KIDNEY - ACUTE GRAFT INJURY

W.R. Mulley¹, J. Dowling¹, F. Hudson², L.S. Cantwell², R. Holdsworth², J. Kanellis^3
1Department Of Nephrology, Monash Medical Centre, Clayton/AUSTRALIA, ²Victorian Transplantation And Immunogenetics Service, Australian Red Cross Blood Service, Parkville/AUSTRALIA, ³Nephrology, Monash Medical Centre, Clayton/VIC/AUSTRALIA

Body: Introduction: Antibody-mediated rejection (AMR) is associated with poor short-term allograft survival whilst longer-term outcomes are not well described. We have previously reported excellent short-term outcomes for 7 patients treated for refractory AMR with a protocol which includes the use of low-dose rituximab. We now present longer-term follow-up data for 18 patients treated using this protocol. Methods: Our protocol for the treatment of AMR includes 4 weeks of plasma exchange with low-dose IVIg (PE/IVIg) on background maintenance immunosuppression of Tac/MMF/PNL. Patients are designated as refractory if they continue to exhibit ongoing biopsy evidence of AMR after 4 weeks of PE/IVIg. In this group of patients a single, low, fixed-dose of rituximab (500mg) is administered and PE/IVIg is ceased. We prospectively monitored patient and graft survival in patients treated as such since the protocol’s introduction. Peripheral B-cell counts, urinary protein creatinine ratios and renal function were also followed. Results: Since July 2005, we have 18 patients with greater than 12 months follow-up (median follow-up 23 months (range 13-62)) post treatment with rituximab for refractory AMR. Seventeen patients have an identified donor specific antibody (2 after IgM depletion). Patient and graft survival during this period were 100% and 88.9% respectively (12 month graft survival was 94.4%). GFR and proteinuria data are shown below. Two patients have lost their grafts; patient 17 at day 10 (severe vascular rejection) and patient 4 at 19 months (non-compliance). Peripheral blood B-cells were undetectable for ≥6 months post-rituximab in most patients (78.6%). Rituximab did not eliminate the need for further therapy in all patients with 2 patients requiring splenectomy for ongoing AMR. In these patients diminished B-cells were noted in the removed spleens whilst plasma cells were preserved. Patient 1 received a second rituximab dose and 10 patients have received subsequent IVIg therapy. During the follow-up period four patients have developed infective complications, including CMV viraemia and BK nephropathy, all have resolved. One patient has developed a renal cell carcinoma. Conclusions: Our protocol for treating refractory AMR resulted in improved graft survival compared to historic reports with low rates of infective and malignant complications. It does not however provide complete protection from this increasingly common problem. A controlled trial is required to isolate the contribution of rituximab to the outcomes achieved with this treatment regimen.

Disclosure: All authors have declared no conflicts of interest.