Use of anti-CD20 antibody in the treatment of post-transplant glomerulonephritis.

Post-transplant glomerulonephritis (PTGN) accounts for 4-10% of late graft loss. Six consecutive patients who developed PTGN 3-72 months post-transplant presented to our center with deteriorating kidney function and proteinuria. Three had focal segmental glomerulosclerosis; one had membranoproliferative glomerulonephritis Type 1; one recurrent membranous nephropathy; and one recurrent immunoglobin A nephropathy. All six were treated with an aggressive immunosuppression regimen including rituximab, pulse steroids and/or maximization of mycophenolic acid and calcineurin inhibitor therapy. Four of the six patients received plasma exchange. The patients were followed for a minimum of nine months after treatment. Proteinuria decreased from 7.2 ± 4.4 to 1.4 ± 1.5g (p = 0.04), while mean estimated glomerular filtration rate was 31.2 ± 13.1 and 42.5 ± 21.7 mL/min (p = 0.07) at nine months. No adverse events were noted. These observations suggest that immune modulating therapy may be of benefit in the treatment of PTGN.

Cross Reactive Epitope Group antibodies in sensitized kidneys transplant recipients was associated with early acute Antibody Mediated Rejection.

BACKGROUND: Antibody Mediated Rejection (AMR) is a major cause of early graft loss, graft dysfunction, and chronic allograft nephropathy. Patients with elevated pre-transplant Panel Reactive Antibodies (PRA) are at much higher risk to develop AMR. We, retrospectively, studied the attack rate of AMR in sensitized recipients and evaluated whether preformed antibodies to donor Cross Reactive Epitope Group (CREG) and/or choice of induction immunosuppressive agent affected the frequency of this complication. METHODS: From the period between September 2002 and March 2008, we identified 19 sensitized renal transplant recipients (with mean PRA of 44.5+/-26%) and recorded the induction agent, number of HLA antigen mismatches, CREG match, CREG antibodies, PRA levels, clinical course, biopsy proven rejection episodes and presence of donor specific antibody. Nine patients were induced with Alemtuzumab (Campath-1H) and ten received horse or rabbit derived polyclonal antithymocyte antibody ATGAM (Pharmacia) or Thymoglobulin (Genzyme). All recipients were cross-match negative at time of transplant. RESULTS: Out of the 19 patients, 9 patients developed acute rejection (47.4%), 4 had AMR and 5 had Acute Cellular Rejection (ACR). Out of 19 patients, 9 patients had existing CREG antibodies (as per CREG Model proposed by McKenna, Takemoto et al.). All patients who developed AMR were found of have preformed antibodies to donor CREG. The median time interval for the development of acute humoral rejection was only 6 days and biopsies showed acute vascular rejection with Complement (C(4)D) deposition. CONCLUSIONS: Pre-existing CREG antibodies in sensitized renal transplant patients appear to identify a group at high risk to develop AMR.