Dissertation
Risk of infections with induction therapy among pediatric kidney transplant patients: a comparative safety study
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2025
DOI: 10.17077/etd.006753
Abstract
Background: Induction therapy is an intensive, short-term therapy that is administered at the time of transplantation to prevent rejection and the loss of the transplanted organ. Post-transplant infections are the main cause of hospitalization and death in pediatric kidney transplant patients. Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), and urinary tract infections are among the most common infections occurring within the first year after discharge in this population. However, infection risks associated with different induction types remain poorly characterized in pediatric kidney transplant literature. This study aimed to describe infection patterns, examine associations between induction regimens and infection risk, and assess time to first infection within the first year following pediatric kidney transplantation.
Methods: We conducted a retrospective observational, active-comparator, new-user cohort study design. The United States Renal Disease System (USRDS) dataset was used to identify patients aged <18 years at first kidney transplantation between 2007 and 2019. Patients were classified into four exposure groups based on induction type: basiliximab, antithymocyte globulin (ATG), alemtuzumab, and no induction. Infections were identified using Medicare claims with appropriate ICD-9/10 diagnostic codes. Descriptive statistics utilized ANOVA and Chi-square tests. Inverse probability of treatment weighting balanced measured baseline characteristics across groups. Each infection type was analyzed using multivariable generalized linear models and random-effects Cox regression models. Associations between induction type and infection risk were assessed using odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals.
Results: We identified 1,501 pediatric patients who met the inclusion criteria. Of these, 43% were female. Around 43.3% of patients received ATG and 33.6% received basiliximab. The most frequent infection was UTI (22%), followed by CMV (7.1%) and EBV (5.1%) infections. Compared to basiliximab, alemtuzumab was associated with significantly lower risk of EBV infection (adjusted OR=0.38 [95% CI: 0.15-0.92], adjusted HR=0.32 [95% CI: 0.11-0.97]). Patients receiving no induction therapy had higher odds of UTI compared to those receiving basiliximab (adjusted OR=1.54 [95% CI: 1.06-2.25]). Antiviral and antibacterial prophylaxis therapies independently reduced the risk of viral and bacterial infections, respectively. Recipient age, recipient sex, steroid use, and viral serostatus were among the clinical factors that influenced the risk of infections.
Conclusion: In this study, alemtuzumab induction was associated with a reduced risk of EBV infection compared to basiliximab induction in pediatric kidney transplant patients. This finding may inform induction therapy selection for patients at high risk of EBV infection. Additionally, our results support the use of antiviral prophylaxis in preventing both CMV and EBV infections.
Details
- Title: Subtitle
- Risk of infections with induction therapy among pediatric kidney transplant patients: a comparative safety study
- Creators
- Wesam Walid Ismail
- Contributors
- Amber Goedken (Advisor)Linnea Polgreen (Committee Member)Lyndsay Harshman (Committee Member)Cole Chapman (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Pharmacy (Health Services Research)
- Date degree season
- Summer 2025
- DOI
- 10.17077/etd.006753
- Publisher
- University of Iowa
- Number of pages
- xviii, 153 pages
- Copyright
- Copyright 2025 Wesam Walid Ismail
- Language
- English
- Date submitted
- 07/25/2025
- Description illustrations
- Illustrations, graphs, charts, tables
- Description bibliographic
- Includes bibliographical references (pages 120-134).
- Public Abstract (ETD)
Induction therapy is a group of drugs that help prevent the body from rejecting a new kidney after a transplant. However, these drugs work by weakening the immune system, making the patient more prone to infections. Currently, we do not have enough information about how the use of these drugs affects the risk of infections in children with kidney transplants. In this study, we investigated the risk of developing viral and bacterial infections in children who did or did not use these drugs.
We analyzed medical records of around 1500 children who had kidney transplants at different transplant centers across the United States between 2007 and 2019. Children who received a drug called alemtuzumab had a lower risk of a viral infection called EBV infection than patients who received a drug called basiliximab. We found that a group of medications, called prophylaxis therapy, could be used to prevent these infections effectively.
This research helps doctors choose the best medications for each child. For children at high risk for EBV infections, alemtuzumab might be a better choice.
- Academic Unit
- Pharmacy
- Record Identifier
- 9984948739102771
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