literature. Transpl Infect Dis 2014: 16: 642–647. All rights reserved Abstract: Emphysematous pyelonephritis (EPN) is an acute, severe necrotizing infection of the renal parenchyma and perirenal tissue, which results in the presence of gas within the renal parenchyma, collecting system, or perinephric tissue. EPN of renal allograft is rare, with only 23 cases reported in Western literature. Here, we report a patient treated successfully with surgery. We also review the literature, focusing on old and new suggested classification systems for EPN.
F. Agreda Castan~eda, D. Lorente, E. Trilla Herrera, C. Gasanz Serrano, P. Servian Vives, I. Iztueta Saavedra, J. Morote Robles Department of Urology, Vall d0 Hebron Hospital, Barcelona, Barcelona, Spain Key words: emphysematous pyelonephritis; kidney transplant; urinary tract infection; classification system; allograft nephrectomy Correspondence to: Fernando Agreda Casta~neda, Department of Urology, Vall d0 Hebron Hospital, Barcelona, Passeig de la Vall d’Hebron, 119, Barcelona 08035, Spain Tel: (+34) 622 409 780 E-mail: [email protected]
Received 16 January 2014, revised 3 March 2014, accepted for publication 9 March 2014 DOI: 10.1111/tid.12246 Transpl Infect Dis 2014: 16: 642–647
Emphysematous pyelonephritis (EPN) is an acute, severe necrotizing infection of the renal parenchyma and perirenal tissue, which results in the presence of gas within the renal parenchyma, collecting system, or perinephric tissue (1). EPN of renal allograft is rare, with only 23 cases reported in Western literature. Here, we report a patient treated successfully with surgery.
Case report A 74-year-old woman, with history of hypertension, poorly controlled insulin-dependent diabetes, and dyslipidemia, developed end-stage renal disease. She received maintenance hemodialysis from 2010 for 2 years before undergoing expanded-criteria deceased-donor kidney transplantation in March 2012. She shared 3 human leukocyte antigen identities with the kidney donor (A, B, and DR). She experienced
642
adequate allograft postoperative function and was discharged with serum creatinine level of 1.78 mg/dL. On routine follow-up visits, no complication was observed, and no hospital readmission was needed. She was on triple immunosuppression with prednisone, tacrolimus, and mycophenolate mofetil. On her last clinic visit, 1 month before admission, she had a baseline serum creatinine level of 1.3 mg/dL. One year after transplantation, she presented to her family practitioner with fever of 3 days’ duration. She could not control her blood sugar levels for 2 days (always high in rapid test machine). The patient was admitted to a third-level hospital. On arrival she was drowsy, had a temperature of 38°C, blood pressure of 90/60 mmHg, tachycardia of 110 bpm, and 10 h of anuria. Laboratory findings showed serum glucose of 715 mg/dL, urea 151 mg/dL, serum creatinine 5.34 mg/dL, sodium 121 mEq/dL, potassium 5.04 mEq/dL,
Agreda Castan~eda et al: Emphysematous pyelonephritis in renal allograft
and leukocyte count of 17000/mL with 90% neutrophils. Venous analysis showed pH of 7.3 and bicarbonate level of 9 mmol/L. Urinalysis revealed >100 red blood cells per high-power field. She was admitted to the intensive care unit and started on intravenous piperacillin-tazobactam with a provisional diagnosis of urosepsis. She underwent hemodialysis because of anuria and signs of volume overload. Within 24 h of admission, Escherichia coli grew in urine and blood cultures. Computed tomography (CT) of the abdomen revealed an EPN of the renal allograft, with >50% of the renal parenchyma involved and no dilatation of collecting system, classified as Stage 3 (Al-Geizawi et al. [2], Fig. 1). The patient was then transferred to the renal transplant team, and a renal allograft nephrectomy was performed, 48 h after initial admission. After surgery and for 48 h, the patient was under noradrenalin treatment and started hemodialysis through a jugular venous catheter. Two weeks after surgery, she had a fever episode. A CT scan was performed, and showed a liquid collection of 6 cm, which was successfully drained percutaneously. Three weeks after admission, the patient was discharged, on a maintenance hemodialysis program. To the date of this report, no further complications were observed and the patient is back on the deceaseddonor kidney transplantation waiting list.
a risk factor for EPN, and women are more commonly affected than men in a ratio of 4:1. Gas-forming organisms, especially E. coli, and then Klebsiella pneumoniae, are most commonly seen in EPN. It is believed that with severe infection, areas of ischemic injury develop. The presence of necrotic tissue with high glucose concentration provides the ideal environment for such organisms to ferment glucose to lactose, carbon dioxide, and hydrogen, resulting in the clinical entity known as EPN (3). The clinical presentation of EPN is usually that of severe pyelonephritis that rapidly progresses to sepsis with multiple organ failure. Although evidence of EPN can be seen on plain radiographs and ultrasound, the gold standard for the diagnosis and staging of EPN is CT scanning (4). EPN classifications usually have been based on imaging. The first classification used plain abdominal x-rays (5), but the newer systems are based in CT scanning. The most commonly used, in this decade, is the Huang and Tseng classification (4) (Table 1). Unfortunately, no cases of EPN after kidney transplantation were included in their series. Consequently, this staging system is not really applicable to the management of EPN in transplanted kidneys, because all cases of EPN in renal allografts would be categorized as Stage 4. EPN classification according to Huang and Tseng (3)
Discussion EPN is a necrotizing infection of the kidney and its surroundings, defined by the presence of gas in the renal parenchyma, collecting system, or perinephric space (1). EPN is most commonly encountered in diabetics, with >80% of reported cases occurring in diabetic patients (3). Urinary tract obstruction is clearly
1
Gas in collecting system only
2
Parenchymal gas only
3A
Extension of gas into perinephric space
3B
Extension of gas into pararenal space
4
EPN in solitary kidney or bilateral disease
EPN, emphysematous pyelonephritis.
Table 1
EPN of renal allograft according to Al-Geizawi et al. (2)
Fig. 1. Renal allograft in right iliac fossa (circle). Parenchymal involvement is almost 90%, Al-Geizawi Stage 3 (2).
Stage 1
Gas in the collecting system
Stage 2
Gas replacing 50% of renal parenchyma; or extensive spread of infection in the perinephric area; or patient with evidence of multiple organ failure, uncontrolled sepsis, or shock not responding to medical management
EPN, emphysematous pyelonephritis.
Table 2
Transplant Infectious Disease 2014: 16: 642–647
643
644
Transplant Infectious Disease 2014: 16: 642–647
Table 3
et al. (17)
Iqubal
et al. (16)
Cheng
Stone (15)
Goral and
et al. (14)
Akalin
et al. (13)
Kalra
et al. (12)
Glen
et al. (11)
O’Donnell
et al. (10)
Potter
et al. (10)
Potter
et al. (9)
Balsara
et al. (8)
Brenbridge
and Feest (7)
Parameswaran
Author (ref)
38, F
55, M
55, F
62, M
35, M
66, F
27, M
39, M
31, F
32, M
33, M
53, F
gender
years,
Age in
2 years
7 years
dialysis)
months on
(last 8
5.5 years
5 years
3 months
NA
5 years
5 weeks
20 months
6 weeks
2 weeks
7 weeks
transplant
Time after
No
No
No
No
NA
NA
NA
No
No
No
No
No
obstruction
Urinary
azathioprine, prednisolone
DM
Cyclosporine,
prednisone
Cyclosporine,
immunosuppression
Not on
prednisolone
azathioprine,
Cyclosporine,
NA
NA
NA
NA
NA
prednisone
Cyclosporine,
prednisone
Azathioprine,
prednisone
Azathioprine,
Immunosuppression
transplant
Post-
DM
transplant
Post-
Type 1
Type 1
No
Yes
Yes
Type 1
Type 1
DM
transplant
Post-
DM
transplant
Post-
DM
transplant
Post-
mellitus (DM)
Diabetes
lethargy
Fever,
Fever, pain
hypotension
lethargy,
Fever,
dysuria
Lethargy,
Dysuria
lethargy
Fever,
tenderness
Fever,
hypotension
Fever,
pain
Fever, anuria,
lethargy
Fever,
Fever
Fever, sepsis
presentation
Clinical
acidosis
metabolic
hyperglycemia,
azotemia,
Leukocytosis
hyperglycemia
azotemia,
Leukocytosis
hyperglycemia
Leukocytosis,
Azotemia
NA
NA
azotemia
Leukocytosis
leukocytosis
Azotemia,
leukocytosis
Azotemia,
hyperglycemia
Azotemia,
hyperglycemia
Azotemia,
Azotemia
presentation
Laboratory
Summary of previously published cases of emphysematous pyelonephritis in renal allografts
E. coli
E. coli
NA
NA
NA
NA
5 days
Imipenem,
14 days
Cephalothin,
15 days NA
lococcus E. coli
+ piperacillin, Staphy-
Ciprofloxacin
35 days
Ciprofloxacin,
NA
NA
>14 days
+ amikacin,
Cefotaxime
NA
antibiotics
3 day IV
ampicillin
Tobramycin,
NA
NA
treatment time
Antibiotics and
Staphylococcus
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
resistance
Antibiotic
+ vancomycin
NA
NA
NA
NA
Negative
E. coli
E. coli
NA
E. coli
bacilli
negative
Gram-
culture
Tissue
negative
Coagulase-
Negative
NA
NA
Negative
E. coli
E. coli
E. coli
E. coli
NA
Blood culture
negative
Coagulase-
K. pneumoniae
pneumoniae
Klebsiella
E. coli
Enterobacter
E. coli
E. coli
E. coli
Escherichia coli
NA
Urine culture
(estimated)
2
2
1
1
NA
NA
2
3
2
2
NA
3
classification
Al-Geizawi
PCD day 2
PCD day 3
day 10
Nephrectomy
Antibiotics
day 2
Nephrectomy
PCD
Antibiotics
day 21
Nephrectomy
day 4
Nephrectomy
PCD day 3
day 17
Nephrectomy
day 14
Nephrectomy
Treatment
Recovered
Recovered
On dialysis
Recovered
Died
Recovered
Recovered
Died
On dialysis
Recovered
On dialysis
On dialysis
Outcome
Agreda Castan~eda et al: Emphysematous pyelonephritis in renal allograft
Transplant Infectious Disease 2014: 16: 642–647 lethargy
prednisone
prednisolone
prednisone
lethargy
anuria
lethargy,
Fever,
hyperglycemia
azotemia,
Leukocytosis,
azotemia
Leukocytosis,
azotemia
leukocytosis,
acidosis,
Metabolic
azotemia
E. coli
K. pneumoniae
K. pneumoniae
Table 3
M, male; F, female; NA, not available; IV, intravenous; PCD, percutaneous drainage; PO, oral.
report)
mofetil,
Tacrolimus,
DM
pain,
Fever,
nausea,
mofetil,
Cyclosporine,
hypotension,
Fever,
anuria
mycophenolate
Tacrolimus,
azathioprine,
Type 2
Negative
E. coli
K. pneumoniae
Negative
E. coli
NA
capillosus
Bacteroides
E. coli
NA
NA
NA
NA
NA
NA
NA
NA
NA
resistance
Antibiotic
+ piperacillin-
Levofloxacin
+ gentamicin
Vancomycin
Cefmetazole
ciprofloxacin
then 6 weeks PO
+ metronidazole,
imipenem
2 weeks IV
NA
ciprofloxacin
42 days,
cefepime +
Imipenem,
E. coli
NA
K. pneumoniae
E. coli
K. pneumoniae
K. pneumoniae
resistance
No
NA
NA
4 weeks
tazobactam
IV piperacillin-
6 weeks
IV meropenem
4 weeks
PO ciprofloxacin
2 weeks then
tazobactam
IV piperacillin-
tazobactam
Piperacillin-
3
2
2
3
3
3
1
2
2
3
1
>15 days IV antibiotics
classification
Al-Geizawi
treatment time
Antibiotics and
25 days
NA
Leukocytosis,
K. pneumoniae
Negative
E. coli
E. coli
NA
Salmonella
NA
culture
Tissue
tazobactam,
azotemia
Leukocytosis,
Leukocytosis
hyperglycemia
count,
low platelet
azotemia,
E. coli
E. coli
E. coli
+ Enterobacter
Salmonella
NA
Blood culture
prednisone Fever,
Fever
sepsis
Fever,
hypotensi on
pain,
Leukocytosis,
hyperglycemia
azotemia,
Leukocytosis,
NA
Salmonella
E. coli
Urine culture
mofetil,
mycophenolate
Cyclosporine,
immunosuppression
Not on
transplant
Post-
Type 2
Type 2
Type 2
No
mofetil,
DM prednisone
mycophenolate
Tacrolimus, Fever,
oliguria
prednisone
pain,
mofetil,
Fever,
mycophenolate
Cyclosporine,
sepsis
prednisone
intravascular
Disseminated
hyperglycemia,
Azotemia,
azotemia
Leukocytosis,
presentation
Laboratory
coagulation,
anuria
Pain,
hematuria
Lethargy,
vomiting
pain,
Fever,
presentation
Clinical
mofetil,
mycophenolate
Cyclosporine,
transplant
Post-
Type 2
Type 2
prednisone
Cyclosporine,
(Current
No
No
No
No
No
No
No
No
No
Type 1
prednisone
et al.
12 months
9 years
15 months
10 months
10 years
embolization)
allograft
on dialysis,
months
(last 5
11 years
12 years
4 years
2 years
No
Tacrolimus,
mycophenolate
74, F
51, F
58, F
55, M
76, M
40, M
51, M
52, F
61, M
15 months
No
Immunosuppression
Casta~ neda
Agreda
et al. (6)
Alexander
et al. (2)
Al-Geizawi
et al. (24)
Schmidt
et al. (23)
Boltan
et al. (22)
Ortiz
et al. (1)
Chuang
et al. (21)
Baliga
et al. (20)
Arai
et al. (19)
Fujita
49, F
No
(DM)
mellitus
mofetil,
5 months
obstruction
Diabetes
Al-Akash (18)
12, M
Al-Makadma
transplant
Urinary
mycophenolate
gender
(ref)
Time after
and
years,
Author
Age in
Table 3 Continued
day 2
Nephrectomy
PCD day 1
PCD day 1
day 1
Nephrectomy
day 18
Nephrectomy
day 1
Nephrectomy
PCD day 1
Antibiotics
day 4
Nephrectomy
day 1
Nephrectomy
Antibiotics
Treatment
On dialysis
Recovered
Recovered
On dialysis
On dialysis
On dialysis
Recovered
Recovered
hepatitis)
fulminant
(because of
Died
On dialysis
Recovered
Outcome
Agreda Castan~eda et al: Emphysematous pyelonephritis in renal allograft
645
Agreda Castan~eda et al: Emphysematous pyelonephritis in renal allograft
Renal allografts are also unique in that they lack an investing Gerota’s fascia, which may act as a strong barrier to the spread of infection in native kidneys (2). Besides this, the renal parenchyma involvement is not evaluated in this classification, which is very important when you are looking to preserve renal function. Al-Geizawi et al. (2) have proposed a new schema for EPNs in renal allografts (Table 2), but this needs to be validated prospectively. They also propose treatment according to the stage. According to this classification, our patient warranted an allograft nephrectomy. In Western literature, there are only 23 published cases (including our current report) of allograft EPN (Table 3) (1, 2, 6–24). In these reports, 83% of patients were diabetic, and E. coli was the most common isolated bacteria (56%) followed by K. pneumoniae (22%). The timing from renal transplantation to allograft EPN ranged from 2 weeks to 12 years. In the reported cases, there were no signs of urinary obstruction, which makes us think that, in allograft EPN, obstruction is not a main feature. Of 23 patients, 12 were treated with allograft nephrectomy (52%), 7 (30%) patients underwent percutaneous drainage (PCD), and the remaining 4 cases (17%) were treated only with antibiotics and general management (these 4 cases were all Al-Geizawi Stage 1–2). All cases categorized as Al-Geizawi Stage 3 (7 cases), had radical surgery as preferred treatment. In Stage 2 (9 cases), 5 were treated with PCD plus antibiotics and 2 underwent surgery. In Stage 1 (4 cases), 2 were treated with antibiotics, 1 with PCD, and 1 required surgery. Three patients (13%) died. One patient underwent delayed nephrectomy (day 21), 1 died because of a fulminant hepatitis in critical care unit, and the last patient died even though an allograft nephrectomy was performed in 48 h. We suspect that the incidence of EPN in renal allografts is underreported, especially in patients with poor outcomes, so the above mortality rate may underestimate the actual lethality of this condition. Basic resuscitation measures of oxygen, intravenous fluids, acid-base balance correction, and appropriate antibiotics should be commenced along with good glycemic control. If there is any sign of multi-organ failure, the patient must be transferred to an intensive care unit (25). In our case the clinical presentation is as expected: a diabetic patient with inadequate glycemic controls, fever, and impaired consciousness. The clinical evolution and the CT (Stage 3) led us to a radical treatment, allograft nephrectomy. PCD has emerged as the primary treatment option, even in cases with massive allograft parenchymal
646
involvement (2, 6). This therapeutic option should be used in selected cases. If there is any doubt of the clinical course or if the initial diagnosis is Stage 3, an early allograft nephrectomy is a good option. A high degree of clinical suspicion, immediate CT scanning, and paired medical-surgical management, are the bases of the treatment of this severe disease. PCD procedure should be done within the first 48 h, and nephrectomy should not be delayed if there is an inadequate clinical course (6). The rarity of EPN and the lack of prospective validation of the new staging system prevent definitive conclusions from being reached via controlled prospective studies.
Conclusions EPN is a rare and potentially serious infection in the renal allograft and needs a high degree of suspicion for diagnosis. Timely management and early CT scanning will help in greater preservation of renal allografts. Antibiotics with or without PCD are the best option for Stages 1–2. Allograft nephrectomy is a good choice in extensive disease (Stage 3) or if the clinical course is inadequate.
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