Background Transplantation has become an important treatment option in children with end-stage renal dis-ease. In the last decades progress in immunosuppressive treatment options and surgical techniques have reduced the frequency of acute rejection, graft loss and mortality. However, adverse events occur in patients treated with immunosuppressive therapy. These adverse events are well described for adults but few data are available for children. Our objective was to describe the frequency of adverse events (AEs) under different immunosuppres-sive regimen including either ciclosporin or tacrolimus in children after renal transplantation. Secondary objectives include comparison of AEs with known adverse drug re-actions (ADRs) as described in the Summary of Product Characteristics. Furthermore, risk factors for AEs will be examined.
Methods Children receiving a renal transplant at our institution between 2002 to 2015 were included in the study. Initial immunosuppression was obtained by thy-moglobulin or monoclonal antibody, calcineurin inhib-itors (tacrolimus or ciclosporin), mycophenolate mofetil, and corticoids. AEs reported after transplantation were collected from medical reports and coded using Med-DRA (version 19.1). Descriptive statistical analyses were performed using SAS 9.4. Data were stratified by tacrolim-us or ciclosporin treatment schedule at the time of the AE.
Results A total of 164 children fulfilled the inclusion cri-teria. Finally, complete medical records were available for 125 children (53 girls and 72 boys). The median age was 12 (2 – 19) years old. The indication for renal transplan-tation included congenital, familial and genetic disorders for 61% of the patients and renal and urinary disorders for 39% (including 30% of nephritis). The median time of observation until last follow up was 2.7 (0.6–4.3) years. Initially, 91 patients were treated with tacrolimus and 34 with ciclosporin. During the observation period 6 patients switched from tacrolimus to ciclosporin and 14 switched from ciclosporin to tacrolimus.
A total of 1520 AEs were reported. For patients receiving tacrolimus 1122 AEs (233.6 person-years of exposure) were reported and 372 AEs (71.4 person-years of expo-sure) for those treated with ciclosporin. Twenty-six AEs were reported in patients not receiving any calcineurin inhibitor. The most frequent medical AEs reported for pa-tients treated with tacrolimus and ciclosporin by system organ class were renal and urinary disorders (0.3 vs 0.3 AEs per person-year of exposure), infections (0.3 vs 0.4 AEs per person-year of exposure), vascular disorders (0.2 vs 0.3 AEs per person-year of exposure) and gastrointestinal disor-ders (0.2 vs 0.2 AEs per person-year of exposure). For 46 patients at least one episode of transplant rejection was reported.
Conclusion This study describes AEs up to 4 years after renal transplantation in children treated with immuno-suppressive therapy. Our findings will contribute to the understanding of the benefit-risk balance of immuno-suppressive therapy following renal transplantation in children.
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