© 2014 Lippincott Williams & Wilkins. Background. Incompatible live donor kidney transplantation is associated with an increased rate of antibodymediated rejection (AMR) and subsequent transplant glomerulopathy. For patients with severe, oliguric AMR, graft loss is inevitable without timely intervention. Methods. We reviewed our experience rescuing kidney allografts with this severe AMR phenotype by using splenectomy alone (n=14), eculizumab alone (n=5), or splenectomy plus eculizumab (n=5), in addition to plasmapheresis. Results. The study population was 267 consecutive patients with donor-specific antibody undergoing desensitization. In the first 3 weeks after transplantation (median=6 days), 24 patients developed sudden onset oliguria and rapidly rising serum creatinine with marked rebound of donor-specific antibody, and a biopsy that showed features of AMR. At a median follow-up of 533 days, 4 of 14 splenectomy-alone patients experienced graft loss (median=320 days), compared to four of five eculizumab-alone patients with graft failure (median=95 days). No patients treated with splenectomy plus eculizumab experienced graft loss. There was more chronic glomerulopathy in the splenectomyalone and eculizumab-alone groups at 1 year, whereas splenectomy plus eculizumab patients had almost no transplant glomerulopathy. Conclusion. These data suggest that for patients manifesting early severe AMR, splenectomy plus eculizumab may provide an effective intervention for rescuing and preserving allograft function.