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Published on: May 27, 2011
Preemptive Conversion to mTOR Inhibition to Prevent Primary Cytomegalovirus Infection in Kidney Transplantation with
Jan Paulwitz1, Laura Vonbrunn1, Katharina Heller1
1Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Background:
Kidney transplantation (KTx) is the treatment of choice for patients with end-stage renal disease. Cytomegalovirus (CMV) infection remains a serious complication of KTx. The most vulnerable patients are naïve recipients (R-) transplanted from a CMV-seropositive donor (D+). Mammalian target of rapamycin inhibitors (mTOR-I) have been shown to have advantages over mycophenolate in terms of CMV infections. In this study, we addressed the effect of preemptive conversion to mTOR-I before ending prophylaxis with valganciclovir in high-risk patients with a D+/R- CMV serostatus.
Methods:
The study involved inclusion and analysis of all patients with D+/R- CMV serostatus before and after the protocol change with a conversion to mTOR-I at 6 months after KTx. The main study endpoints were primary CMV infection, maximal viral load, and hospitalization for CMV infection. Because prevention of primary CMV infections was the primary endpoint, we excluded breakthrough infections under prophylaxis.
Results:
The primary analysis included 44 patients in the control group and 39 patients in the mTOR group. The 2 groups did not have any significant differences in clinical characteristics, immunosuppressive treatment, transplant function, and rates of rejection. Between 6 and 12 months (when mTOR-I were established), the mTOR group showed a numerically lower incidence of CMV infections, as well as numerically fewer hospitalizations. No serious complications were observed with mTOR-I.
Conclusion:
Preemptive conversion from mycophenolate to mTOR-I may be helpful to prevent or attenuate primary infection in CMV high-risk kidney transplant recipients. Differences were not statistically significant. A larger study, ideally a prospective randomized trial, is needed to validate these findings.
Insights
Converting to mTOR inhibitors may help prevent Cytomegalovirus (CMV) infection in high-risk kidney transplant recipients. This strategy showed a numerical decrease in CMV infections and hospitalizations, though not statistically significant.
Area of Science:
- Nephrology
- Transplantation Immunology
- Infectious Diseases
Background:
- Kidney transplantation (KTx) is the preferred treatment for end-stage renal disease.
- Cytomegalovirus (CMV) infection is a significant complication following KTx, particularly in CMV-seropositive donor to CMV-naïve recipient (D+/R-) cases.
- Mammalian target of rapamycin inhibitors (mTOR-I) may offer advantages over mycophenolate in managing CMV infections post-KTx.
Purpose of the Study:
- To evaluate the effect of preemptive conversion to mTOR-I before stopping valganciclovir prophylaxis.
- To assess the impact on high-risk D+/R- kidney transplant recipients.
- To analyze primary CMV infection rates, viral load, and hospitalizations.
Main Methods:
- Retrospective analysis of D+/R- patients before and after a protocol change.
- Conversion to mTOR-I at 6 months post-KTx.
- Exclusion of breakthrough CMV infections under prophylaxis for primary endpoint analysis.
Main Results:
- The mTOR inhibitor group (39 patients) showed numerically lower CMV infection incidence and hospitalizations compared to the control group (44 patients) between 6 and 12 months post-KTx.
- No significant differences in clinical characteristics, immunosuppression, transplant function, or rejection rates were observed between groups.
- No serious complications were associated with mTOR-I use.
Conclusions:
- Preemptive conversion to mTOR-I may help prevent or reduce primary CMV infection in high-risk kidney transplant recipients.
- Observed differences were not statistically significant, indicating a need for further investigation.
- A larger prospective randomized trial is recommended to validate these preliminary findings.
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