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Year : 2018  |  Volume : 12  |  Issue : 4  |  Page : 233-235

Viral nephropathies in renal transplantation with a special emphasis on adenovirus infection

Department of Nephrology and Renal Transplantation, Asian Institute of Nephrology and Urology, Hyderabad, Telangana, India

Date of Web Publication18-Dec-2018

Correspondence Address:
Dr. Praveen Kumar Etta
Department of Nephrology and Renal Transplantation, Asian Institute of Nephrology and Urology, Hyderabad, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_38_18

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How to cite this article:
Etta PK. Viral nephropathies in renal transplantation with a special emphasis on adenovirus infection. Indian J Transplant 2018;12:233-5

How to cite this URL:
Etta PK. Viral nephropathies in renal transplantation with a special emphasis on adenovirus infection. Indian J Transplant [serial online] 2018 [cited 2021 Apr 11];12:233-5. Available from: https://www.ijtonline.in/text.asp?2018/12/4/233/247792

Dear Colleagues,

Allograft nephropathy from a viral infection is an evolving challenge in renal transplant (RT) recipients. It is commonly the consequence of potent immunosuppression aimed at reducing rejection and improving graft survival. Untreated viral infection may lead to graft dysfunction or loss. Although decreased immunosuppression is the principle treatment in majority of these infections, graft failure is commonly encountered in advanced cases.

Most common type of viral nephropathy in RT recipients is due to polyomavirus infection. The three known human polyomaviruses include BK virus (BKV), JC virus, and Simian Virus 40. BKV is by far the most common polyomavirus that causes kidney disease. Other viral nephropathies are due to cytomegalovirus, adenovirus (AdV), Epstein–Barr virus, less commonly hepatitis A, B, and C, human immunodeficiency virus, parvovirus B19, hantavirus, dengue, mumps, and measles.

Viral nephropathies can present with glomerular disease, tubulointerstitial disease, vasculitis, and other renal and extrarenal manifestations. The pathogenesis and mechanisms of virus-induced renal injury include:[1],[2]

  1. Direct cytopathic effect of virus and its antigens
  2. Host inflammatory response: Cytokines, chemokines, adhesion molecules, necrosis, apoptosis, altered matrix synthesis, and degradation
  3. In situ immune complex formation: Host antibody binding to viral antigens that are bound to glomerular structures
  4. Circulating immune complexes formed by viral antigens and host antiviral antibodies
  5. Autoantibodies directed against host antigens modified by viral injury.

A direct causative relationship between a virus and a specific kidney disease is often difficult to establish. This usually involves demonstration of viral antigens and host antibodies in blood and/or kidney tissue. In this commentary, AdV infection followed by comparison of common types of viral nephropathies in renal transplantation will be addressed.

  Adenovirus Infection Top

AdVs are nonenveloped, double-stranded DNA viruses that usually cause self-limiting infections but have the potential to cause fatal infections in immunocompromised hosts including transplant recipients. Majority of AdV infections have been reported among stem cell transplant recipients. The incidence of AdV infections in solid-organ transplantation depends not only on level of immunosuppression but also the organ transplanted; infections were reported more commonly in children, and lung and liver transplant (LT) recipients. On the contrary, in RT recipients, the majority of infections have been reported in adults, with the incidence of up to 4%.[3]

Interestingly, AdV disease typically involves the donor organ (allograft) in solid organ transplant recipients. Hence, clinical features vary with the organ transplanted. The two most common presentations in RT recipients include hemorrhagic cystitis and tubulointerstitial nephritis (TIN). Less commonly, they can also manifest as hepatitis, gastroenteritis, pneumonia, orchitis, or disseminated disease. The most prevalent AdV subgroups are B1 and B2 with the serotypes 7, 11, 34, and 35. The incubation period is up to 2-week duration. Disease can occur both due to de novo infection and viral reactivation. Most infections occur in the 1st year after transplantation. One study reported that >75% of infections were diagnosed within 3 months of transplantation.[3]

Viral culture, direct antigen detection, molecular methods, and histopathology are the most commonly used diagnostic tests. Serologic testing is not frequently used due to poor sensitivity. Viral culture has limited clinical use as it may take few weeks for the result. Amplification and detection of viral genome by either qualitative or quantitative polymerase chain reaction (PCR) is the most commonly used diagnostic test. It is highly sensitive, provides relatively rapid results and can detect all AdV serotypes. Isolation of virus by culture or PCR does not necessarily correlate with the clinical diagnosis as virus can be asymptomatically shed for prolonged periods of time. They should be correlated with the clinical presentation and histopathology to differentiate disease from asymptomatic shedding.

The prevalence of asymptomatic viremia in RT recipients is common (6%–7%), but the risk of progression to AdV disease remains unknown. Hence, routine screening for viremia is not recommended currently. In a study published in this issue, the authors have retrospectively assessed incidence of AdV infection in LT and RT recipients by testing blood samples collected within 100 days of transplantation for AdV DNA by real-time PCR assay. Around 150 patients –129 LT and 21 RT recipients were tested and AdV was not detected in any of the samples. The authors opined that the retrospective nature of the study comprising mostly adult population might have affected the results.[4]

Renal biopsy typically shows features of TIN with normal glomeruli and blood vessels. Viral cytopathic effects such as nuclear enlargement, peripheral condensation of chromatin, and basophilic intranuclear viral inclusions are seen in tubular epithelial cells. Sometimes, it can present with granuloma formation. Presence of virus within the tissue can be confirmed using immunoperoxidase staining or in situ hybridization. Electron microscopy shows the typical 70–80 nm diameter viral particles within the nuclei and cytoplasm of tubular epithelial cells. AdV nephropathy can be mistaken for rejection or other viral infections [Table 1].[5] Sometimes, both infection and rejection can coexist and it is very difficult to manage them.
Table 1: Viral nephropathies in renal transplant

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In most of the cases, reduction of immunosuppression leads to resolution of disease. The role of antiviral agents in kidney transplantation is not well studied. They may be useful in early-onset disease, especially in patients with pneumonia, enteritis, hepatitis, and in cases of progressive disease despite immunosuppression reduction. Till date, there are no prospective randomized clinical trials available to support the use of these drugs. Cidofovir is the most commonly used antiviral agent, and it needs dose modification in renal impairment.[6] Probenecid along with hydration helps in reducing the nephrotoxicity of cidofovir. Brincidofovir (lipid conjugate of cidofovir) is nonnephrotoxic and might be more effective as it achieves much higher intracellular levels of active drug than cidofovir.[7] Intravenous immunoglobulin, ganciclovir, and ribavirin have been tried in few cases with limited efficacy.

  References Top

Faulhaber JR, Nelson PJ. Virus-induced cellular immune mechanisms of injury to the kidney. Clin J Am Soc Nephrol 2007;2 Suppl 1:S2-5.  Back to cited text no. 1
Alpers CE, Kowalewska J. Emerging paradigms in the renal pathology of viral diseases. Clin J Am Soc Nephrol 2007;2 Suppl 1:S6-12.  Back to cited text no. 2
Watcharananan SP, Avery R, Ingsathit A, Malathum K, Chantratita W, Mavichak V, et al. Adenovirus disease after kidney transplantation: Course of infection and outcome in relation to blood viral load and immune recovery. Am J Transplant 2011;11:1308-14.  Back to cited text no. 3
Lall S, Gupta E, Lata S, Khanna R, Pamecha V. Adenovirus infections in solid-organ transplant recipients: An observational study from a tertiary care center. Indian J Transplant 2018;12:230-1.  Back to cited text no. 4
  [Full text]  
Storsley L, Gibson IW. Adenovirus interstitial nephritis and rejection in an allograft. J Am Soc Nephrol 2011;22:1423-7.  Back to cited text no. 5
Lenaerts L, Naesens L. Antiviral therapy for adenovirus infections. Antiviral Res 2006;71:172-80.  Back to cited text no. 6
Painter W, Robertson A, Trost LC, Godkin S, Lampert B, Painter G, et al. First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Antimicrob Agents Chemother 2012;56:2726-34.  Back to cited text no. 7


  [Table 1]

This article has been cited by
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PraveenKumar Etta,Thatipamula Madhavi,Swarnalata Gowrishankar
Indian Journal of Transplantation. 2020; 14(2): 147
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4 Granulomatous interstitial nephritis in native kidneys and renal allografts
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