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Expanding Cytotoxic T Lymphocytes from Umbilical Cord Blood that Target Cytomegalovirus, Epstein-Barr Virus, and Adenovirus
Published on: May 7, 2012
Targeted preemptive therapy according to perceived risk of CMV infection after kidney transplantation
Cahue Henrique Pinto1, Helio Tedesco-Silva1, Claudia Rosso Felipe1
1Universidade Federal de São Paulo (Unifesp), Hospital do Rim, Disciplina de nefrologia, São Paulo, SP, Brazil.
Background:
The identification of the best strategy to manage cytomegalovirus infection is hampered by uncertainties regarding the risk/benefit ratios of universal prophylaxis versus preemptive therapy, the impact of indirect cytomegalovirus effects and the associated costs. This study investigated the efficacy and safety of targeted preemptive therapy according to perceived risk of cytomegalovirus infection after kidney transplantation.
Methods:
144 adult kidney transplant recipients were enrolled in this 12-month study. None received cytomegalovirus pharmacological prophylaxis. Only high risk patients (positive donor/negative recipient (D+/R-), use of induction therapy with antithymocyte globulin, treatment of rejection) received preemptive therapy based on the result of pp65 antigenemia test. Low-risk patients with symptoms related to cytomegalovirus were screened for pp65 antigenemia and treatment initiated if confirmed cytomegalovirus disease. Blinded cytomegalovirus DNAemia was collected weekly during the first three months.
Results:
The incidence of cytomegalovirus infection was 34% and cytomegalovirus disease was 17%. The incidence was 25% in D+/R-, 69% in those receiving induction with rabbit antithymocite globulin (r-ATG), 46% in those treated for acute rejection, and 28% in low risk patients. By week 3 DNAemia was observed in 30% of patients who were not treated for cytomegalovirus infection/disease, and values ≥2.169UI/mL showed 61% sensitivity and 85% specificity to detect cytomegalovirus disease (AUC=0.849±0.042, p<0.001). Using multivariate analysis, only anti-thymocyte globulin induction was associated with cytomegalovirus infection/disease whereas only expanded donor criteria and renal function at 30 days were associated with renal function 12 months after transplantation.
Conclusion:
Targeted preemptive therapy in patients with perceived higher risk for cytomegalovirus infection/disease was effective in preventing severe clinical presentation, including tissue invasive and late cytomegalovirus infection. This strategy is associated with direct and indirect cost-savings.
Insights
Targeted preemptive therapy for cytomegalovirus (CMV) infection after kidney transplant effectively prevented severe disease in high-risk patients. This approach offers cost savings and avoids universal prophylaxis risks.
Area of Science:
- Nephrology
- Infectious Diseases
- Transplantation Immunology
Background:
- Managing cytomegalovirus (CMV) infection post-kidney transplant involves balancing prophylaxis and preemptive therapy risks and costs.
- Uncertainties exist regarding CMV's indirect effects and optimal management strategies.
Purpose of the Study:
- To evaluate the efficacy and safety of a targeted preemptive therapy strategy for CMV infection in kidney transplant recipients.
- To assess this strategy based on perceived risk of CMV infection.
Main Methods:
- 144 adult kidney transplant recipients were studied over 12 months without universal CMV prophylaxis.
- High-risk patients (donor positive/recipient negative, antithymocyte globulin induction, or rejection treatment) received preemptive therapy guided by pp65 antigenemia.
- Low-risk patients with symptoms were screened, and treatment initiated if CMV disease was confirmed.
Main Results:
- The incidence of CMV infection was 34%, and CMV disease was 17%.
- High-risk groups showed varying incidence rates (e.g., 69% with rabbit antithymocyte globulin induction).
- Multivariate analysis linked only antithymocyte globulin induction to CMV infection/disease.
Conclusions:
- Targeted preemptive therapy effectively prevented severe clinical presentations of CMV infection and disease in high-risk kidney transplant patients.
- This strategy demonstrated cost-effectiveness through direct and indirect savings.
- The approach successfully mitigated tissue-invasive and late-onset CMV infections.
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