Although most protocols for ABO-incompatible kidney transplantation have employed splenectomy, its utility is unproven. The aim of the current study was to compare the outcomes of ABO-incompatible living donor kidney transplantation with splenectomy versus a protocol involving intensive posttransplant antibody monitoring to maintain low levels of antiblood group antibody.
We retrospectively studied all ABO-incompatible living donor kidney transplants at our institution between September 1999 and November 2004 (n=34). Prior to May 2003, all patients were included in a protocol involving pretransplant plasmapheresis and splenectomy at the time of transplant (n=23). After May 2003, splenectomy was not performed and a protocol that involved pretransplant anti-CD20 antibody and a more intensive posttransplant plasmapheresis regiment aimed at maintaining low levels of antiblood group antibody during the first 2 weeks following transplantation was utilized (n=11).
Patient and graft survival was similar in the two groups. Humoral rejection occurred in 18% nonsplenectomized and 30% of splenectomized patients (P=0.68). Humoral rejection correlated with the baseline antibody titer in both groups. Individuals with elevated baseline antibody titer (> or =1:256) appear to be at high risk for humoral rejection regardless of protocol used. Antiblood group antibody levels 3 and 12 months after transplantation were similar in both groups.
Splenectomy is not essential for successful ABO-incompatible kidney transplantation, although individuals with high baseline antidonor blood group antibody titers are at high risk for humoral rejection. The use of intensive posttransplant monitoring may help prevent antibody-mediated graft damage.
"Titers of the anti-A/B IgG antibodies are considered to be more important than titers of IgM. Gloor et al. reported that initial anti-A/B IgG titer of more than 1:256 is significantly associated with the incidence of antibody-mediated rejection . Further, Toki et al. reported that an anti-A/B IgG titer above 1:32 at the time of transplantation is an independent risk factor for antibody-mediated rejection . "
[Show abstract][Hide abstract] ABSTRACT: In 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.
In 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.
Anti-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.
With 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.
Annals of Laboratory Medicine 07/2012; 32(4):283-8. DOI:10.3343/alm.2012.32.4.283 · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rituximab, a monoclonal antibody directed against the CD20 molecule found on pre-B cells and mature B cells (but not on plasma cells), was introduced in the late 1990s for the treatment of non-Hodgkin's lymphoma. Recently, this antibody has been used to treat autoimmune diseases, especially those associated with a prominent humoral component and with potentially pathogenic autoantibodies. Small cohort studies have indicated that rituximab could have an important role in the management of these disorders. Rituximab has also been utilized in the transplant setting, to diminish levels of alloreactive antibodies in highly sensitized patients, to manage ABO-incompatible transplants, and to treat rejection associated with B cells and antibodies. The exact mechanism by which rituximab exerts its effects in autoimmunity and transplantation remains unclear, as specific autoantibody or alloantibody levels often seem not to diminish in parallel with clinical improvement. A role for rituximab in depleting B cells and compromising their antigen-presenting function seems likely; rituximab might also inhibit T-cell activation. A synergistic effect has been noted in vitro following administration of corticosteroids to B-cell lines, with accentuation of B-cell cytotoxicity; this observation might be relevant to certain studies, as some regimens have utilized both agents simultaneously. This article reviews the current use of rituximab in renal disease and transplantation, and includes discussion of the drug's potential role in novel therapeutic protocols.
[Show abstract][Hide abstract] ABSTRACT: Over the past several years, protocols have been developed to allow patients with antibody against either donor blood group (ABO-incompatible) or donor HLA antigens (positive cross-match) to undergo successful kidney transplantation. Important factors determining the development of hyperacute rejection, humoral rejection and long-term graft survival have been defined. In this review, the clinical experience with ABO-incompatible and positive cross-match kidney transplantation at Mayo Clinic, Rochester are described with an emphasis on both patient management issues and gaps in our current knowledge in this emerging field.
International Congress Series 07/2006; 1292:113-119. DOI:10.1016/j.ics.2006.03.057
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