Treatment with plasmapheresis, immunoglobulins and rituximab for chronic-active antibody-mediated rejection in kidney transplantation: Clinical, immunological and pathological results

AIM: To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection (cAMR) settings. METHODS: We compared 21 kidney transplant recipients (KTRs) with a diagnosis of cAMR in a retrospective case-control analysis: nine KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab (PE-IVIG-RTX group) vs 12 patients (control group) not treated with antibody-targeted therapies. We examined kidney survival and functional outcomes 24 mo after diagnosis. Histological features and donor-specific antibody (DSA) characteristics (MFI and C1q-fixing ability) were also investigated. RESULTS: No difference in graft survival between the two groups was noted: three out of nine patients in the PE-IVIG-RTX group (33.3%) and 4/12 in the control group (33.3%) experienced loss of allograft function at a median time after diagnosis of 14 mo (min 12-max 18) and 15 mo (min 7-max 22), respectively. Kidney functional tests and proteinuria 24 mo after cAMR diagnosis were also similar in both groups. Only microvascular inflammation (glomerulitis + peritubular capillaritis score) was significantly reduced after PE-IVIG-RTX in seven out of eight patients (87.5%) in the PE-IVIG-RTX group (median score 3 in pre-treatment biopsy vs 1.5 in post-treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA characteristics. No functional or histological parameter at diagnosis was predictive of clinical outcome. CONCLUSION: Our data showed no difference in the two year post-treatment outcome of kidney grafts treated with PE-IVIG-RTX for cAMR diagnosis, however there were notable improvements in microvascular inflammation in post-therapy protocol biopsies. Further studies, especially involving innovative therapeutic approaches, are required to improve the management and long-term results of this severe condition.