Prospective Post-Transplant DSA Monitoring in Kidney Transplant Recipients With Pre-Transplant DSA and a Positive Crossmatch Treated With IVIG/Rituximab.

Abstract

Purpose: Desensitization with IVIG/Rituximab allows acceptable graft survival in sensitized kidney transplant recipients (KTR) with pre-transplant (pre-tx) donor-specific antibody (DSA) and a positive cross-match (XM+). We report initial data from a 3-yr prospective study of DSA monitoring in DSA+/XM+ living donor (LD) KTR to assess the efficacy of antibody removal with IVIG/Ritux and possible associations between pre-tx DSA-MFI and C1q with post-transplant outcomes. Methods: Prospective DSA monitoring with Single Antigen Luminex assay was performed in DSA+/XM+ (flow titer <1:32) LD KTR. All KTR received IVIG (2 gms/kg on days -7 and +7), rituximab (375 mg/m2 day +1), alemtuzumab (30 mg day 0), and maintenance tac/MMF/Pred. C1q binding assay was performed on pre-tx sera. Data were analyzed using paired t-tests and linear regression. Results: From 11/09-10/13, 23 DSA+/XM+ LD KTR were enrolled. Patient survival is 100% and graft survival is 96%. 3 pts (13%) had acute rejection (2/3 C4d+) at 4, 12, and 19 mos. A total of 42 DSAs were identified in 23 KTR (range 1-5 DSA/pt). Mean±SD pre-IVIG MFI was 4191+4166. 8/23 pts had positive C1q assay (>500) against donor HLA in pre-IVIG serum. We found a significant reduction from pre-IVIG MFI to post-IVIG/pre-tx MFI (p=0.030) and to 1 mo post-tx MFI (p=0.005). The magnitude of IVIG MFI pre-IVIG appears related to decrease in MFI both post-IVIG/pre-tx (beta=-0.627, p<0.001) and at 1 month post tx (Figure). Durability of DSA reduction over 36 months awaits further follow-up. Due to low incidence of AR, correlation between either pre-IVIG MFI or C1q binding or magnitude of reduction post IVIG/Ritux and subsequent AR or graft loss await longer follow-up.Figure: No Caption available.Conclusion: Desensitization with IVIG/Ritux results in excellent short-term patient and graft survival with low AR in LD KTR with DSA/+XM. There is a significant reduction of DSA 1 month post-tx and the magnitude of early MFI reduction is related to pre-treatment level. Longer follow-up is needed to determine durability of DSA removal and impact on long-term AR or graft survival. DISCLOSURE:Shaffer, D.: Grant/Research Support, Novartis, Astellas.