© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Transplant Infectious Disease, ISSN 1398-2273

Case report

Candida arteritis in kidney transplant recipients: case report and review of the literature  , Ł. Chrobak, B. Bzoma, A. Perkowska, A. Dez bska-Slizie n D. Zadroz_ ny, A. Chamienia, J. Kostro, A. Milecka, M. Bronk,  ski, B. Rutkowski. Candida arteritis in kidney transplant Z. Sledzi n recipients: case report and review of the literature. Transpl Infect Dis 2015: 17: 449–455. All rights reserved

 n1, Ł. Chrobak1, B. A. Dez bska-Slizie 1 Bzoma , A. Perkowska2, D. Zadroz_ ny3, A. Chamienia1, J. Kostro3, A. Milecka3,  nski3, M. Bronk4, Z. Sledzi 1 B. Rutkowski

Abstract: Multi-organ procurement is a risk factor for contamination of preservation fluid with intestinal flora including fungi (e.g., Candida). Transmission of fungal species to the graft vessel can cause mycotic arteritis. This is a very rare but lifethreatening complication of renal transplantation. We present 2 cases of renal transplant recipients from the same multi-organ donor. Both recipients suffered from severe hemorrhages from renal graft anastomosis and renal artery pseudoaneurysm due to Candida albicans arteritis (CAA). The culture of the preservation fluid revealed growth of Escherichia coli, but neither preservation fluid nor multiple routine blood cultures performed before hemorrhagic complications revealed fungal growth (media nonselective for fungal growth were applied). The first recipient suffered from sudden severe hemorrhage in the area of graft anastomosis on day 10 post surgery (without any preceding clinical or radiological symptoms). This led to urgent surgery and graftectomy, which was complicated by cardio-respiratory arrest with resuscitation in the operating room; despite resuscitation, irreversible brain damage, and subsequent death occurred in the intensive care unit (ICU) 2 weeks later (on day 24 after transplantation). The second patient underwent urgent vascular surgery on day 22 (after transplantation), because of hemorrhage from a pseudoaneurysm of the graft artery. She required repeated vascular operations, extended antimicrobial and antifungal therapy, and ICU monitoring and, despite these interventions, she died on day 80 after transplantation as a result of Pseudomonas aeruginosa sepsis. Arteritis of the renal artery in both patients was caused by C. albicans. This was confirmed by histopathology: infiltration of renal artery with budding yeast forming pseudohyphae (Case 1), and the presence of C. albicans in the culture of the renal artery and surrounding tissue (Case 2). We conclude that organ preservation solution should be cultured with use of media selective for fungal growth. As soon as the positive culture is detected, appropriate measures protecting patients against CAA should be undertaken.

1

Solid organ transplantation recipients are at risk for invasive fungal infections. Candida and Aspergillus species were reported as the most common fungal pathogens associated with invasive disease in organ recipients at 59.0% and 24.8%, respectively (1, 2). One of

Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland, 2 Department of Transplantation Medicine and Nephrology, Transplantation Institute, Medical University of Warsaw, Warszawa, Poland, 3Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Gdansk, Poland, 4Department of Clinical Microbiology, University Clinical Center of Gdansk, Gdansk, Poland

Key words: renal transplant; infection; arteritis; Candida albicans; mycotic arteritis Correspondence to: Alicja Dez bska-Slizien, Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, ul. Dez binki 7, Gdansk 80-952, Poland Tel: +48 58 349 25 58 Fax: +48 58 349 25 51 E-mail: [email protected]

Received 29 December 2014, revised 12 March 2015, accepted for publication 20 March 2015 DOI: 10.1111/tid.12388 Transpl Infect Dis 2015: 17: 449–455

the life-threatening forms of invasive fungal infection in renal transplant recipients is mycotic arteritis. Candida albicans and (rarely) Aspergillus cause mycotic arteritis, which compromises the renal graft anastomosis (3, 4). This complication is rare (1 case per 1000 grafts), but

449

 Dez bska-Slizie n et al: Candida arteritis in renal transplants

potentially life-threatening, because it usually leads to anastomotic leaks or arterial wall rupture with or without aneurysm formation (5). Mycotic arteritis can result in hemorrhagic shock necessitating emergency nephrectomy. Repair of a mycotic aneurysm has high morbidity, and often results in graft loss (6, 7). The source of fungal infection may be a true donor-to-host transmission or, more commonly, contamination with intestinal flora during organ procurement. This infection can lead to hematogenous or local spread of yeast to the arterial wall (8). Early recognition of C. albicans arteritis (CAA) is difficult. Mycotic arteritis may take place even in patients with no evidence of candiduria or candidemia or preceding clinical symptoms and radiological features. Therefore, it may be of great importance to perform routine cultures of organ preservation solution on a medium selective for fungal growth. This measure may allow early intervention by appropriate aggressive antifungal therapy, strict radiologic surveillance of graft anastomosis, and eventual surgical intervention in cases where pseudoaneurysm at the site of renal implantation is diagnosed. We describe 2 patients who underwent renal transplantation from the same multi-organ donor and who, during the early post-transplant period, both developed CAA.

Case reports Case 1 A 44-year-old man underwent renal transplantation after 7 years on maintenance hemodialysis. The underlying kidney disease was chronic glomeluronephritis (mesangial-proliferative type) diagnosed at 23 years of age. The recipient suffered from the following co-morbidities, which were diagnosed and cured while he was dialyzed: rupture of left kidney (nephrectomy); papillary adenocarcinoma in right kidney (nephrectomy); nodular goiter (thyroidectomy); secondary hyperparathyroidism (subtotal hyperpathroidectomy performed twice without effect, and treated with cinacalcet and sevelamer); cholelithiasis (cholecystectomy); anemia (erythropoiesis-stimulating agents); and arterial hypertension (treated with amlodipine). Transplantation details are as follows: 4 human leukocyte antigen mismatches, panel-reactive antibody 10%, and total ischemia time 14 h 44 min. No surgical problems occurred during the implantation procedure. Immunosuppressive protocol consisted of methylprednisolone, mycophenolate mofetil, and tacrolimus; antimicrobial prophylaxis consisted of ceftriaxone,

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trimethoprim-sulfamethoxazole, valganciclovir, and nystatin. During the post-transplant follow-up, anuria and delayed graft function were observed. On postoperative day 2, transient increase in body temperature (37.8°C) and elevation of C-reactive protein (CRP) level were noticed, and information on Escherichia coli growth in the preservation medium was received. On postoperative day 5, because of suspicion of acute rejection, based on the clinical picture (anuria), and increased resistance index on Doppler ultrasound (US), pulses of methylprednisolone were given. After that treatment, US of the kidney graft revealed improvement of resistance index and no aneurysmic lesions on any of the 5 following examinations. The patient remained in a good clinical condition (normal body temperature, CRP within normal range, no clinical or laboratory signs of infection), although he required hemodialysis because of anuria. On day 10 after transplantation, the patient suddenly complained of diffuse abdominal pain radiating to the right leg. The clinical examination revealed abdominal distension with generalized tenderness and massive wound bleeding. Despite saline and packed red blood cells transfusion (universal in emergency state: O Rh–), cardiovascular collapse and cardiac arrest were observed in the operating room. The patient was resuscitated successfully with further transfusions (a total of 13 units of packed red blood cells). During surgery, dehiscence of the arterial anastomosis was found and the renal graft was removed. No further problems with bleeding or wound healing were noted after graftectomy. Unfortunately, the patient remained comatose after surgery and was diagnosed with cerebral pontine herniation, which subsequently resulted in his death 2 weeks later. Standard bacteriology workup of the recipient was performed after transplantation and, despite multiple cultures, no infection was detected prior to the hemorrhage. Further cultures of blood, Redon drain content, and aspirate from the intubation tube revealed C. albicans growth (Table 1). Histopathologic examination of the removed graft revealed exclusively acute tubular necrosis. In the renal artery wall, periodic acid-Schiff staining revealed budding yeast, forming pseudohyphae, typical of C. albicans infection (Fig. 1).

Case 2 A 45-year-old woman underwent renal transplantation after 10 years on maintenance hemodialysis. The

Transplant Infectious Disease 2015: 17: 449–455

 Dez bska-Slizie n et al: Candida arteritis in renal transplants

Clinical picture, microbiology evaluation, and C-reactive protein (CRP) level performed in recipient of renal graft from the multi-organ donor (Case 1) CRP level (mg/dL)

Day

Clinical events and symptoms

1

Renal transplantation

2

No complaints

139

3

No complaints

5 7

Microbiology diagnostic material

Culture result



Antimicrobial treatment Ceftriaxone, TMP-SMX, valganciclovir, nystatin

Preservation fluid – medium non-selective for fungal growth

Escherichia coli

No change

79

Redon drain content Blood

Negative Negative

Piperacillin-tazobactam vancomycin, valganciclovir, nystatin

No complaints

43

Blood – peripheral 29 blood – central access

Negative Negative

No change

No complaints

16

Blood – peripheral

Negative

No change

Blood – peripheral

Negative

8

No complaints



10

Sudden severe hemorrhage, emergency vascular surgery, CPR

4.1

11

Coma, ICU



Nose cavity Redon drain content Endotracheal tube Blood – bullion culture

Negative Negative Negative Candida albicans

No change

15

Coma, ICU







Piperacillin-tazobactam vancomycin, valganciclovir, fluconazole

16

Coma, ICU



Redon drain content Blood – bullion culture Endotracheal tube

C. albicans C. albicans Negative

No change

22

Coma, ICU

310

Endotracheal tube

C. albicans, Pseudomonas aeruginosa

No change

24

Patient died

No change No change

CPR, cardiopulmonary resuscitation; ICU, intensive care unit; TMP-SMX, trimethoprim-sulfamethoxazole.

Table 1

underlying kidney disease was agenesis of the left kidney and unknown nephropathy of the right kidney. She did not suffer from any important co-morbidities. Transplantation details are as follows: 3 human leukocyte antigen mismatches, panel-reactive antibody 0%, and total ischemia time 10 h 42 min. No surgical problems occurred during the engraftment operation. Immunosuppressive protocol consisted of methylprednisolone, mycophenolate mofetil, and tacrolimus; antimicrobial prophylaxis consisted of ceftriaxone, trimethoprim-sulfamethoxazole, valganciclovir, and nystatin. During the early post-transplant follow-up, no complication was noticed. Graft function was excellent and rapid decrease in creatinine was observed. On day 12, a urinary tract infection was diagnosed (Enterococcus faecium), and vancomycin was added to the treatment.

All subsequent cultures were negative, and the patient was discharged home on day 20 (Table 2). All US examinations (5 scans) performed during the postoperative period revealed no pathology within the anastomosis site. She was readmitted 2 days later because of pain in the area of her graft. US revealed pseudoaneurysm close to the graft anastomosis, confirmed by computed tomography angiography. During surgical intervention, the aneurysm ruptured and was excised, and a new anastomosis was performed. At that time, CAA was not yet suspected, but the recipient received antifungal therapy (fluconazole). The patient did not require dialysis. Ten days later, while still in the hospital, the patient suddenly complained of diffuse abdominal pain. The clinical examination revealed abdominal distension

Transplant Infectious Disease 2015: 17: 449–455

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 Dez bska-Slizie n et al: Candida arteritis in renal transplants

Donor characteristics

Fig. 1. (Case 1.) Budding yeast and pseudohyphae in artery wall. Periodic acid-Schiff staining; original magnification 10009.

with generalized tenderness. During surgery, dehiscence of the arterial anastomosis was found and the renal graft was removed. C. albicans growth was noted in culture of the renal artery and surrounding tissue. At that time, the information about the positive microbiological cultures from both recipients was analyzed together, and the diagnosis of CAA in both recipients was confirmed. Despite extended antibiotic treatment (meropenem with vancomycin) and antifungal therapy (voriconazole, caspofungin, amphotericin), 3 additional vascular surgery interventions, including bypass surgery, were necessary, because of recurrence of aneurysms and bleeding from the anastomotic site. These surgeries were followed by septic shock caused by Pseudomonas aeruginosa and, despite intensive care, the patient died 80 days after transplantation, 15 days after the last surgical intervention. Also in this case, routine culture studies did not show any micro-organisms (except 1 positive urine culture) up to the first surgical revision. Culture studies performed later revealed growth of C. albicans in perigraft fluid collection, in excised renal artery, and in tissue specimens from the vascular interventions site.

Other organ recipient The recipient of the liver from the same multi-organ donor did not experience such complications. Culture of preservation solution was not performed. The liver transplantation was performed in another unit.

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The donor was a 54-year-old woman with cerebrovascular cause of death (intracranial hemorrhage). She spent 3 days in the intensive care unit before organ retrieval. According to the deceased-donor score, the donor was C category (9). Clinical and laboratory results were as follows: creatinine level 0.8 mg/dL, Cockroft–Gault creatinine clearance 82.95 mL/min, diuresis 200–300 mL/h, and CRP/procalcitonin within normal limits. No circulatory collapses or cardiac arrest occurred before organ retrieval. Growth of Streptococcus pneumoniae and C. albicans in aspirate from her endotracheal tube was noted. Blood and urine culture were negative. During a standard procurement procedure, 2 kidneys and the liver were retrieved, with no signs of any operating field contamination. Microbiologic testing of preservative kidney fluid was performed. The microbial study of the preservative kidney fluid included the following: plating agar (Columbia agar with sheep blood, Sabouraud agar) and liquid medium (brain-heart broth). Inoculation of Columbia sheep blood agar was incubated aerobically for 48 h at 35–37°C. Sabouraud agar was incubated for 7 days at 30°C. The plating was not performed in a broth selective for yeast. In this case, preservative kidney fluid culture on brain-heart broth and Columbia agar with sheep blood showed a rapid increase in E. coli, and the study was terminated. No growth of yeast was achieved on Sabouraud agar. In the absence of a test procedure using selective broth for yeasts, the presence of a small number of Candida species in the preservative solution could remain undetected.

Discussion Vascular infection is an infrequent but serious complication of renal transplantation. A limited number of CAA cases have been reported in renal transplant recipients (5, 6). Most of the diagnosed cases of CAA occurred early in the post-transplant period and these ‘early’ cases (up to 20 days) were usually complicated by massive bleeding requiring emergency surgical intervention and (most often) nephrectomy. However, graft-saving operations are possible in ‘late’ CAA cases (>2 months) not accompanied by life-threatening hemorrhage, when elective attempt and planned vascular surgery are possible (10). In our cases, CAA occurred within the first 3 weeks after transplantation. In both patients, nephrectomy was performed, although, in the second case, the first emergency surgery, which was performed without the suspicion of CAA, resulted in

Transplant Infectious Disease 2015: 17: 449–455

 Dez bska-Slizie n et al: Candida arteritis in renal transplants

Clinical picture, microbiology evaluation, and C-reactive protein (CRP) level performed in recipient of renal graft from the multi-organ donor (Case 2)

CRP level (mg/dL)

Microbiology diagnostic material

Day

Clinical events and symptoms

Culture result

Antimicrobial treatment

1

Renal transplantation

2

No complaints

104

3

No complaints

68

8

No complaints

8

Urine

Negative

No change

10

No complaints



Urine

Negative

No change

12

No complaints

9

Urine

Enterococcus faecium

Ceftriaxone, vancomycin, TMP-SMX, acyclovir, nystatin

16

No complaints



Urine

Negative

No change

20

Discharge from hospital

15





No change

22

Increased blood pressure and pain in the area of the graft Re-admission and re-operation for pseudoaneurysm

24

Urine Perigraft fluid collection

Negative Candida albicans

Meropenem, vancomycin, TMP-SMX, acyclovir, nystatin

27

Post surgery treatment

15

Urine

Negative

No change

31

Sudden severe hemorrhage and graftectomy

7

Artery

C. albicans

Meropenem, vancomycin, voriconazole, caspofungin

34

Vascular anastomosis reconstruction because of hemorrhage

126

Wound aspirate, tissue

C. albicans

No change

36

Post surgery treatment

100

Blood/Redon content

Negative

No change

42

Post surgery treatment

213

Wound aspirate

Negative

No change

Ceftriaxone, TMP-SMX, acyclovir, nystatin Preservation medium non-selective for fungal growth

Escherichia coli

No change

Redon drain content Blood Urine

Negative Negative Negative

No change

47–60

Post surgery treatment

125

Blood 49, urine 19

Negative

No change

61

Post surgery treatment

109





Meropenem, vancomycin, voriconazole, amphotericin

65

Bifemoral by-pass for aneurysm of external iliac artery







No change

67

Clinical deterioration

337

Redon drain content/blood

Pseudomonas aeruginosa

No change

68

Clinical deterioration

460





No change

70–77

Clinical deterioration

52

Blood 29, endotracheal tube

P. aeruginosa

No change

80

Patient died

TMP-SMX, trimethoprim-sulfamethoxazole.

Table 2

creation of a new anastomosis, but during the second intervention, the graft was removed. Reconstruction of a very narrow external iliac artery with a patch from

the saphenous vein in the first recipient was successful, and no further problems relating to recurrent bleeding or wound infection were noted; however, the

Transplant Infectious Disease 2015: 17: 449–455

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© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Transplant Infectious Disease, ISSN 1398-2273

Case report

Candida arteritis in kidney transplant recipients: case report and review of the literature  , Ł. Chrobak, B. Bzoma, A. Perkowska, A. Dez bska-Slizie n D. Zadroz_ ny, A. Chamienia, J. Kostro, A. Milecka, M. Bronk,  ski, B. Rutkowski. Candida arteritis in kidney transplant Z. Sledzi n recipients: case report and review of the literature. Transpl Infect Dis 2015: 17: 449–455. All rights reserved

 n1, Ł. Chrobak1, B. A. Dez bska-Slizie 1 Bzoma , A. Perkowska2, D. Zadroz_ ny3, A. Chamienia1, J. Kostro3, A. Milecka3,  nski3, M. Bronk4, Z. Sledzi 1 B. Rutkowski

Abstract: Multi-organ procurement is a risk factor for contamination of preservation fluid with intestinal flora including fungi (e.g., Candida). Transmission of fungal species to the graft vessel can cause mycotic arteritis. This is a very rare but lifethreatening complication of renal transplantation. We present 2 cases of renal transplant recipients from the same multi-organ donor. Both recipients suffered from severe hemorrhages from renal graft anastomosis and renal artery pseudoaneurysm due to Candida albicans arteritis (CAA). The culture of the preservation fluid revealed growth of Escherichia coli, but neither preservation fluid nor multiple routine blood cultures performed before hemorrhagic complications revealed fungal growth (media nonselective for fungal growth were applied). The first recipient suffered from sudden severe hemorrhage in the area of graft anastomosis on day 10 post surgery (without any preceding clinical or radiological symptoms). This led to urgent surgery and graftectomy, which was complicated by cardio-respiratory arrest with resuscitation in the operating room; despite resuscitation, irreversible brain damage, and subsequent death occurred in the intensive care unit (ICU) 2 weeks later (on day 24 after transplantation). The second patient underwent urgent vascular surgery on day 22 (after transplantation), because of hemorrhage from a pseudoaneurysm of the graft artery. She required repeated vascular operations, extended antimicrobial and antifungal therapy, and ICU monitoring and, despite these interventions, she died on day 80 after transplantation as a result of Pseudomonas aeruginosa sepsis. Arteritis of the renal artery in both patients was caused by C. albicans. This was confirmed by histopathology: infiltration of renal artery with budding yeast forming pseudohyphae (Case 1), and the presence of C. albicans in the culture of the renal artery and surrounding tissue (Case 2). We conclude that organ preservation solution should be cultured with use of media selective for fungal growth. As soon as the positive culture is detected, appropriate measures protecting patients against CAA should be undertaken.

1

Solid organ transplantation recipients are at risk for invasive fungal infections. Candida and Aspergillus species were reported as the most common fungal pathogens associated with invasive disease in organ recipients at 59.0% and 24.8%, respectively (1, 2). One of

Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland, 2 Department of Transplantation Medicine and Nephrology, Transplantation Institute, Medical University of Warsaw, Warszawa, Poland, 3Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Gdansk, Poland, 4Department of Clinical Microbiology, University Clinical Center of Gdansk, Gdansk, Poland

Key words: renal transplant; infection; arteritis; Candida albicans; mycotic arteritis Correspondence to: Alicja Dez bska-Slizien, Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, ul. Dez binki 7, Gdansk 80-952, Poland Tel: +48 58 349 25 58 Fax: +48 58 349 25 51 E-mail: [email protected]

Received 29 December 2014, revised 12 March 2015, accepted for publication 20 March 2015 DOI: 10.1111/tid.12388 Transpl Infect Dis 2015: 17: 449–455

the life-threatening forms of invasive fungal infection in renal transplant recipients is mycotic arteritis. Candida albicans and (rarely) Aspergillus cause mycotic arteritis, which compromises the renal graft anastomosis (3, 4). This complication is rare (1 case per 1000 grafts), but

449

 Dez bska-Slizie n et al: Candida arteritis in renal transplants

7. Laouad M, Buchler C, Noel C, et al. Renal artery aneurysm secondary to Candida albicans in four kidney allograft recipients. Transplant Proc 2005; 37: 2834–2836. 8. Zeller V, Lortholary O. Vasculitis secondary to fungal infections. Presse Med 2004; 33: 1385–1388. 9. Nyberg SL, Baskin-Bey ES, Kremers W, et al. Improving the protection of donor kidney quality: deceased donor score and resistive indices. Transplantation 2005; 80: 925–929. 10. Kountidou CS, Stier K, Niehues SM, et al. Successful repair of posttransplant mycotic aneurysm of iliac artery with renal graft preservation: a case report. Urology 2012; 80: 1151–1153.

11. Battaglia M, Ditonno P, Fiore T, et al. True mycotic arteritis by Candida albicans in 2 kidney transplant recipients from the same donor. J Urol 2000; 163 (4): 1236–1237. 12. Zibari GB, Lipka J, Zizzi H, Abreo KD, Jacobbi L, McDonald JC. The use of contaminated donor organs in transplantation. Clin Transplant 2000; 14: 397–400. 13. Sanchez AA, Johnston DA, Myers C, et al. Relationship between Candida albicans virulence during experimental hematogenously disseminated infection and endothelial cell damage in vitro. Infect Immun 2004; 72 (1): 598–601.

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Candida arteritis in kidney transplant recipients: case report and review of the literature.

Multi-organ procurement is a risk factor for contamination of preservation fluid with intestinal flora including fungi (e.g., Candida). Transmission o...
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