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  Table of Contents    
CASE REPORT  
Year : 2012  |  Volume : 55  |  Issue : 4  |  Page : 580-582
Progression of hepatic aspergillosis following second renal transplantation in a patient with recurrent glomerulonephritis


1 Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

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Date of Web Publication4-Mar-2013
 

   Abstract 

Invasive aspergillosis is a serious complication in renal transplant recipients. Hepatic involvement, although seen in liver transplant recipients, has not been reported following renal transplantation. We describe here an interesting occurrence of hepatic Aspergillus infection in a renal transplant recipient. The infection responded to anti-fungal therapy, but there was re-activation following a second renal transplant. In addition, the patient had recurrence of the underlying membrano-proliferative glomerulonephritis following both transplants. The relevant existing literature relating to these problems has been reviewed.

Keywords: Aspergillosis, hepatic abscess, recurrent glomerulonephritis, renal transplantation

How to cite this article:
Gupta KL, Rajaram K G, Joshi K, Sakhuja V. Progression of hepatic aspergillosis following second renal transplantation in a patient with recurrent glomerulonephritis. Indian J Pathol Microbiol 2012;55:580-2

How to cite this URL:
Gupta KL, Rajaram K G, Joshi K, Sakhuja V. Progression of hepatic aspergillosis following second renal transplantation in a patient with recurrent glomerulonephritis. Indian J Pathol Microbiol [serial online] 2012 [cited 2019 Nov 14];55:580-2. Available from: http://www.ijpmonline.org/text.asp?2012/55/4/580/107831



   Introduction Top


Invasive aspergillosis occurs mostly in immuno-compromised patients, and its incidence in renal transplant recipients is 0.7%. [1],[2] Most cases present with pulmonary aspergillosis, and some may have disseminated disease. Liver involvement in invasive aspergillosis is sometimes seen, but isolated hepatic aspergillosis is rarely seen in immune deficiency and after liver transplantation but has never been reported in renal transplant recipients. [3],[4]

Recurrent glomerular disease is well described following renal transplantation, and membrano-proliferative glomerulonephritis (MPGN) may recur depending upon the type and severity of the original disease. [5],[6]

We describe here an unusual case of a renal transplant recipient who developed recurrent MPGN type I following two consecutive renal transplants. He developed a relapse of an indolent and appropriately-treated Aspergillus hepatic abscess after the second renal transplant. This is the first such case to be reported in the literature of such an occurrence.


   Case Report Top


A 37-year-old male presented to our renal clinic with end-stage renal disease, for which he was initiated on maintenance hemodialysis. He had a 2-year history of renal biopsy-proven MPGN, at which time his serum creatinine was 4 mg/dL. He underwent a living donor renal transplant 18 months ago, the donor being his sister. He was administered triple-drug immunosuppressive therapy (cyclosporine [CSA], azathioprine [AZA] and prednisolone [Pred]). In the early post-transplant period, the patient had one episode of acute rejection, which responded to pulse methyprednisolone therapy.

One and a half year following renal transplantation, the patient developed anasarca, microhematuria, and deterioration in graft function (serum creatinine of 5.1 mg/dL). Graft biopsy revealed features of recurrent MPGN type I on the basis of light microscopy (LM) and immunofluorescence (IMF) with IgG and C3 deposits in the mesangium. During this time, he also developed a high-grade fever of 3 weeks duration with associated breathlessness. Laboratory investigation revealed a hemoglobin of 6.5 gm/dL, a total leukocyte count of 20,200/cmm with 84% polymorphs, and normal liver function tests. Tests for cytomegalovirus antigen (CMV), hepatitis B surface antigen (HbsAg), and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (HIV) were negative. Blood and urine cultures were sterile. Chest x-ray was suggestive of bronchopneumonia. Initially, the patient was treated empirically with broad-spectrum antibiotics and subsequently with anti-tubercular therapy, to which we observed no response. Detailed evaluation of the abdomen by ultrasound and later by computerized tomography (CT) revealed an abscess in the liver [Figure 1] with encysted ascites and peri-splenic collection of fluid. Ultrasound-guided catheter drainage of the liver abscess cavity was performed. A smear prepared from the aspirated pus showed dichotomously branching septate fungal filaments consistent with Aspergillus spp. A test for Aspergillus with the galactomannan antigen was also positive. In view of the presence of invasive fungal infection, immunosuppression was withdrawn and the patient treated with a cumulative dose of 2.3 grams of amphotericin B followed by maintenance itraconozole 200 mg twice daily for one year. The infection responded to the medication as evidenced by the disappearance of intra-abdominal collections of fluid and a decrease in the size of the abscess cavity in the liver. A repeat aspiration from the cavity did not reveal any organisms.
Figure 1: CECT abdomen showing an aspergilloma of liver (arrow)

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Meanwhile, the graft function deteriorated, and patient was maintained on hemodialysis for one year. He underwent a second renal transplantation; the donor this time was his wife. The immunosuppression again consisted of CSA, AZA, and Pred. He remained asymptomatic with a serum creatinine of 1.1 mg/dl. Six weeks after transplantation, a routine ultrasound detected echogenic material within the liver cavity, which had increased in size, and the aspiration smear was again suggestive of Aspergillus infection. Surgical debridement of the hepatic abscess was carried out. Histopathology of the excised liver tissue showed evidence of chronic granulomatous invasive aspergillosis with central necrosis surrounded by fibrosis and chronic inflammation including scattered giant cells [Figure 2]. Another histological section showed an active hepatic abscess with acute inflammatory cells and giant cells having negative profiles of fungal hyphae consistent with Aspergillus. The organisms were better appreciated with Grocott's methenamine silver stain [Figure 3]. The patient received a total of 2.4 gm of amphotericin-B deoxycholate followed by itraconazole.
Figure 2: Photomicrograph of chronic hepatic aspergilloma with central necrosis surrounded by few Giant cells (arrows) and fibrotic wall (HE ×125)

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Figure 3: Photomicrograph of an active hepatic abscess showing giant cells with negative profiles of fungal hyphae (arrows) surrounded by inflammatory cells ( PAS × 325). INSET: Dichotomously branching septate fungal hyphae of aspergillus ( Groccot stain × 550)

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Six months following the second transplant, the patient was admitted with edema, proteinuria of 2.6 gms/day, microhematuria, and a serum creatinine of 2.1 mg/dL. A biopsy of the graft revealed features of recurrent type I MPGN on LM and IMF. After a 2-year follow-up, there was no relapse of the fungal infection. Also, the graft function deteriorated with an increase in serum creatinine to 6 mg/L, and the patient died of septicemia.


   Discussion Top


Aspergillus species are soil-dwelling organisms that contribute to the decay of organic debris and are widely distributed in nature. They can cause serious infection in immune-compromised patients including solid organ transplant recipients. [1],[2] Major clinical syndromes include allergic aspergillosis, aspergilloma and invasive disease, which carries a high morbidity and mortality in renal transplant recipients. Its incidence reported as 4% in earlier studies has decreased to 0.7% in recent studies. [2] Renal transplant recipients have a higher risk for invasive disease during first 6 months after transplantation. This is attributed to the frequent use of high-dose corticosteroid therapy for treatment of acute rejection.

With invasive aspergillosis, the brain is the commonest extra-pulmonary site to be affected in disseminated disease. Liver involvement as a predominant manifestation is very rare in immunocompromised patients including those with immunodeficiency syndrome, malignancy, and following liver transplantation. [1],[2],[3],[4],[7] In an autopsy study of 93 neoplastic patients with aspergillosis, only 5 patients had liver involvement. [7] Among the 5 patients, 3 had a solitary abscess, 1 had multiple abscesses, and 1 patient had a nodule of hemorrhagic necrosis.

In solid organ transplants also, there have been occasional reports of isolated hepatic aspergillosis in liver transplant recipients. Mazza et al.[4] described the first case of successful management of an Aspergillus liver abscess in a liver transplant recipient. To the best of our knowledge, no case of isolated hepatic abscess in a renal transplant recipient has been reported so far. Another unique finding in our patient was that of relapse of chronic hepatic aspergillosis with active abscess soon after heavy immunosuppression for the second transplant. Such worsening has also been described by Van Der Velden et al. [8] who documented progression of primary hepatic invasive aspergillosis following anti-CD20 treatment with rituximab. Their patient developed post-transplantation lymphoproliferative disease following allogeneic stem cell transplantation.

Our patient also had recurrence of MPGN in both the allografts. Recurrence of MPGN depends upon the type and severity of the original disease. Type II MPGN is reported to recur in up to 90% of transplant recipients with a worse outcome, and type I MPGN recurs in 29-33% though some authors have reported the recurrence as high as 80%. [9] These patients often have marked proteinuria and/or elevated serum creatinine levels. Graft loss is higher (up to 40%) in patients with recurrent MPGN than in those without recurrent MPGN, and the risk of recurrence in subsequent grafts approaches 80%, particularly in those having a live donor transplant as happened in our case. [10]

To conclude, our patient developed relapse of aspergillosis in the liver following second renal transplantation with evidence of invasion, probably due to re-introduction of immunosuppression. Surgical debridement along with antifungal therapy helped in eradicating the fungus. Recurrence of MPGN also contributed to graft loss and associated morbidity in this patient. This is probably the first such case to the best of our knowledge.

 
   References Top

1.Bhatti Z, Shaukat A, Almyroudis NG, Segal BH. Review of epidemiology, diagnosis, and treatment of invasive mould infections in allogeneic hematopoietic stem cell transplant recipients. Mycopathologia 2006;162:1-15.  Back to cited text no. 1
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2.Singh N, Paterson DL. Aspergillus Infections in Transplant Recipients. Clin Microbiol Rev 2005;18:44-69.  Back to cited text no. 2
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3.Mamishi S, Zomorodian K, Saadat F, Gerami-Shoar M, Tarazooie B, Siadati SA. A case of invasive aspergillosis in CGD patient successfully treated with Amphotericin B and INF-gamma. Ann Clin Microbiol Antimicrob 2005;4;4.  Back to cited text no. 3
    
4.Mazza D, Gugenheim J, Toouli J, Moniel J. Survivial of a liver graft recipient treated for an aspergillar liver abscess. Clin Infect Dis 1996;23:831-2.  Back to cited text no. 4
    
5.Chadban S. Glomerulonephritis Recurrence in the Renal Graft. J Am Soc Nephrol 2001;12:394-402.  Back to cited text no. 5
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6.Glicklich D, Matas AJ, Sablay LB, Senitzer D, Tellis VA, Soberman R, et al. Recurrent membranoproliferative glomerulonephritis type 1 in successive renal transplants. Am J Nephrol 1987;7:143-9.  Back to cited text no. 6
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7.Meyer RD, Young LS, Armstrong D, Yu B. Aspergillosis complicating neoplastic disease. Am J Med 1973;54:6-15.  Back to cited text no. 7
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8.van der Velden WJ, Blijlevens NM, Klont RR, Donnelly JP, Verweij PE. Primary hepatic invasive aspergillosis with progression after rituximab therapy for a post transplantation lymphoproliferative disorder. Ann Hematol 2006;85:621-3.  Back to cited text no. 8
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9.Ramos EL, Tisher CC. Recurrent diseases in the kidney transplant. Am J Kidney Dis 1994;24:142-54.  Back to cited text no. 9
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10.Andresdottir MB, Assmann KJ, Hoitsma AJ, Koene RA, Wetzels JF. Recurrence of type 1 membranoproliferative glomerulonephritis after renal transplantation: Analysis of the incidence, risk factors, and impact on graft survival. Transplantation 1997;63:1628-33.  Back to cited text no. 10
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Correspondence Address:
Krishan L Gupta
Department Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.107831

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