Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN Registry
Introduction: Data on age-related differences in rejection rates, infectious episodes, and tacrolimus exposure in pediatric kidney transplant recipients (pKTRs) on a tacrolimus-based immunosuppressive regimen are scarce. Methods: We performed a large-scale analysis of 802 pKTRs from the Cooperative...
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Elsevier
2024-11-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924019107 |
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| author | Maral Baghai Arassi Manuel Feißt Kai Krupka Atif Awan Elisa Benetti Ali Düzova Isabella Guzzo Jon Jin Kim Birgitta Kranz Mieczysław Litwin Jun Oh Anja Büscher Lars Pape Licia Peruzzi Mohan Shenoy Sara Testa Lutz T. Weber Jakub Zieg Britta Höcker Alexander Fichtner Burkhard Tönshoff |
| author_facet | Maral Baghai Arassi Manuel Feißt Kai Krupka Atif Awan Elisa Benetti Ali Düzova Isabella Guzzo Jon Jin Kim Birgitta Kranz Mieczysław Litwin Jun Oh Anja Büscher Lars Pape Licia Peruzzi Mohan Shenoy Sara Testa Lutz T. Weber Jakub Zieg Britta Höcker Alexander Fichtner Burkhard Tönshoff |
| author_sort | Maral Baghai Arassi |
| collection | DOAJ |
| description | Introduction: Data on age-related differences in rejection rates, infectious episodes, and tacrolimus exposure in pediatric kidney transplant recipients (pKTRs) on a tacrolimus-based immunosuppressive regimen are scarce. Methods: We performed a large-scale analysis of 802 pKTRs from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry from 40 centers in 14 countries. The inclusion criteria were a tacrolimus-based immunosuppressive regimen and at least 2 years of follow-up. The patient population was divided into 3 age groups (infants and young children aged <6 years, school-aged children 6–12 years, and adolescents aged >12 years) to assess age-related differences in outcome. Results: Median follow-up was 48 months (interquartile range [IQR], 36–72). Within the first 2 years posttransplant, infants, and young children had a significantly higher incidence of infections (80.6% vs. 55.0% in adolescents, P < 0.001) and a significantly higher number of cumulative hospital days (median 13 days vs. 7 days in adolescents, P < 0.001). Adolescents had a significantly higher rate of biopsy-proven acute rejection episodes in the first-year posttransplant (21.7%) than infants and young children (12.6%, P = 0.007). Infants and young children had significantly lower tacrolimus trough levels, lower tacrolimus concentration-to-dose (C/D) ratios as an approximation for higher tacrolimus clearance, and higher tacrolimus interpatient variability (TacIPV) (all P < 0.01) than adolescents. Conclusion: This is the largest study to date in European pKTRs on a tacrolimus-based immunosuppressive regimen, and it shows important age-related differences in rejection rates, infection episodes, as well as tacrolimus exposure and clearance. This data suggests that immunosuppressive therapy in pKTRs should be tailored and personalized according to the age-specific risk profiles of this heterogeneous patient population. The data may serve as a benchmark for future studies with novel immunosuppressive drugs. |
| format | Article |
| id | doaj-art-ca6a1b48d17040e08caf0c75fdd127d9 |
| institution | DOAJ |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-ca6a1b48d17040e08caf0c75fdd127d92025-08-20T03:21:18ZengElsevierKidney International Reports2468-02492024-11-019113265327710.1016/j.ekir.2024.08.025Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN RegistryMaral Baghai Arassi0Manuel Feißt1Kai Krupka2Atif Awan3Elisa Benetti4Ali Düzova5Isabella Guzzo6Jon Jin Kim7Birgitta Kranz8Mieczysław Litwin9Jun Oh10Anja Büscher11Lars Pape12Licia Peruzzi13Mohan Shenoy14Sara Testa15Lutz T. Weber16Jakub Zieg17Britta Höcker18Alexander Fichtner19Burkhard Tönshoff20Department of Pediatrics I, Medical Faculty, Heidelberg University, University Children’s Hospital Heidelberg, Heidelberg, Germany; Structural and Computational Biology Unit, European Molecular Biology Laboratory Heidelberg, Heidelberg, Germany; Correspondence: Maral Baghai Arassi, Department of Pediatrics I, University Children’s Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.Institute of Medical Biometry, Heidelberg University, Heidelberg, GermanyDepartment of Pediatrics I, Medical Faculty, Heidelberg University, University Children’s Hospital Heidelberg, Heidelberg, GermanyNational Pediatric Haemodialysis Centre and Renal Transplant Unit, Temple Street Children’s University Hospital, Dublin, IrelandPediatric Nephrology Unit, Department of Women’s and Children’s Health, Padua University Hospital, ItalyDivision of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, TürkiyeDivision of Nephrology, Dialysis and Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Pediatric Nephrology, Nottingham University Hospitals, Nottingham, UKDepartment of General Pediatrics, University Children’s Hospital Münster, Münster, GermanyDepartment of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Warsaw, PolandDivision of Pediatric Nephrology, University Hamburg-Eppendorf, Hamburg, GermanyDepartment of Pediatrics II, University Hospital of Essen, Essen, GermanyDepartment of Pediatrics II, University Hospital of Essen, Essen, GermanyPediatric Nephrology Unit, Regina Margherita Department, Azienda Ospedaliero-Universitaria Città Della Salute e della Scienza, Torino, ItalyDepartment of Pediatric Nephrology, Royal Manchester Children's Hospital, Manchester, UKPediatric Nephrology Unit, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, ItalyPediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Faculty of Medicine, University of Cologne, Köln, GermanyDepartment of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech RepublicDepartment of Pediatrics I, Medical Faculty, Heidelberg University, University Children’s Hospital Heidelberg, Heidelberg, GermanyDepartment of Pediatrics I, Medical Faculty, Heidelberg University, University Children’s Hospital Heidelberg, Heidelberg, GermanyDepartment of Pediatrics I, Medical Faculty, Heidelberg University, University Children’s Hospital Heidelberg, Heidelberg, GermanyIntroduction: Data on age-related differences in rejection rates, infectious episodes, and tacrolimus exposure in pediatric kidney transplant recipients (pKTRs) on a tacrolimus-based immunosuppressive regimen are scarce. Methods: We performed a large-scale analysis of 802 pKTRs from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry from 40 centers in 14 countries. The inclusion criteria were a tacrolimus-based immunosuppressive regimen and at least 2 years of follow-up. The patient population was divided into 3 age groups (infants and young children aged <6 years, school-aged children 6–12 years, and adolescents aged >12 years) to assess age-related differences in outcome. Results: Median follow-up was 48 months (interquartile range [IQR], 36–72). Within the first 2 years posttransplant, infants, and young children had a significantly higher incidence of infections (80.6% vs. 55.0% in adolescents, P < 0.001) and a significantly higher number of cumulative hospital days (median 13 days vs. 7 days in adolescents, P < 0.001). Adolescents had a significantly higher rate of biopsy-proven acute rejection episodes in the first-year posttransplant (21.7%) than infants and young children (12.6%, P = 0.007). Infants and young children had significantly lower tacrolimus trough levels, lower tacrolimus concentration-to-dose (C/D) ratios as an approximation for higher tacrolimus clearance, and higher tacrolimus interpatient variability (TacIPV) (all P < 0.01) than adolescents. Conclusion: This is the largest study to date in European pKTRs on a tacrolimus-based immunosuppressive regimen, and it shows important age-related differences in rejection rates, infection episodes, as well as tacrolimus exposure and clearance. This data suggests that immunosuppressive therapy in pKTRs should be tailored and personalized according to the age-specific risk profiles of this heterogeneous patient population. The data may serve as a benchmark for future studies with novel immunosuppressive drugs.http://www.sciencedirect.com/science/article/pii/S2468024924019107allograft rejectionhospitalizationinfectionpediatric kidney transplantationtacrolimus |
| spellingShingle | Maral Baghai Arassi Manuel Feißt Kai Krupka Atif Awan Elisa Benetti Ali Düzova Isabella Guzzo Jon Jin Kim Birgitta Kranz Mieczysław Litwin Jun Oh Anja Büscher Lars Pape Licia Peruzzi Mohan Shenoy Sara Testa Lutz T. Weber Jakub Zieg Britta Höcker Alexander Fichtner Burkhard Tönshoff Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN Registry Kidney International Reports allograft rejection hospitalization infection pediatric kidney transplantation tacrolimus |
| title | Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN Registry |
| title_full | Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN Registry |
| title_fullStr | Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN Registry |
| title_full_unstemmed | Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN Registry |
| title_short | Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN Registry |
| title_sort | age related differences in rejection rates infections and tacrolimus exposure in pediatric kidney transplant recipients in the certain registry |
| topic | allograft rejection hospitalization infection pediatric kidney transplantation tacrolimus |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924019107 |
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