Study 1: characterization of acute rejection episodes after pre-emptive plasmapheresis and cytomegalovirus hyperimmune globulin to abrogate a positive crossmatch and allow live donor renal transplantation

Abstract

P atients who undergo desensitization protocols to allow renal transplantation despite a positive crossmatch to their living donor remain at risk for acute rejection, specifically, antibody-mediated rejection. Our center uses plasmapheresis and cytomegalovirus hyperimmune globulin (PP-CMVIg) to precondition such patients. In this study, we seek to identify those patients at highest risk for antibodymediated rejection, allowing future modifications to decrease the incidence of acute rejection. All 33 patients treated with PP-CMVIg before live donor renal transplant (Feb 1998–Oct 2002) were analyzed. Episodes of acute rejection were confirmed by biopsy. Diagnostic criteria for antibody-mediated rejection included compatible histologic findings, positive C4d immunohistochemical results, and rising donor-specific antibody titer. Acute rejection occurred in 21 of 33 patients (64%), at a median of 9 days after transplantation, and 12 of 21 were diagnosed with antibody-mediated rejection. Antibody-mediated rejection was treated with steroids and additional PP-CMVIg treatments (mean, 4.3); steroids with or without antilymphocyte therapy were used to treat the 9 other cases of acute cellular rejection. Three patients sustained graft loss, as follows: 1 noncompliance, 1 hemolytic uremic syndrome, and 1 associated with patient death from surgical complications. Patients with an initially positive cytotoxic crossmatch (vs flow, P .007), a positive cytotoxic crossmatch at transplant (vs negative, P .032), and patients who required 6 pretransplant PP-CMVIg treatments (P 0.012) had a higher risk of acute rejection. Occurrence of acute rejection was associated with a longer length of stay (16 vs 5 days, P .0001) and lower 1-week creatinine clearance (43 vs 65 mL/min, P .01). Patients who had an episode of acute rejection had no significant change in their current creatinine clearance (75 vs 73 mL/min at 16 months’ mean follow-up, P .9). Patients with antibody-mediated rejection did not have significantly different outcomes compared with those with cellular rejection alone. Intensity of C4d and donor-specific antibody titer did not predict graft function. Donor-specific antibody remains undetectable in 28 of 30 patients with a functioning allograft. Conclusions: Patients receiving PP-CMVIg to abrogate a positive crossmatch are at risk for acute rejection, especially antibody-mediated rejection, but are responsive to additional PP-CMVIg. Acute rejection does not have an impact on graft function at 1 year. Patients with high levels of donor-specific antibody, as evidenced by an initially positive cytotoxic crossmatch, a positive cytotoxic crossmatch at the time of transplantation, and a requirement of more pretransplant PP-CMVIg treatments, are at highest risk for antibody-mediated rejection and require vigilant observation during the first 2 weeks after transplantation. From the Departments of Surgery, Medicine, and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.002