ABO-incompatible transplantation without conventional induction immunosuppression (IL-2RB or depleting agents)

Abstract

Transplantation across the ABO blood group (ABOI-Tx) has facilitated to increase in donor pool for living donor kidney transplantation. Increased risk of rejection despite augmented immunosuppression has been the concern for many transplant programs in initiating an ABOI-TX program. The benefits of induction immunosuppression on long-term graft survival in immunologically low-risk individuals are still not clear. Increased immunosuppression of ABOI-Tx recipients before transplantation could provide an opportunity to transplant without induction with IL2-R blockers or Lymphocyte depleting agents. The aim of our study is to analyze the outcome of our series of 25 consecutive ABOI-Tx patients who underwent transplantation without routine thymoglobulin or IL2R-blocker induction. Our study is a prospective observational study for the first 25 consecutive patients who had undergone ABOI-Tx from two tertiary care centers in Kerala, India, having the same IS protocol. Anti-A and anti-B titers ≤1:512 by Gel-method (Biorad) were accepted for desensitization. Patients underwent CDC-crossmatch, Flow-crossmatch, and Luminex-anti-HLA-antibody-screen. Desensitization regimen included- Rituximab 200 mg on Day-21, Triple IS Prednisolone 10 mg, mycophenolate mofetil 1000 mg, and Tacrolimus 0.06 mg/bodywt from Day-14 and Plasma-exchange (PLEX) 3-4 sessions from day -7 to attain titer of 1:8 before transplantation. Transplantation was done without induction IS. Twenty-five patients underwent ABOI-Tx from both centers. Twenty recipients were male. The average age was 34.5 ± 8 years with follow-up of 503 ± 120 days. Eight donors were spouse, 13 were parents and three siblings. The average age of the donor was 46.3 ± 10.5 years. Twenty-two patients have normal functioning transplant with creatinine 1.23 ± 0.2 mg/dL. Kaplan–Meier analysis showed patient survival of 91.2% and death censored graft survival of 95.6% at 36 months. Two patients were lost; one on the postoperative day (POD)-3 due to ACS and second on POD-22 due to sepsis. One graft loss occurred due to posttransplant HUS. Of the functioning 22 allograft-recipients, one had cellular rejection, which resolved with pulse steroids; one developed HUS due to CNI, which recovered with PLEX and switch to non-CNI based IS. One patient developed AMR on POD-4, which was completely reversed with PLEX, intravenous immunoglobulin (IVIG), and augmentation of IS. Three patients had CMV viremia and another three patients had BKV viremia, all resolved with treatment and tailoring of IS. Achieving acceptable anti-A/B titers prior to transplantation is the most critical step in ABOI-Tx. Avoidance of induction IS can reduce cost and infectious complications. Our data showed that there is no increased incidence of rejections in the first post-transplant year for immunologically low-risk individuals from histocompatibility standpoint undergoing ABOI-Tx without induction immunosuppression.