Desensitization protocol for highly sensitized renal transplant patients: A single-center experience

Abstract

Highly sensitized patients are destined to remain untransplanted for long. Early transplantation results in cost-saving, reduced morbidity/mortality and improved quality of life. We carried out a prospective study to evaluate the efficacy and safety of desensitization protocol vis-à-vis patient/graft survival in living donor renal transplantation in highly sensitized patients. Between December 2008 and April 2010, 34 renal transplant (RTx) patients underwent desensitization protocol. An anti-human globulin-enhanced lymphocytotoxicity crossmatch assay (AHG-CDC) ≥25% and T-cell median channel shift (MCS) >50, B-cell MCS >100 [flow crossmatch (FXM)] were considered crossmatch (XM) positive. All patients were administered bortezomib (1.3 mg/m 2 , days 1, 4, 8, 11), plasmapheresis, rabbit-anti-thymocyte globulin (r-ATG), mycophenolate mofetil (MMF) and intravenous immunoglobulins (IVIg). LCXM and FXM were repeated post-protocol. In the event of persistent sensitization, additional bortezomib cycle was repeated along with plasmapheresis, IVIg, calcineurin inhibitors (CNI) and rituximab. If the cross match (CMX) was negative or acceptable, patients underwent RTx. Post-transplant immunosuppression consisted of prednisone, CNI and MMF. Biopsy was performed in the event of graft dysfunction and treated accordingly. There were 18 males and 16 females, with a mean age of 37.4 years. Mean dialysis duration was 14.9 ± 17.6 months. Average third party transfusions were 6.2 ± 4.5, 17.6% had autoimmune diseases, 20.6% were multi-para. Pre-protocol AHGXM was 55.3 ± 24.5%, T-cell crossmatch (TCXM) was 122.4 ± 91.4 MCS and B-cell crossmatch (BCXM) was 279 ± 142.9 MCS. Totally, 85.3% responded within 1 month with reduction in AHG-CDC to 19.9 ± 5.2%, TCXM to 24.7 ± 19.4 MCS and BCXM to 74.7 ± 34.8 MCS. Side effects noted in 38.2% were manageable. Over follow-up of 0.92 ± 0.8 years, patient/graft survival was 100%/88.2% and mean serum creatinine was 1.27 ± 0.32 mg/dL. Acute rejections were noted in 24.1%, who responded to steroids + rabbit antithymocyte globulin (rATG). Five (14.7%) patients were transplanted after changing donors. Our desensitization protocol seems to be safe and effective. Bortezomib may offer new possibilities in desensitization protocols.