Burkhard Tönshoff, MD, PhD, is professor of pediatrics and pediatric nephrology at the University Children’s Hospital Heidelberg, Germany; Vice Chairman of the Department of Pediatrics I (General Pediatrics, Neuropediatrics, Metabolism, Gastroenterology, and Nephrology); Medical Director of the Pediatric Kidney Transplantation Program. His current research focuses on various issues in acute and chronic kidney disease and renal transplantation, such as studies on the pharmacokinetics, efficacy and safety of novel immunosuppressive drugs in pediatric renal transplant recipients, optimization of immunosuppressive therapy by therapeutic drug monitoring and immune monitoring, prevention of infectious and other complications after renal transplantation, biomarker-guided minimization of immunosuppressive therapy and the impact of donor-specific HLA and non-HLA antibodies on graft histology and function. In the year 2009 he founded the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN; www.certain-registry.eu) as a multicenter research network and platform built on a novel, web-based registry. Other research activities focus on the pathophysiology and therapy of the nephrotic syndrome, biomarker research for acute kidney injury, the role of endothelial progenitor cells and mesenchymal stem cells in various pediatric kidney diseases and the role of the gut microbiome in solid organ transplantation.
Awards and nominations: Eurotransplant Kidney Advisory Committee. Scientific Steering Committee der DZIF Transplantationskohorte e.V.. Chair, Working Group “Renal Transplantation” of the European Society for Paediatric Nephrology (ESPN) and of the German Society for Paediatric Nephrology (GPN). Council of the International Pediatric Transplant Association (IPTA); 2015 - 2017 President of IPTA. Since 2018 Editor-in-Chief of the journal “Pediatric Transplantation”, the official journal of IPTA.
Incidence, risk factors, treatment strategies and outcome of antibody-mediated rejection in paediatric kidney transplant recipients – a multicentre analysis of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN)
Alexander Fichtner1, Laura Gauché1, Britta Hoecker1, Caner Suesal12, Susanne Rieger1, Christian Patry1, Sabine Koenig7, Matthias Zirngibl8, Anja Buescher5, Jun Oh6, Atif Awan9, Jon Jin Kim3, Luisa Murer11, Stephen Marks2, Lutz Weber4, Lars Pape5, Luca Dello Strologo10, Burkhard Toenshoff1.
1Pediatric Nephrology, Heidelberg, Germany; 2Pediatric Nephrology, London, United Kingdom; 3Pediatric Nephrology, Nottingham, United Kingdom; 4Pediatric Nephrology, Cologne, Germany; 5Pediatric Nephrology, Essen, Germany; 6Pediatric Nephrology, Hamburg, Germany; 7Pediatric Nephrology, Muenster, Germany; 8Pediatric Nephrology, Tuebingen, Germany; 9Pediatric Nephrology, Dublin, Ireland; 10Pediatric Nephrology, Rome, Italy; 11Pediatric Nephrology, Padua, Italy; 12Immunology, Istanbul, Turkey
CERTAIN study group.
Introduction: Late antibody-mediated rejections (ABMR) are further on one of the leading causes for premature kidney transplant (KTx) loss in adults. However, data on incidence, risk factors, treatment strategies and outcome of ABMR in paediatric patients are scarce. Therefore, the aim of this multicentre approach was to investigate this topic within the framework of the paediatric European Transplantation Research Network CERTAIN.
Methods: Data on donor-specific HLA antibodies (HLA-DSA), biopsy findings, immunosuppressive therapy and graft function were documented in specific query forms in CERTAIN. Inclusion criteria were (i) regular monitoring of HLA-DSA (by SAB-assay) at least once per year posttransplant and/or (ii) at least one HLA-DSA measurement at time of a clinically indicated KTx biopsy.
Results: 19 centres from seven European countries participated in this study. Until September 2021, 331 patients, who fulfilled the inclusion criteria, were documented in the specific dataset. The cumulative incidence of acute ABMR up to 5 years posttransplant was 10.8%, and that of chronic ABMR was 5.9%. Risk factors for the development of ABMR were the number of HLA-mismatches, evidence of de novo HLA-DSA, and T-cell-mediated rejection (TCMR) before ABMR. 81% of patients received a tacrolimus-based maintenance immunosuppressive regimen. ATG or monoclonal antibodies were used in 65% of ABMR episodes; IVIG were applied in 48%. By cox regression models with time-dependent covariates, ABMR (HR 2.9; p<0.001), TCMR (HR 2.1; p=0. 02), and BK polyomavirus-associated nephropathy (HR 4.2; p<0.001) were identified as relevant risk factors for premature graft function deterioration, defined as eGFR decline below <50% of baseline or eGFR <30 mL/min*1.73 m2 BSA.
Conclusion: The results of this multicentre approach underscore the importance of ABMR as major risk factor for premature graft function deterioration in paediatric KTx recipients. There was considerable variability among centres regarding treatment strategies of ABMR subtypes. In all, standardization of treatment of ABMR by an evidence-based guideline and the introduction of novel drugs for more effective therapy are urgently needed to improve outcome.
