title: The lack of Lazarus effect with proteasome inhibition.
abstract: There have been marked improvements in the short- and long-term outcomes for children after renal transplantation over the past two decades with superior quality and quantity of life. It is encouraging to see increased patient and renal allograft survival rates with initially lower acute renal allograft rejection rates due to improved matching and immunosuppressive regimens. Unfortunately, longer-term renal allograft survival remains unchanged with chronic allograft injury from both immune and non-immune causes, resulting in chronic allograft dysfunction, morbidity from chronic kidney disease, and eventual renal allograft loss. Acute and chronic antibody-mediated rejection remains a clinical dilemma with a growing evidence base of its treatment, including proteasome inhibition using intravenous bortezomib. The future goal is to reduce chronic allograft dysfunction and make renal transplants last longer for pediatric renal transplant recipients who may require retransplantation during their childhood and adult lives, which can become successively more difficult due to sensitization.
authors.affiliation: Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, England, UK. stephen.marks@gosh.nhs.uk.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Marks
mesh_terms: D000069286:Bortezomib / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D061988:Proteasome Inhibitors / Q000627:therapeutic use*
chemical_list: D061988:Proteasome Inhibitors; D000069286:Bortezomib
keywords: Antibody-mediated rejection; Bortezomib; Donor-specific antibodies; Proteasome inhibition; Renal allograft survival; Renal transplantation