Cellular Immunity to Predict the Risk of Cytomegalovirus Infection in Kidney Transplantation: A Prospective, Interventional, Multicenter Clinical Trial
Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies.
METHODS:This prospective, interventional, multicenter clinical trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γ release assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)-specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy.
RESULTS:Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio [OR], 3.44 [95% confidence interval {CI}, 1.30-9.08]) and prophylaxis (33.3% vs 4.1%; OR, 11.75 [95% CI, 2.31-59.71]) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 [95% CI, 7.89-237.96]).
CONCLUSIONS:Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell-depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation.
CLINICAL TRIALS REGISTRATION:NCT02550639.
CET Conclusion
| Reviewer: | Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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| Conclusion: | This somewhat complicated multicenter study investigated the use of pre-transplant testing for CMV-specific cell mediated immunity (using Elispot) to predict risk of post-transplant CMV infection. Patients were stratified into 2 groups according to pre-transplant immunity, and then each group was randomized to pre-emptive or prophylactic CMV prevention strategy post-transplant. The authors found that pre-transplant immunity predicts risk of post-transplant CMV infection, but this prediction is affected by the use of lymphocyte depleting induction agents. Measuring CMV CMI at day 15 post-transplant appears to offer better prediction of risk. It should be noted that the minority of patients received lymphocyte depleting agents so the power to detect differences in this subgroup is very small (the confidence intervals around the odd-ratios given are wide). Also, the randomized intervention was the CMV prevention strategy, rather than the monitoring strategy that is compared in the primary outcome, meaning that this is really an observational rather than randomized study. |
Methodological quality
| Jadad score | 2 |
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| Allocation concealment | YES |
| Data analysis | INTENTION TO TREAT |
Study Details
| Aims: | The aim of this study was to investigate whether assessing pre-transplant Cytomegalovirus (CMV)-specific cell mediated immunity (CMI) could predict the risk of CMV infection in transplant patients |
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| Interventions: | Participants were first categorized as low risk or high risk based on CMV-specific CMI, and then subsequenty randomized to two groups: the 3-month antiviral prophylaxis group or the preemptive therapy group. |
| Participants: | 160 CMV-seropositve renal transplant donors/recipients. |
| Outcomes: | The primary outcome was the incidence of CMV infection. The secondary outcomes included rate of CMV infection in need of antiviral treatment, CMV disease rate and the rate of late-onset CMV infection following prophylaxis withdrawal; the influence of CMV-specific CMI based on the type of induction therapy; the effect of CMI on the pp65 CMV antigen; and the accuracy of prediction-risk of pre-transplant CMV-specific CMI after 15 days of transplantation. |
| Follow Up: | 1 year |
Metadata
| Funding: | Non-industry funding |
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| Publication type: | Multicenter Study, Randomized Controlled Trial, Randomised Controlled Trial |
| Trial registration: | ClinicalTrials.gov - NCT02550639 |
| Organ: | Kidney |
| Language: | English |
| Author email: | obestard@ bellvitgehospital.cat |
| MeSH terms: | Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunity, Cellular; Kidney Transplantation; Prospective Studies; 0 (Antiviral Agents); Cell-Mediated Immunity; Immune Monitoring |