Tönshoff Burkhard, Patry Christian, Fichtner Alexander, Höcker Britta, Böhmig Georg A
Department of Pediatrics I, Medical Faculty, University Children's Hospital Heidelberg, Heidelberg University, Heidelberg, Germany.
Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Pediatr Transplant. 2025 Feb;29(1):e70008. doi: 10.1111/petr.70008.
The 1- and 5-year patient and graft survival rates of pediatric kidney transplant recipients have improved considerably in recent years. Regardless of early success, kidney transplantation is challenged by suboptimal long-term allograft and patient survival. Many kidney transplants are lost due to immune (rejection) and nonimmune allograft injuries, and patient survival is limited from cardiovascular disease, infection, and malignancy. Many of these co-morbidities are due to side effects of the currently available immunosuppressive drugs, especially calcineurin inhibitors and glucocorticoids, which are associated with long-term toxicity. Hence, there is an urgent need to develop new, more specific and less toxic immunosuppressive drugs. Unfortunately, there have also been no new drug approvals for adult kidney transplant recipients since belatacept in 2012, leaving the immunosuppressive drug armamentarium unchanged for more than 20 years. As a consequence of the lack of innovation in adult kidney transplant recipients, the pipeline of novel immunosuppressive agents for pediatric solid organ transplant recipients is also limited. The most promising agent in the near future, at least for adolescent patients, appears to be belatacept, despite its many limitations. In this review article, we report on three areas that appear to be the most relevant topics at this time: (i) extended-release tacrolimus, (ii) costimulation blockade with belatacept, and (iii) treatment of antibody-mediated rejection. Improved synergies between the pharmaceutical industry and the transplant community are needed to achieve the ultimate goal of improving long-term outcomes in pediatric kidney transplantation.
近年来，小儿肾移植受者的1年和5年患者及移植物存活率有了显著提高。尽管早期取得了成功，但肾移植仍面临长期移植物和患者存活率不理想的挑战。许多肾移植因免疫（排斥）和非免疫性移植物损伤而失败，患者的存活受到心血管疾病、感染和恶性肿瘤的限制。这些合并症中的许多是由于目前可用的免疫抑制药物的副作用，特别是钙调神经磷酸酶抑制剂和糖皮质激素，它们与长期毒性有关。因此，迫切需要开发新的、更具特异性且毒性更小的免疫抑制药物。不幸的是，自2012年贝拉西普以来，成人肾移植受者也没有新的药物获批，免疫抑制药物库在20多年里没有变化。由于成人肾移植受者缺乏创新，小儿实体器官移植受者新型免疫抑制药物的研发渠道也很有限。至少对于青少年患者来说，近期最有前景的药物似乎是贝拉西普，尽管它有许多局限性。在这篇综述文章中，我们报告了目前似乎最相关的三个领域：（i）缓释他克莫司，（ii）贝拉西普共刺激阻断，以及（iii）抗体介导的排斥反应的治疗。为了实现改善小儿肾移植长期预后的最终目标，制药行业和移植界需要更好地协同合作。
