ABO-incompatible live donor renal transplantation using blood group A/B carbohydrate antigen immunoadsorption and anti-CD20 antibody treatment

Background:Blood group ABO-incompatible live donor (LD) renal transplantation may provide a significant source of organs. We report the results of our first 14 cases of ABO-incompatible LD renal transplantation using specific anti-A/B antibody (Ab) immunoadsorption (IA) and anti-CD20 monoclonal Ab (mAb) treatment. Patients and treatment protocol:Recipients were blood group O (n=12), A (n=1) and B (n=1). Donors were A(1) (n=2), A(2) (n=3), A(2)B (n=1) and B (n=8), and all were secretor positive. Anti-human leukocyte antigen (HLA) Ab panel reactivity was negative in all recipients except one. All recipients were pre-treated with 3 to 6 IA sessions, using A or B carbohydrate antigen columns, until their anti-A(1)/B RBC panel indirect antiglobulin test (IAT) titers were <= 8. CDC crossmatch was negative in all cases. Recipients received preoperative mycophenolic acid, and steroids/tacrolimus were started at transplantation. No splenectomy was performed. Eight recipients received one dose of anti-CD20 mAb (rituximab, 375 mg/m(2)) pre-operatively and 11 recipients had postoperative protocol IA. Results:In the initial protocol, anti-CD20 mAbs were used only for recipients receiving A(1) grafts. One B graft (HLA-identical donor, 84% panel reactivity) was lost in a severe anti-B Ab-mediated acute rejection. Subsequently, the protocol included anti-CD20 for recipients of both A(1) and B grafts and postoperative protocol IA to all recipients. The subsequent 10 grafts had excellent function, giving a total graft survival of 13/14 (observation range 2 to 41 months). At 1 yr, mean serum creatinine was 113 mu mol/l (n=8) and mean glomerular filtration rate was 55 ml/min/1.73 m(2) (range 24 to 77). In the remaining five cases, with less than 1 yr follow up, mean serum creatinine was 145 mu mol/l at 2 to 9 months follow up. Pre-IA anti-A/B titers were in the range of 2 to 32 (NaCl technique) and 16 to 512 (IAT). More than 90 IA sessions were performed in 14 recipients without any significant side effects. Recipient anti-A/B titers returned after transplantation to pre-IA levels or slightly lower. Postoperative renal biopsies were performed in 10 patients. In the 13 patients with long-term function, one patient experienced cellular rejection (Banff IIB) at 3 months without anti-B titer rise. This rejection was concomitant with low tacrolimus plasma levels and was easily reversed by steroids. In 8 of 10 cases, C4d staining was positive in peritubular capillaries. Conclusion:Blood group ABO-incompatible LD renal transplantation using A and B carbohydrate-specific IA and anti-CD20 mAbs has excellent graft survival and function.