Outcomes Of ABO-incompatible Kidney Transplantation Research Articles

ABO-incompatible kidney transplantation

A dramatic shortage of available organs around the world encouraged attempts to cross previously forbidden immunological boundaries in kidney transplantation. This review focuses on the recent results of ABO-incompatible kidney transplantation. The outcome of ABO-incompatible kidney transplantation in terms of patient and graft survival is comparable to ABO-compatible transplantation for adult and pediatric recipients. Splenectomy has been replaced by the B-cell-depleting agent rituximab to avoid isoagglutinin titer rebound, prevent antibody-mediated rejection, and improve graft survival. However, the risk for infections may be increased and warrants caution. Corticosteroids remain a necessary component of any ABO-incompatible protocol; early as well as late steroid withdrawal may bear an enhanced risk for acute rejection and should only be performed with careful follow-up including protocol biopsies. The few studies that have long-term outcomes using protocol biopsies have characterized a state of accommodation by up-regulation of complement inhibitors, down-regulation of A/B antigens, and establishment of endothelial chimerism over time. The experience accumulated around the world indicates that ABO-incompatible kidney transplantation is well tolerated and effective in adults and in children, and it represents an important step forward in expanding the living donor pool. Further understanding of ABO-incompatible graft accommodation may have broader implication also for human leukocyte antigen-sensitized allograft recipients.

Role of Plasma Exchange in ABO-incompatible Kidney Transplantation

BackgroundIn the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However, multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection. In this study, we determined the usefulness of plasma exchange (PE) for removing anti-A/B antibodies that cause hyperacute/acute humoral graft rejection in patients undergoing ABO-incompatible kidney transplantation.MethodsIn our study, 12 patients underwent ABO-incompatible kidney transplantation. All recipients received pre-transplantation conditioning by PE or intravenous immunoglobulin (IVIG) administration. After pre-transplantation conditioning, anti-A/B antibody titers were evaluated, and transplantation was performed when the titer was below 1:8. To assess the transplantation outcome, anti-A/B antibody titers, creatinine level, estimated glomerular filtration rate (eGFR), and proteinuria levels were measured.ResultsAnti-A/B antibody titers were below 1:8 in all patients at the time of transplantation. eGFR measured on post-transplant day 14 showed that 10 patients had immediate recovery of graft function, while 2 patients had slow recovery of graft function. Short-term outcomes of ABO-incompatible kidney transplantation (measured as creatinine levels) after reducing anti-A/B antibody titers were similar to those of ABO-compatible kidney transplantation. After transplantation, the anti-A/B antibody titers were below 1:8 in 7 patients, but the remaining 5 patients required post-transplantation PE and IVIG treatment to prevent antigen-antibody reactions.ConclusionsWith the increasing demand for kidney donations, interest in overcoming the ABO incompatibility barrier has increased. PE may be an important breakthrough in increasing the availability of kidneys for transplantation.

Excellent Outcomes of ABO-Incompatible Kidney Transplantation: A Single-Center Experience

IntroductionDue to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved; the rates of graft survival among these patients are currently similar to those of recipients of ABO-compatible grafts. Our single-center experience describing the immunosuppressive protocols, complications, and grafts survivals is documented in this study. Patients and MethodsAmong 123 patients with end-stage renal disease who underwent living donor kidney transplantation between January 1999 and December 2010, 25 cases were ABO-incompatible grafts. All of these patients were followed until August 2011. Analyzing these patients, we focused on their immunosuppressive protocols, complications, and graft survivals. ResultsPatient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and an intractable acute cellular rejection episode, 1 patient an antibody-mediated rejection, and 6 patients had acute cellular rejection episodes. However, there were no severe complications. ConclusionAlthough ABO-incompatible kidney transplantation is a high-risk procedure, a short-term graft survival rate of 100% may be expected due to recent significant improvements in desensitization and recipient management.

The 5-Year Outcome of ABO-Incompatible Kidney Transplantation With Rituximab Induction

In 2002, we introduced the anti-CD20 chimeric antibody, rituximab, for ABO-incompatible kidney transplantation (ABO-IKT). Here, we report the 5-year outcome obtained using rituximab as part of the preoperative regimen for ABO-IKT. Between January 2002 and December 2008, 408 patients underwent living-related kidney transplantation at our department. The patients were divided into three groups: group A (n=280), ABO-compatible kidney transplantation (ABO-CKT); group B (n=63), ABO-IKT without rituximab induction; and group C (n=50), ABO-IKT with rituximab induction. Basic immunosuppression was the same in all three groups except for the use of rituximab, which was administered at 100 mg (n=6), 200 mg (n=26), and 500 to 1000 mg (n=18). The graft survival rates in groups A, B, and C were 99.2%, 96.8%, and 100% at 1 year, 93.8%, 94.9%, and 100% at 3 years, and 88.4%, 90.3%, and 100% at 5 years after transplantation, respectively. Serum creatinine levels in the three groups were not different at 1, 3, and 5 years after transplantation. The numbers of episodes of acute antibody-mediated rejection in groups A, B, and C were 7 (2.5%), 10 (15.9%), and 2 (4.0%), respectively (P=0.651), and acute cellular rejection was observed in 40 (14.3%), 6 (9.5%), and 2 (4.0%) patients, respectively (P=0.0957). There was no increased risk of cytomegalovirus infection in group C. In the long term, inclusion of rituximab in the preoperative regimen yielded an even better outcome than that of ABO-CKT and rituximab-untreated ABO-IKT, without any increase in the risk of infection.

ABO-incompatible kidney transplantation in Japan

Up to 2005, the number of patients on dialysis therapy exceeded more than 250,000 in Japan; however, only 200 deceased and 800 living kidney transplants have been performed annually. We have been making continuous efforts in ABO-incompatible kidney transplantation since 1989 to expand the opportunities for living kidney transplantation in Japan. From the Japanese registry, we have reviewed the long-term patient and graft outcome of ABO-incompatible kidney transplantation. This survey focused on 685 patients who received ABO-incompatible kidney grafts from January 1989 to December 2004 in whom monitoring follow-up could be achieved in 75 institutions. The overall patient survival rates at 1, 3, 5 and 10 years after transplantation were 94%, 91%, 87% and 82%, with overall graft survival rates of 87%, 83%, 76% and 57%, respectively. The graft survival rate was significantly higher in patients aged 29 and younger compared with those aged 30 and older. Especially in children aged 15 and younger, they have shown excellent graft survival rate. The patients with anticoagulation therapy showed significantly higher graft survival rate than those without anticoagulation. There were no significant differences between A- and B-incompatibility with respect to clinical outcomes. There were also no significant difference in numbers of HLA mismatches, induction and maintenance calcinurine inhibitors (ciclosporine vs. tacrolimus) and donor/recipient relationships with respect to the outcomes. A result of most recent 245 cases since 2001 had dramatically improved with 1-year graft survival is 96% and there is a significant difference between the groups in 2001 onwards and before. This study confirms that the outcome of ABO-incompatible living kidney transplantation in Japan is excellent and is similar to that in ABO-compatible cases. ABO-incompatible kidney transplantation has already become one of a standard, safety and effective treatment choice for end-stage renal disease.

Excellent long-term outcomes of ABO-incompatible kidney transplantation in children

Due to profound shortage of suitable deceased allografts, much effort has been made to investigate whether successful kidney transplantation is possible across the ABO blood group barrier even for pediatric recipients. Methods Twenty-five pediatric patients underwent ABO-incompatible living kidney transplantation. All patients received three sessions of plasmapheresis (PP) or immunoadsorption (IA) to remove the anti-A/B antibodies before transplantation. This was followed by splenectomy and a conventional quadruple drug immunosuppressive protocol. To prevent overwhelming postsplenectomy infections, penicillin prophylaxis as well as pretransplant pneumococcal vaccine was given to all patients. Results Of 25 patients, 12 grafts had rebound increases in their anti-A/B isoagglutinin titers within 10 days posttransplant. Moreover, 10 of 12 (83%) patients developed acute rejection with the increase of isoagglutinins. One patient lost the graft because of uncontrolled delayed hyperacute rejection, while the other nine acute rejection episodes were reversed with a standard anti-rejection therapy in combination with PP/IA. Four patients had severe bacterial infectious complications after transplantation. The actuarial 1-, 5- and 10-year graft survival rates are 96%, 91% and 91%, respectively. Conclusions With the adequate desensitization protocol, ABO-incompatible kidney transplantation is a valid alternative even for children with end stage renal disease.

Efficacy of basiliximab induction therapy in ABO-incompatible kidney transplantation: A rapid steroid withdrawal protocol

Introduction We have performed ABO-incompatible (ABO-i) kidney transplantation (KT) to alleviate the severe organ shortage in our country. Induction therapy with basiliximab, a monoclonal anti-interleukin-2 receptor antibody, is known to be effective in reducing the incidence of acute rejection (AR) after ABO-compatible KT. However, the efficacy of basiliximab in ABO-i KT is still unknown. In this study, we evaluated the effect of basiliximab to decrease overall maintenance immunosuppression (a steroid withdrawal protocol) and to improve the outcome of ABO-i KT. Patients and methods Between April 2002 and May 2003, 14 adult patients underwent ABO-i KT from living donors with cyclosporine (CsA)-based immunosuppression. There were seven men and seven women of mean age 48 ± 10 years. Three of the 12 cases were second KT. Three sessions of plasmapheresis were performed to remove anti-AB antibodies before KT. Splenectomy was performed in all patients. Immunosuppression consisted of methylprednisolone (MP), CsA, and mycophenolate mofetil, in addition to antibody induction with basiliximab. MP was completely withdrawn on postoperative day 14. Results In 3 of 14 recipients, MP was restarted because of AR or a suspicion of AR. Both patient and graft survivals were 100%. The incidence of biopsy-proven AR was 14% (2/14). There was no adverse effect related to the antibody therapy. Conclusion The use of basiliximab induction therapy may eliminate the need for steroid maintenance therapy without increasing AR risk, even among ABO-i KT recipients. We conclude that basiliximab provides safe and effective induction immunosuppression in ABO-i KT recipients.

1946: Excellent Outcome of Abo-Incompatible Kidney Transplantation Under Pretransplant Immunosuppression with Tacrolimus, Mycophenolate Mofetil, and Steroid

1946: Excellent Outcome of Abo-Incompatible Kidney Transplantation Under Pretransplant Immunosuppression with Tacrolimus, Mycophenolate Mofetil, and Steroid