Antibody Mediated Rejection in a Living Donor Kidney Transplant Programme

Abstract

Background: Acute rejection (AR) after transplant is associated with significant reduction in graft half life. With advent of newer immunosuppressive drugs, the incidence of acute rejection has decreased worldwide, but antibody mediated rejection (AMR) remains an important cause of graft loss. We analyzed spectrum of acute AMR and their short term outcomes at our centre. Methods: We analyzed 264 patients, transplanted between Feb 2010 and Oct 2011 who had at least 3 months of follow up. Immunosuppressive protocols were- TAC+MMF+ST in 169/264 (64%) patients, steroid free (SF) protocol (Induction+TAC+MMF) in 76/264 (29%), TAC+AZA+ST in 16/264 (6%) and CYC+MMF+ST in 3 (1.2%) patients with HCV infection. In SF group, 4/76 received ATG induction and rest received basiliximab as induction. In steroid group 63/187 (23.8%) patients received basiliximab induction and 8 patients who were second or third transplant (1 patient) received ATG as induction. NIH CDC cross match was negative in all patients prior to transplantation. Tacrolimus levels were done routinely and graft biopsy was done whenever rejection was suspected. The AMR was defined according to Banff 97 classification, i.e.- presense of 2/3 criteia-.presense of donor specific antibody (DSA), C4d positivity on IF and light microscopic features of AMR. Target trough level of tacrolimus was kept between 8-12 ng/ml for first three months, 6-8 ng/ml for next 3-6 months and 4-6 ng/ml thereafter. Outcomes were evaluated in terms of acute rejection, reversal of rejection with treatment and graft or patient loss. Results: 203/264 patients (76.8%) were males. The mean age was 40.5 (±13) years. The mean duration of follow up was 290 (±110.) days. 36/264 (13.6%) developed AR, of which 31/36 (86%) were biopsy proven (BPAR). 7/264 (2.6%) had AMR (22.5% of BPAR), 6 of these were in steroid group, 5 of them developed rejection within 4-5 days and they received thymoglobulin, plasmapheresis (PP), and intravenous immunoglobulins(IV Ig), however graft nephrectomy had to be done in 3/5 as they did not respond and there was infarction in grafts on repeat biopsy. Two patients responded completely. Two of these patients had positive DSA after transplant. However one of them later on developed chronic AMR. The sixth patient in steroid group had AMR at 7 months and had incomplete response. The only patient in steroid free group developed rejection 6 months after transplant and responded completely with same regimen. This patient later on developed chest infection and died. In three patients with graft nephrectomy, one patient received multiple blood transfusions, one patient had SLE and third patient had historic B cell cross match positivity. Overall graft survival was 96.2% and patient survival was 98.1%. Conclusions: AMR remains an important cause of resistant rejections and graft loss. More sensitive cross match tecniques might help to identify the high risk patients.