CHAPTER 29: Virus Infections in Renal Transplant Recipients

INTRODUCTION

Solid organ transplant recipients (SOTRs) are at high risk of viral infections due to their immunosuppressed state. After cardiovascular causes, infections are the leading cause of death in renal transplant recipients (RTRs). Most viral infections occur as reactivation of latent/dormant viruses from the host or the graft. This reactivation can occur because of immunosuppression, use of therapy for graft rejection, or inflammation and tissue injury.

Viral infections can have both direct and indirect effects:

1. Direct effects – fevers, neutropenia, encephalitis, meningitis, enteritis, pneumonia, and other invasive syndromes

2. Indirect effects – more profound immunosuppression and increased risk of opportunistic infections, graft rejection, graft-versus-host disease (GVHD), and occurrence of neoplasms

The management of some of these viral infections includes reducing immunosuppression to varying degrees. This must be balanced by the individual risk of allograft rejection.

CYTOMEGALOVIRUS/HUMAN HERPESVIRUS-5

Pathophysiology

Cytomegalovirus (CMV) was first reported in 1956 after being isolated as inclusions in infant tissues. After primary infection, it remains latent in myeloid cell lines. It is the most common virus infecting RTRs. In comparison to other SOTRs, RTRs are at lower risk for CMV, partly due to lower burden of latent virus in the renal allograft.

Risk factors for CMV include transplantation from a seropositive donor to a seronegative recipient, use of lymphocyte-depleting therapies (antithymocyte globulin, alemtuzumab), and coinfection with human herpesviruses 6 and 7 (HHV-6/7). The type of immunosuppression can affect the severity and duration of infection.

In the absence of prophylaxis, acute infection occurs between the first and third months after transplant (time of maximal immune suppression). If prophylactic antivirals are used, onset is delayed until after cessation of prophylaxis (usually in the first year after transplant).

CMV may be transmitted to SOTRs via infected donor organs or cellular blood products. There are three major patterns of CMV transmission observed in SOTRs:

1. Primary infection – when a CMV-seronegative recipient receives cells latently infected with the virus from a CMV-seropositive donor.

2. Secondary infection/reactivation – when reactivation of endogenous latent virus occurs after transplant in a CMV-seropositive recipient.

3. Superinfection/reinfection – when a CMV-seropositive recipient receives latently infected cells from a seropositive donor and the donor virus reactivates posttransplant.

Clinical Features

1. Asymptomatic infection – CMV replication without clinical disease.

2. “CMV syndrome” – fever, malaise, anorexia, arthralgias/myalgias, headache, malaise, leukopenia, thrombocytopenia, mild lymphocytosis with atypical lymphocytes, mild hepatitis/transaminitis.

3. “Compartmentalized disease” – tissue invasive disease due to CMV in the absence of viremia. It is commonly seen with gastrointestinal manifestations.

4. “CMV disease” – systemic symptoms of CMV syndrome with end-organ involvement/tissue invasive disease: gastroenteritis, colitis, hepatitis; pneumonitis, interstitial pneumonia; nephritis, cystitis, epididymitis; chorioretinitis, central nervous system (CNS) involvement.

5. Allograft dysfunction – acute/chronic manifestations, accelerated vascular disease (atherosclerosis).

6. Increased risk of allograft rejection.

7. Immunomodulating activity – ...