AMR at time of bortezomib treatment was considered early if it occurred 6 months post-transplant and late AMR was defined as occurring 6 months post-transplant . was more effective for Class I than Class II. Conclusions Bortezomib appears safe and may correlate with stabilization of eGFR in pediatric kidney transplant patients with refractory C4d+ AMR. DSA undergo renal biopsies (MFI 1000 are considered positive) . For DSAs alone without biopsy changes, treatment includes closer monitoring and high dose IVIG (2g/kg given over 2 days) for MFI 2000. For DSA with biopsy changes (either histological evidence and/or C4d+), methylprednisolone pulse (10mg/kg/dose 3 days), high dose IVIG, and rituximab (375mg/m2) are given. For high MFI DSA ( 5000) and creatinine increasing by 50%, plasmapheresis 1x volume exchange with albumin replacement 3 times a week is initiated. Antithymocyte globulin (ATG) is usually given for concurrent acute cellular rejection (ACR) 1B or higher. Our bortezomib protocol is based on the protocol of the START collaborative . Plasmapheresis is done on days 1,4,8,15,17,19, and 22 immediately prior to bortezomib administration. Rituximab 375 mg/m2 (day 1), 4 doses of bortezomib 1.3 mg/m2/dose (days 1,4, 8,15), and IVIG 1g/kg around the last day of treatment (day 22) are given with each round of treatment. Rituximab Biotinyl Cystamine is usually primarily given with the first round of therapy and is not readministered in patients who have received it previously. Each dose of bortezomib is usually preceded by methylprednisolone, acetaminophen, and diphenhydramine premedications. Valganciclovir and sulfamethoxazole/trimethoprim prophylaxis in addition to viral monitoring for BK computer virus, cytomegalovirus, and Epstein-Barr computer virus with PCR was initiated and continued for 1 year post-bortezomib protocol. Patient Selection and Evaluation This is a single center retrospective review of 7 pediatric kidney transplant patients with refractory C4d+ AMR treated with bortezomib at Mattel Childrens Hospital, UCLA Biotinyl Cystamine between November 2011 and January 2014. This retrospective chart review was performed in accordance with the UCLA institutional review board (IRB #11-003592) and formal patient consent is not Biotinyl Cystamine required. Additionally, this report conforms with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The overall prevalence of biopsy confirmed C4d+ AMR in our patient population over the report period Rabbit polyclonal to IGF1R was approximately 12%. Patients were selected for treatment with the bortezomib protocol if their pre-bortezomib renal biopsy exhibited C4d+ AMR and they were refractory to AMR treatment based on meeting 2 of 3 of the following criteria: 1) persistent or worsening biopsy findings, 2) persistent or increasing DSAs that did not decrease by 30% for MFI 10,000 or by 50% for MFI 10,000 or 3) declining graft function for 1 month despite treatment with the above described protocols. Persistent or worsening biopsy findings Biotinyl Cystamine included progression from no rejection to AMR, progression from ACR to AMR, or persistence of AMR on biopsy. The standard UCLA immunosuppressive regimen for pediatric transplant recipients included induction with either ATG for high risk patients (cPRA 30% or delayed graft function) or anti-CD 25 monoclonal antibody for low risk patients cPRA 30%. Maintenance immunosuppression included steroid based immunosuppression, a calcineurin inhibitor, and an anti-metabolite. AMR at time of bortezomib treatment was considered early if it occurred 6 months post-transplant and late AMR was defined as occurring 6 months post-transplant . In addition to the protocol surveillance biopsies mentioned above, patients underwent biopsies for cause based on positive DSAs with or without declining graft function. All biopsies were evaluated based on the 2013 Banff Criteria . Patients underwent biopsies at the following time points: prior to any treatment for AMR, within 3 months prior to bortezomib treatment, and within 1 month after bortezomib protocol completion. The eGFR is usually reported as a measure of renal function and was calculated using the updated Schwartz equation . Non-adherence was defined as physician and/or clinic staff documentation of patient report.