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 Infectious Disease Online

Did you have a kidney transplant?

Beware of these top 4 Viral Infectious Diseases.

 Dr Sampurna Roy MD  




Renal Transplant Pathology:

Renal transplantation is the treatment of choice for majority of patients suffering end stage renal failure.

The renal transplant biopsy plays a central role in the diagnosis of renal allograft dysfunction.

It is particularly important in differentiating immune-mediated rejection from various infective, ischaemic and toxic pathologies. Viruses are the most common causes of opportunistic infection after transplantation.

In the early post-transplant period, renal function is monitored on a daily basis by measurement of serum creatinine. Later, when renal function remains normal creatinine is measured less frequently.

The renal biopsy is one of a number of investigations carried out for the monitoring of a rising serum creatinine. Other investigations include the monitoring of the levels of immunosuppressive drugs, urine microbiology, renal ultrasound to detect obstruction of the urinary tract, radio-isotope studies to detect changes in renal uptake or focal lesions and virological studies to detect infections.


Viral Infections in Transplant Kidney:

According to Jovana Cukuranovic et al:

 "Epidemiologically, some viral infections are the result of community exposures (influenza, adenovirus), whereas some are commonly transmitted with the allograft (cytomegalovirus, Epstein-Barr virus), and others are the result of more distant exposures reactivated in the setting of immune suppression (chicken pox and varicella zoster as shingles). Multiple simultaneous infections, viral and nonviral, are also common, such as cytomegalovirus and human herpes virus 6 or cytomegalovirus and pneumocystis."

Viral Infection in Renal Transplant Recipients


Top 4 Viral Infections in Transplant Kidney:


1. Human Polyoma Virus :

- This family of viruses include JC virus and BK virus (BKV).

- It is BKV that, after primary infection, remain latent in the renal tubular epithelium.

- Re-activation occurs in the renal allograft as a result of immunosuppression.

- The peak incidence of Polyoma Virus infection is in the first 6 months post-transplantation, but infection may persist for months or even years.

- Histologically, infection causes a tubulointerstitial nephritis that may mimic acute tubulointerstitial rejection (AIR).

- Plasma cells are often prominent within the interstitial infiltrate.

- The degree of tubular injury is is usually out of proportion to the severity of tubulitis.

- The epithelial cell nuclei show characteristic nuclear enlargement with smudged chromatin and basophilic viral inclusions.

- Polyoma Virus infection can be confirmed with immunohistochemistry for SV40, which cross reacts with BKV,  in situ hybridisation and electron microscopy.

- Electron microscopy shows lattice-like aggregates of the 40-45 nm diameter spherical virions.

- Polyoma Virus infected cells, can also be detected in the urine and urine cytology is a sensitive non-invasive method for detecting clinically significant infection.

- Polyoma virus infection usually respond to a reduction in immunosuppression but persistent viruria is associated with progressive graft dysfunction and the development of chronic allograft nephropathy (CAN).

2. Epstein-Barr Virus associated post-transplant lymphoproliferative disease (PTLD) : 

Visit: Epstein-Barr Virus Related Malignant Tumours

Visit: Epstein-Barr Virus infection

- Epstein-Barr Virus associated PTLD occurs in around 2% of renal transplant recipients.

- Destructive polymorphic lesions and monomorphic lesions, usually resembling high grade lymphoma, are extranodal in over 50% of cases and usually show multiorgan involvement.

- The transplant kidney is commonly involved and the renal infiltrate may mimic rejection, with tubulitis and even arteritis.

- Features at light microscopy that suggest (PTLD) include expansile destructive infiltrates, containing areas of necrosis.

- Immunohistochemistry for CD20 and CD3 will differentiate the predominantly B-cell infiltrate of PTLD from the T-cell rich infiltrate of rejection.

- The latent EBV proteins LMP-1 and EBNA may be demonstrated by immunohistochemistry in about 50% lesions.

- In situ hybridisation for EBV-encoded RNA (EBER) is positive in over 90% of PTLD.

- The differentiation from rejection is important as the treatment of chocie for PTLD is a reduction rather than an increase in immunosuppression.


3. Cytomegalovirus :   Visit: Cytomegalovirus infection

Courtesy: Cytomegalovirus Induced Interstitial Nephritis and Ureteral Stenosis in Renal Transplant Recipient. Sung Ha Bae, Byung Ha Chung, Yun Kyung Park, Kwanhoon Jo, Chul Woo Yang, Yong-Soo Kim, Bum Soon Choi.Korean J Intern Med. 2012 December; 27(4): 470473. Published online 2012 November 27. doi: 10.3904/kjim.2012.27.4.470

- The transplant kidney is a common site for subclinical cytomegalovirus infection and may also be involved in cytomegalovirus disease.

- In acute infection, cytomegalovirus inclusions and nucleic acid may be seen in tubular epithelium, the epithelium of glomerular and peritubular capillaries and infiltrating leukocytes.

- Infection may be associated with graft dysfunction in the absence of inflammation, but it may produce a glomerulitis or a tubulointerstitial nephritis that resembles acute rejection. In these cases, the presence of cytomegalovirus cytopathic changes is an important differentiating feature.

 "The presentation of CMV may be variable, ranging from asymptomatic infection (as defined by the presence of active viral replication) to end organ or disseminated involvement. Commonly patients present with symptoms of fever and malaise sometimes associated with leukopenia, thrombocytopenia, gastroenteritis, pneumonitis, hepatitis, or more rarely retinal or central nervous system involvement. The type of immunosuppression can affect the presentation and severity of illness." Viral Infection in Renal Transplant Recipients

4. Adenovirus :   Visit:  Adenovirus


Courtesy: Allograft adenovirus nephritis. Kirsty Rady, Giles Walters, Michael Brown, Girish Talaulikar. Clin Kidney J. 2014 Jun; 7(3): 289292.Published online 2014 Mar 23. doi:  10.1093/ckj/sfu020

- Patients presented within 8 months of transplant with gross haematuria, dysuria, fever and acute renal failure. Other less common presentations have been described, including obstructive uropathy and adenovirus nephritis associated with an inflammatory renal mass

- The diagnosis of adenoviral infection has been made by obtaining positive viral culture from blood, urine or tissue, the sensitivity of which has increased with the use of PCR assays.

- A renal allograft biopsy is also essential to differentiate adenoviral nephritis from that of acute rejection or other pathology.

- Typical pathological findings in adenovirus nephropathy include tubular cell necrosis associated with severe interstitial inflammation and viral cytopathic effects including peripheral condensed chromatin, basophilic nuclear inclusions and nuclear enlargement.

- Immunoperoxidase staining is subsequently employed to confirm the presence of adenovirus within the tissue. These viral particles within the tubular epithelial cells are visible under electron microscopy.


Further reading:

Visit related post: Herpes Simplex Virus Infection ; West Nile Virus disease ; Variola ; Varicella ; Herpes Zoster Virus (Shingles).

Viral Infection in Renal Transplant Recipients





Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)

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