Primary Cytomegalovirus Infection in Seronegative Kidney Transplant Patients Is Associated with Protracted Cold Ischemic Time of Seropositive Donor Organs

Abstract

Human Cytomegalovirus (CMV) can lead to primary infection or reactivation in CMV-seronegative or -seropositive kidney transplant recipients, respectively. Complications comprise severe end-organ diseases and acute or chronic transplant rejection. Risk for CMV manifestation is stratified according to the CMV-IgG-serostatus, with donor+/recipient- (D+/R-) patients carrying the highest risk for CMV-replication. However, risk factors predisposing for primary infection in CMV-seronegative recipients are still not fully elucidated. Therefore, we monitored D+/R- high-risk patients undergoing kidney transplantation in combination with antiviral prophylaxis for the incidence of CMV-viremia for a median follow-up time of 784 days (156–1155 days). In this period, we analyzed the functional CMV-specific T cell response by intracellular cytokine staining and CMV-serology by ELISA. Only four of eight D+/R- patients developed clinically relevant CMV-viremia followed by seroconversion. Viremia triggered expansion of functional CMV-specific T cells correlating with protection against secondary CMV-reactivations. In contrast, all other patients remained permanently aviremic and showed no immunological correlate of infection after discontinuation of antiviral prophylaxis for up to three years. Comparing cold ischemic times (CIT) of viremic (median = 1020 min; 720–1080 min) and aviremic patients (median = 335 min; 120–660 min) revealed significantly (p = 0.0286) protracted CIT in patients with primary CMV-infection. Taken together, primary CMV-infection affects only a subgroup of D+/R- patients correlating with length of CIT. Therefore, patients with extended CIT should be thoroughly monitored for CMV-replication well beyond discontinuation of antiviral prophylaxis. In contrast, patients with short CIT remained permanently uninfected and might benefit from shorter prophylactic treatment.

Factors Contributing to Kidney Allograft Loss and Associated Consequences among Post Kidney Transplantation Patients

“…Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) disease and asymptomatic infection have been associated with poor outcomes in kidney transplantation [77][78][79]. Recipients who acquire primary infection through transplantation from a seropositive donor may be at particular risk of complications [77,78,80].…”

“…Recipients who acquire primary infection through transplantation from a seropositive donor may be at particular risk of complications [77,78,80]. According to these authors these herpes viruses, both CMV and EBV achieve a latent state within a host after primary infection and may reactivate in the setting of immunosuppression.…”

“…According to these authors these herpes viruses, both CMV and EBV achieve a latent state within a host after primary infection and may reactivate in the setting of immunosuppression. Chronic allograft damage and dysfunction has also been linked to both CMV and EBV and may occur in the absence of symptomatic infection [77,78,80]. Recurrent glomerulonephritis is a known cause of allograft loss [81].…”

Oral Ulcers Induced by Cytomegalovirus Infection: Report on Two Cases

“…6,9,[10][11][12][13][14][15][16][17][18] The most common manifestation is retinitis, which is responsible for many cases of symptoms of CMV infection. In the mouth, this virus can cause oral hairy leukoplakia, especially in patients with compromised immune systems.…”

“…6,9 In addition, other clinical manifestations are associated with CMV infection, including pancytopenia, infectious mononucleosis syndrome, infection in the CNS, and retinitis. 6,9,[10][11][12][13][14][15][16][17][18] However, oral manifestations of CMV infection are considered rare. 19 Although oral lesions resulting from CMV infection have been documented in several immunosuppressive conditions, oral involvement CMV has increased since the beginning of the AIDS epidemic.…”