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Table of Contents
CASE REPORT
Year : 2018  |  Volume : 12  |  Issue : 3  |  Page : 216-218

Postrenal transplant dual viral infection: A double jeopardy


Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India

Date of Web Publication28-Sep-2018

Correspondence Address:
Dr. Avinash Rao
Department of Nephrology, Muljibhai Patel Urological Hospital, Dr. Virendra Desai Road, Nadiad . 387 001, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_27_18

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  Abstract 


Despite significant advances in the field of renal transplantation, long-term graft survival has not dramatically increased. The reasons for this are varied but include the persistent impact of infectious diseases on transplant recipients. Viral infections continue to be a potential contributor to graft failure, but also a cause of severe mortality and morbidity. We hereby present a case of early posttransplant dual viral infection detected and treated during the initial 2 months and discuss the risk factors which were involved, potential preventive strategies and therapies that could be helpful in treating such patients.

Keywords: Cytomegalovirus, parvovirus, transplantation


How to cite this article:
Rao A, Konnur A, Gang S. Postrenal transplant dual viral infection: A double jeopardy. Indian J Transplant 2018;12:216-8

How to cite this URL:
Rao A, Konnur A, Gang S. Postrenal transplant dual viral infection: A double jeopardy. Indian J Transplant [serial online] 2018 [cited 2018 Dec 11];12:216-8. Available from: http://www.ijtonline.in/text.asp?2018/12/3/216/242430




  Introduction Top


Viral infections are common in renal transplant recipients predisposed by the immunosuppression needed to maintain the graft function. Simultaneous infections with two different viruses would lead to serious morbidity in these patients and requires urgent diagnosis and management.


  Case Report Top


A 32 year gentleman with no previous co morbidities, was diagnosed with end stage renal disease of undetermined etiology in August 2017. He was initiated on maintenance hemodialysis thrice per week since then. He was transfused with two units of packed red cells in view of severe iron deficiency anemia. Renal transplantation was planned with father as the donor. The patient had intermittent fever and weight loss on hemodialysis. On evaluation, noncontrast computed tomography abdomen showed multiple enlarged, conglomerated, and necrotic abdominal and retroperitoneal lymph nodes with mild hepatosplenomegaly with multiple nonenhancing hypodense lesions suggestive of tubercular etiology. He was started on anti-tubercular therapy (isoniazid, rifampicin, pyrazinamide, and ethambutol with renal modification). The patient persisted to have a fever for 1 month after being on anti-tubercular treatment (ATT). His complete hemogram showed hemoglobin of 8.4 g/dL with normal total leukocyte count and platelet count. Laparoscopic lymph node excision biopsy was done to confirm the etiology. Histopathology of lymph node was showing necrotizing granulomatous changes. Hence, he was continued on ATT and fever gradually subsided. He was evaluated for renal transplantation. His pretransplant recipient status during evaluation showed serology being negative for HIV, hepatitis B, and hepatitis C. He had IgG antibodies positive for Cytomegalovirus (CMV) as well as Epstein-Barr virus (EBV) (R+). The donor was 61 years male, chronic smoker, with no previous comorbidities, also was seronegative for HIV, hepatitis B, and hepatitis C. He also had IgG antibodies positive for CMV as well as EBV (D+). The patient underwent uneventful renal transplant on December 28, 2017. Basiliximab was used for induction in view of prior sensitization with blood transfusion, and maintenance immunosuppression was with oral prednisolone, tacrolimus, and mycophenolate mofetil (MMF). There was no postoperative complication. The patient was discharged on day 9 with serum creatinine of 0.72 mg/dl. Postrenal transplantation, his hemoglobin remained around 9–10 g/dL. His renal function and liver function parameters were normal. After 2 months of follow-up, he presented in the outpatient department with generalized weakness and high-grade fever for 3 days. He had no associated dysuria/flank pain/decreased urine output/joint pain/cough/rashes/vomiting/loose stools. He was admitted for evaluation.

On the day of admission, he was febrile with a temperature of 103° F. He had pallor on examination. His systemic examination was normal. His laboratory examination on the day of admission showed the following reports. He had anemia with hemoglobin of 5.9 g/dl with normal platelets and leukocyte count. Peripheral smear showed normocytic and normochromic picture with no evidence of hemolysis. He had normal iron studies. His stool was examined for occult blood which was negative. Reticulocyte count was low with a value of <0.5%. Renal function tests were normal. Liver function tests were normal. Urine complete examination was normal. Blood culture was sterile. In view of persistent anemia, qualitative real-time polymerase chain reaction (PCR) for parvovirus was sent which was found to be detected. Bone marrow examination was also done which showed hypocellular marrow with erythroid hypoplasia, but no inclusion bodies were detected. The patient was transfused with 2 units of leukocyte depleted blood and intravenous (IV) immunoglobulin was given at a dose of 400 mg/kg for 5 days. On regular monitoring, after 1 week of therapy, his platelets counts started decreasing, and there was increase in serum creatinine to 1.7 mg/dL and platelet count dropped to 90,000/cumm. In view of associated infections, his CMV DNA PCR was sent, which came to be detected with a count of 4.5 lakh copies/ml. The MMF was withdrawn from the immunosuppression maintenance regime. He was then put on injectable ganciclovir therapy with a dose of 5 mg/kg 12 hourly for next 21 days, and his CMV DNA levels were monitored weekly. Qualitative PCR for parvovirus was repeated every weekly which became negative after 1 month. CMV DNA PCR came to be negative after 3 weeks of treatment. His blood counts and renal functions improved gradually. The MMF was restarted with a lower dose and then gradually increased. He was continued on oral valganciclovir 900 mg OD for the next 3 months.


  Discussion Top


Even though renal transplantation has been considered as a superior treatment in management of chronic kidney disease patients, significant proportion of renal transplant recipients suffer from various morbidities. As per USRDS data, the probability of death by 10th year posttransplant is around 8% in comparison to Indian data of 17%.[1],[2] Around 10% of the renal transplant recipients have graft failure secondary to the viral infections.[3]

CMV and parvovirus are ubiquitous organisms prevalent in the environment. CMV infection is present in the general population to the extent of 60%–80%, with detectable levels in renal transplant recipients and donors before the transplant although not manifesting clinically.[4] Risk factors for the development of CMV in the transplant scenario include donor seropositivity (especially if the recipient is seronegative), use of induction immunosuppression (T-cell depleting antibodies), simultaneous kidney-pancreas transplantation, older donors (>60 years), presence of allograft rejection, and concurrent infection from other viruses. Antilymphocyte antibody is associated with a 2-5 fold increase in the rate of CMV.[5],[6]

Parvovirus infection is acquired in the childhood and 70%–85% of adults show serologic evidence of the past infection.[7],[8] Transmission of the virus usually occurs through aerosol spread and can also be transmitted from mother to fetus vertically.[9] Parvovirus causes several clinical manifestations including fifth disease, transient aplastic crisis, pure red cell aplasia, and hydrops fetalis depending on the age and immunity of the patient.

Transplant recipients are at the greatest risk for the CMV-related diseases in view of immunosuppression. Among the solid organ transplants, kidney transplant carries a lower risk of CMV infection as compared to lung and small bowel transplants.[10],[11] Although innate and adaptive host immune defects, age and underlying comorbidities may play a role in the occurrence of the CMV disease postrenal transplant, the CMV serostatus of the donor and the recipient pre-transplant is the most important factor.[12] In one of the Indian studies, among 521 living donor renal transplant patients, the incidence of CMV disease posttransplant was 14.2% at a median follow-up period of 7.18 ± 4.35 months from transplantation.[13]

The most common manifestation of the parvovirus infection in the transplant recipients is pure red cell aplasia and other cytopenias. Very rare cases of collapsing glomerulopathy and thrombotic microangiopathy have been reported, but the causal relationship still needs to be explored. Transplant patients may get infected through the aerosol route, from the donor organ or the reactivation of the latent infection.[14]

The CMV infections in the transplant patients should be suspected who present with the symptoms such as nausea, vomiting, abdominal pain, cough, shortness of breath, headache, nuchal rigidity, mental changes, or laboratory features suggestive such as transaminitis or asymptomatic increase in serum creatinine. Confirmation of the infection can be done using nucleic acid testing for the CMV DNA levels in blood, cerebrospinal fluid or vitreal fluid.[11] Histopathologic examination of the graft biopsy specimen could be used to detect the infection which is typically dictated by the presence of cellular and nuclear enlargement and the presence of the amphophilic or basophilic cytoplasmic inclusions, which represent aggregates of CMV nucleoproteins.[15]

At our center, the treatment of the CMV infection is done when the patient presents with the clinical signs and symptoms suggestive of the infections and CMV DNA PCR levels exceed >2000 copies/ml or the graft biopsy specimen examination is consistent with the infection. As practiced in many other different centers, we generally withdraw the antimetabolite from the immunosuppression regime and start on the antiviral therapy, i.e., IV ganciclovir 5 mg/kg every 12 hourly for 21 days and then continue on oral valganciclovir 900 mg OD for the next 3 months. We monitor the blood counts every weekly in these patients during follow-up as these drugs are well known to cause hematologic suppression.

The parvovirus infection is usually tackled with the transfusion of the leukocyte depleted irradiated packed cells if the hemoglobin drops to <6 g/dL and IV immunoglobulin with a dose of 400 mg/kg at least for 5 days. Otherwise, a careful wait and watch technique would be sufficient as the viral infection is usually transient and resolves on its own.

The case has been presented after taking the informed consent. This paper is interesting because of the presence of the dual viral infection presenting in the same patient. The several thoughts that come to light in this context are (1) whether infection with one virus predisposes for the occurrence of the other? (2) Whether the blood transfusion given in this patient led to the occurrence of the CMV infection even though it was leukocyte depleted and irradiated? (3) Whether all the immunosuppressed patients need to evaluate for the presence of other viral etiology in the presence of one? (4) Whether the pretransplant blood transfusions lead to the increased occurrence of these infections when immunosuppressed? These thoughts need to be analyzed in the future studies on the viral infections in this group of patients.


  Conclusion Top


This is one of the very few papers in the literature reporting dual viral infections occurring concurrently in a renal transplant recipient. These infections, when treated timely, would save the graft in effective manner. Few questions that arose during the discussion in the present paper need to be answered in the future studies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
USRDS annual data report. ESRD in United States. 2015;7:227-38.  Back to cited text no. 1
    
2.
Mukhopadhyay P, Gupta KL, Kumar V, Ramachandran R, Rathi M, Sharma A,et al. Predictors of allograft survival and patient survival in living donor renal transplant recipients. Indian J Transplat 2017;11:42-8.  Back to cited text no. 2
    
3.
Hibberd PL, Rubin RH. Renal transplantation and related infections. Semin Respir Infect 1993;8:216-24.  Back to cited text no. 3
    
4.
Brennan DC. Cytomegalovirus in renal transplantation. J Am Soc Nephrol 2001;12:848-55.  Back to cited text no. 4
    
5.
De Keyzer K, Van Laecke S, Peeters P, Vanholder R. Human Cytomegalovirus and kidney transplantation: A clinician's update. Am J Kidney Dis 2011;58:118-26.  Back to cited text no. 5
    
6.
San Juan R, Aguado JM, Lumbreras C, Fortun J, Muñoz P, Gavalda J,et al. Impact of current transplantation management on the development of Cytomegalovirus disease after renal transplantation. Clin Infect Dis 2008;47:875-82.  Back to cited text no. 6
    
7.
Kelly HA, Siebert D, Hammond R, Leydon J, Kiely P, Maskill W. The age-specific prevalence of human parvovirus immunity in victoria, Australia compared with other parts of the world. Epidemiol Infect 2000;124:449-57.  Back to cited text no. 7
    
8.
Cohen BJ, Buckley MM. The prevalence of antibody to human parvovirus B19 in England and wales. J Med Microbiol 1988;25:151-3.  Back to cited text no. 8
    
9.
Jordan JA. Identification of human parvovirus B19 infection in idiopathic nonimmune hydrops fetalis. Am J Obstet Gynecol 1996;174:37-42.  Back to cited text no. 9
    
10.
Gordon CR, Avery RK, Abouhassan W, Siemionow M. Cytomegalovirus and other infectious issues related to face transplantation: Specific considerations, lessons learned, and future recommendations. Plast Reconstr Surg 2011;127:1515-23.  Back to cited text no. 10
    
11.
Razonable RR, Humar A; AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplantation. Am J Transplant 2013;13 Suppl 4:93-106.  Back to cited text no. 11
    
12.
Schnitzler MA, Woodward RS, Brennan DC, Spitznagel EL, Dunagan WC, Bailey TC. Impact of Cytomegalovirus serology on graft survival in living related kidney transplantation: Implications for donor selection. Surgery 1997;121:563-8.  Back to cited text no. 12
    
13.
Bhadauria D, Sharma RK, Kaul A, Prasad N, Gupta A, Gupta A. Cytomegalovirus disease in renal transplant recipients: A single-center experience. Indian J Microbiol 2012;52:510-5.  Back to cited text no. 13
    
14.
Waldman M, Kopp JB. Parvovirus-B19-associated complications in renal transplant recipients. Nat Clin Pract Nephrol 2007;3:540-50.  Back to cited text no. 14
    
15.
Mattes FM, McLaughlin JE, Emery VC, Clark DA, Griffiths PD. Histopathological detection of owl's eye inclusions is still specific for Cytomegalovirus in the era of human herpesviruses 6 and 7. J Clin Pathol 2000;53:612-4.  Back to cited text no. 15
    




 

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