Antibody‐mediated rejection after kidney transplantation in children; therapy challenges and future potential treatments

Abstract

Antibody-mediated rejection (AMR) remains one of the most critical problems in renal transplantation, with a significant impact on patient and graft survival. In the United States, no treatment has received FDA approval jet. Studies about treatments of AMR remain controversial, limited by the absence of a gold standard and the difficulty in creating large, multi-center studies. These limitations emerge even more in pediatric transplantation because of the limited number of pediatric studies and the occasional use of some therapies with unknown and poorly documented side effects. The lack of recommendations and the unsharp definition of different forms of AMR contribute to the challenging management of the therapy by pediatric nephrologists. In an attempt to help clinicians involved in the care of renal transplanted children affected by an AMR, we rely on the latest recommendations of the Transplantation Society (TTS) for the classification and treatment of AMR to describe treatments available today and potential new treatments with a particular focus on the pediatric population.

Antibody‐mediated rejection in pediatric kidney transplant recipients: A report from the Pediatric Nephrology Research Consortium

“…DISCUSS IONIn this study, we describe the natural history, treatment approaches, and outcomes of antibody-mediated rejection in the largest contemporary multicenter study in pediatric kidney transplant recipients to date. Previous studies in this area have been limited by their singlecenter nature and/or smaller sample size limiting the generalizability of their findings 11. As expected, given the lack of high-quality evidence and consensus recommendations regarding AMR treatment in pediatric or adult kidney transplant recipients, we identified a wide variation in AMR treatment protocols.…”

“…In this study, we describe the natural history, treatment approaches, and outcomes of antibody‐mediated rejection in the largest contemporary multicenter study in pediatric kidney transplant recipients to date. Previous studies in this area have been limited by their single‐center nature and/or smaller sample size limiting the generalizability of their findings 11 …”

Significance of anti-endothelial cell antibodies in paediatric kidney transplant recipients

“…Most centres do not use ATG as a standard treatment and reserve its use for AMR with a significant vascular component or concomitant TCMD. The main concern is the risk of long-term development of malig- [23].…”

Carfilzomib‐based antibody mediated rejection therapy in pediatric kidney transplant recipients

“…3 Therapies for AMR include intravenous immunoglobulin (IVIG), plasmapheresis (TPE), anti-CD20 antibodies, proteosome inhibitors (PI), 4 and other therapies. 5,6 The PI bortezomib has been used with rituximab, TPE, and IVIG for AMR with good results in early AMR but with lesser efficacy in late AMR. 3,[7][8][9] Importantly, bortezomib is associated with adverse effects that may limit dosing in a subset of patients, including peripheral neuropathy, gastrointestinal symptoms, anemia, leukopenia, and thrombocytopenia.…”

“…These benefits are limited by antibody mediated rejection (AMR), a leading cause of allograft failure 3 . Therapies for AMR include intravenous immunoglobulin (IVIG), plasmapheresis (TPE), anti‐CD20 antibodies, proteosome inhibitors (PI), 4 and other therapies 5,6 . The PI bortezomib has been used with rituximab, TPE, and IVIG for AMR with good results in early AMR but with lesser efficacy in late AMR 3,7–9 .…”