EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: The best treatment for end-stage renal disease is kidney transplant, but the shortage of donor organs has caused long waiting times for an appropriate organ allograft. The use of ABO-incompatible kidney transplant can be a valuable option to expand the donor pool. The purpose of the present study was to evaluate 13 patients who had successful ABO-incompatible kidney transplant with double-filtration plasmapheresis and rituximab.

Materials and Methods: From January 2011 to August 2012, there were 13 patients who had ABO-incompatible kidney transplant. Antibody titers were monitored during preconditioning and after transplant. Preconditioning protocol included rituximab, mycophenolate mofetil, tacrolimus, corticosteroids, double-filtration plasmapheresis, and intravenous immunoglobulin.

Results: There were no episodes of acute T-cell or antibody-mediated rejection. There were no surgical complications except postoperative bleeding in 1 patient. Mean serum creatinine at 2 weeks after transplant was 71 ± 18 μmol/L (0.8 ± 0.2 mg/dL). At mean follow-up 267 days (range, 1-19 mo), there was no graft loss or patient death.

Conclusions: The ABO-incompatible kidney transplants were successful after the preconditioning protocol that included double-filtration plasmapheresis and rituximab. The use of ABO-incompatible kidney transplant may increase the availability of kidney transplant and avoid or shorten dialysis. Future multicenter studies are justified to develop a standardized preconditioning protocol.

Key words : End-stage renal disease, Preconditioning, Rejection, Treatment

The best treatment for end-stage renal disease is kidney transplant, but the shortage of donor organs has caused long waiting times for an appropriate organ allograft.¹ The use of ABO-incompatible transplant can be a valuable option to expand the donor pool. For many years, ABO-incompatible kidney transplant was considered contraindicated, and there was concern that presence of antibodies against blood group antigens may cause a higher frequency of acute antibody-mediated rejection, graft loss, or death.²

In 1987, ABO-incompatible kidney transplant was reported with a desensitization protocol that included splenectomy.³ Since 1989, ABO-incompatible kidney transplant has become accepted in Japan as a therapeutic alternative for end-stage renal disease.^4-6Several preconditioning methods have been used including plasmapheresis, intravenous immuno-globulin, thymoglobulin induction, and anti-CD20 antibodies (rituximab), but there is no standardized preconditioning protocol available.⁷

The purpose of the present study was to evaluate 13 patients who had successful ABO-incompatible kidney transplant with double-filtration plasmapheresis and rituximab.

Materials and Methods

From January 2011 to August 2012, a total of 102 recipients had kidney transplant, 60 from living donors and 42 from deceated donors in Keimyung University Dongsan Hospital. There were 13 patients (21% of living donor transplant) who had ABO-incompatible kidney transplant. Preconditioning protocol included rituximab (200 mg/m²) and mycophenolate mofetil (body weight > 60 kg, 2.0 g/d; body weight < 60 kg, 1.5 g/d) given at 2 weeks before transplant (Figure 1). In addition, tacrolimus (0.1 mg/kg/d) and corticosteroids (0.5 mg/kg/d) were started 10 days before the operation. Double-filtration plasmapheresis (Plasauto EZ, Asahi Kasei Medical, Tokyo, Japan) was started 10 days before transplant and was performed until anti-A or anti-B antibody titer was < 1:8. The processed plasma was 1.5 or 2 total plasma volumes, and replacement included 250 mL of 5% human albumin and 0.9% normal saline. At the final plasmapheresis session before transplant, plasma exchange was performed with fresh frozen plasma (AB blood group). Intravenous immunoglobulin (100 mg/kg) was given after each double-filtration plasmapheresis session (Figure 1). Baxiliximab was given at operation day and 4 days after transplant as induction. After transplant, the anti-ABO antibody titer was monitored weekly. Posttransplant plasmapheresis was indicated to eliminate the rebounding antibody level when posttransplant anti-ABO antibody titer was > 1:8 during the first week or > 1:16 during the second week.

There were 13 ABO-incompatible kidney transplants performed (Table 1 and 2). In the 13 transplants, donor and recipient blood group types were donor type B to recipient type A (4 transplants), A to O (3 transplants), B to O (2 transplants), AB to B (2 transplants), AB to A (1 transplant), and A to B (1 transplant). There were 12 primary transplants and 1 revision transplant. Mean initial ABO antibody titer (immunoglobulin G) before plasmapheresis was 1:42 (range, 1:2 to 1:128) and patients had mean 3.9 pretransplant double-filtration plasmapheresis sessions. Double-filtration plasmapheresis was not performed in patents who had a low ABO antibody titer (< 1:2). The pretransplant mean ABO antibody titer (immunoglobulin G) was 1:2 (range, 1:1 to 1:8). There were no episodes of acute T-cell or antibody-mediated rejection. No additional plasmapheresis was performed after transplant. There were no surgical complications except postoperative bleeding that necessitated transfusion in patient No. 1. Mean serum creatinine at 2 weeks after transplant was 71 ± 18 μmol/L (0.8 ± 0.2 mg/dL). At mean follow-up 267 days (range, 1-19 mo), there was no graft loss or patient death.

There were 2 patients who had special situations. Patient No. 5 had ABO-incompatible kidney trans-plant without double-filtration plasmapheresis because her preoperative anti-ABO antibody titer was 1:1. Patient No. 7 was highly sensitized, and his first kidney transplant in October 2004 was complicated by graft failure after 4 years; the revision kidney transplant was an ABO-incompatible transplant, and preoperative panel reactive antibody was 80%. Both patients had successful ABO-incompatible kidney transplant without rejection or complications.

In the past, ABO-incompatible kidney transplant was an absolute contraindication for organ transplant.² However, the frequency of ABO-incompatible kidney transplant has increased because of improved understanding and treatment of immunologic factors.⁸ During preconditioning, the isoagglutinin titer against the donor was a major factor for rejection, and an antibody depletion technique was used.⁹ We used double-filtration plasmapheresis because this is a safe and effective method, no coagulation factors are eliminated, and large plasma volumes may be passed.¹⁰ In the present study, double-filtration plasmapheresis was effective at decreasing the ABO antibody titer (immunoglobulin G) before transplant. When the recipient’s blood group antibody titer was low, no pretransplant antibody-reducing regimen was used, and this approach has been effective.

There are no standardized preconditioning protocols available, and many transplant centers have used their own independent desensitization protocols.¹¹ In the present study, we used rituximab, double-filtration plasmapheresis, low-dose intra-venous immunoglobulin, and immunosuppression with tacrolimus and mycophenolate mofetil. The present results were limited because the long-term outcome of ABO-incompatible kidney transplant is unknown, but we showed that ABO-incompatible kidney transplant can be performed successfully after a preconditioning protocol. The use of ABO-incompatible kidney transplant may increase the availability of kidney transplant and avoid or shorten dialysis. Future multicenter studies are justified to develop a standardized preconditioning protocol.

Volume: 12 Issue: 5 October 2014

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