Outcome of Late Antibody Mediated Rejection in Renal Allografts after Conventional and Novel Therapies

Abstract

Background: Antibody-mediated rejection (AMR) often develops early (within days or weeks) after kidney transplantation (txp). However, late AMR, manifesting after 6 months, can also occur. Although several strategies for treating early AMR have been investigated, there is little data on treatment of late AMR. In this study, we present single-center data of 23 patients treated for late AMR. Methods: Patients diagnosed with late AMR between Oct' 09 - Dec '11 were included. Late AMR was diagnosed using Banff 2007 criteria along with presence of donor specific antibody (DSA) and acute rise in serum creatinine (SCr). Patients were treated with plasmapheresis (PP) followed by low dose IVIG +/- rituximab +/- bortezomib. Serial DSA levels were followed throughout and after treatment. A response to therapy was defined as return of SCr to baseline or decline by at least 50% of peak SCr. Histologic improvement and decline in DSA strength were evaluated. Results: Patients' characteristics are presented in the table.Table: [Patients’ Characteristics]Eighteen patients (78%) were treated with PP/low-dose IVIG+rituximab; 9 of them (39%) received 1-3 cycles of bortezomib (4 dose-cycle). Four patients (17%) received PP/IVIG, and 1 received high-dose IVIG only. Patient received a median of 13 (6-22) PP sessions. Only 5 patients (22%) had improvement in all three criteria: histologic, DSA and SCr; 4 of whom had Class I in addition to Class II DSA; 3 of these responders had received bortezomib in addition to PP/IVIG+rituximab. Serious infectious complications required hospital admission developed in 7 patients (30%). There was a significant improvement in mean SCr (p=0.02) after therapy (2.5±1.0mg/dL) compared with SCr at the time of AMR diagnosis (2.9±1.92mg/dL), though in most cases (87%) renal function did not return to baseline. Eight patients (35%) had no improvement in histology and SCr, despite a decline in DSA strength in 5 of them. Lack of response among these patients was associated with higher interstitial fibrosis (ci) score ≥2 (p=0.01) and vascular fibrous intimal thickening (cv) score ≥2 (p=0.02) on index biopsy, but not with SCr at presentation. Conclusion: Reduction in maintenance immunosuppression is highly associated with subsequent late AMR. Our data demonstrate an inadequate response of late AMR to current and novel (bortezomib) therapies used successfully for early AMR. Although the combination of PP/IVIG+rituximab+bortezomib resulted in substantial improvement at least in some patients, the infectious complication risk remained high. The benefits of therapy need to be counterweighed with the potential adverse effects especially in patients with higher biopsy chronicity scores.