Abstract
Background and Aims
Antibody Mediated Rejection (ABMR) is a severe complication that frequently occurs after kidney transplantation. The present RCT designed to evaluate the role of adding Bortezomib to standard regimen with plasma exchange, intravenous immunoglobulin and Rituximab in treatment of AMR after kidney transplantation.
Method
26 kidney transplant recipients (KTRs) with a biopsy proven diagnosis of AMR and positive DSA in a randomized clinical trial were compared: Thirteen KTRs treated with plasmapheresis, intravenous immunoglobulin and rituximab (PE-IVIG- RTX ) plus bortezomib versus 13 patients treated with standard of care regimen without bortezomib. We evaluated graft survival and DSA titer with MFI during a year after biopsy proven diagnosis.
Results
Statistical difference in graft survival between the two groups was noted: three out of 13 patients in the PE-IVIG-RTX group (23%) and 1/13 in the bortezomib group (7.5%) experienced loss of allograft function at a median time after diagnosis of 6 month and 12 month, respectively. DSA MFI titers 12 month after AMR diagnosis showed significant reducing slope in Bortezomib group. Regarding pathological changes micro vascular inflammation (glomerulitis + peritubular capillaritis score) reduced after PE-IVIG- RTX plus bortezomib in 7 out of 13 patients whom underwent protocol biopsies after treatment (53%) (Median score 3 in pre- treatment biopsy vs. 1 in post-treatment biopsy; P = 0.036).
Conclusion
Although DSA titer may not differ at 6 months after treatment of AMR between those who received standard regimen and those treated with adding Bortezomib, but at the end of one year patients treated with standard regimen plus Bortezomib reached lower MFI DSA titer. Adding Bortezomib to PE-IVIG- RTX for the treatment of AMR after kidney transplantation may enable clinicians to fight the DSA better and change the future of next generation of highly sensitized kidney transplant candidates.
Protocol biopsies after kidney transplantation
