Outcome of desensitization in human leukocyte antigen- and ABO-incompatible living donor kidney transplantation: a single-center experience in more than 100 patients.

Antibody-mediated rejection (AMR) and inferior graft outcome remain the 2 most important obstacles to successful kidney transplantation in human leukocyte antigen (HLA)- and ABO-incompatible recipients. We report a single-center experience in the outcome of desensitized living donor HLA- and ABO-incompatible kidney transplantation. Since 2007 we included 2 groups in our desensitization program. HLA-incompatible living donor kidney transplant candidates displaying donor-specific antibodies (DSA) with or without a positive T-cell and/or B-cell flow crossmatch (FCXM). Second, those displaying DSA with positive T-cell immunoglobulin (Ig)G AHG CDC CXM with a titer of ≤1:8, as well as all ABO-incompatible living donor kidney transplant candidates with an IgM isoagglutinin titer ≤ 256. They were risk stratified for AMR and underwent individualized desensitization protocol: ABO-incompatible and HLA-incompatible candidates with either positive AHG CDC CXM or positive T and/or B IgG flow CXM with repeat HLA mismatch from a previous transplantation were deemed to be high risk and received a single dose of Rituximab, therapeutic plasma exchange and high-dose intravenous immunoglobulin (IVIG) (2 g/kg). HLA-incompatible candidates with negative CDC but positive T and/or B IgG FCXM were deemed intermediate risk, receiving rituximab and high-dose IVIG. Those with positive DSA but negative flow and CDC CXM were deemed low risk, receiving low-dose IVIG (1 g/kg). All patients received induction with thymoglobulin and were maintained on a tacrolimus-based immunosuppressive regimen. Among 124 incompatible recipients, 85 received HLA-incompatible and 39 ABO-incompatible living donor kidney transplantations after desensitization. Risk stratification for HLA-incompatible transplants revealed 61 high-risk, 42 intermediate-risk, and 21 low-risk cases. Ninety-nine (80%) were primary transplants. At a median follow-up of 23 (range 1-53) months, patient survival was 98% and death censored graft survival 96%. Mean serum creatinine was 84 μmol/L (range 41-169). Acute cellular rejection was observed in 15 (12%) and AMR in 5 (4%) patients. All rejection episodes responded to treatment except 1 AMR in an ABO-incompatible transplant that led to graft failure. Our risk stratification for desensitization strategy achieved a low incidence of AMR among HLA- and ABO-incompatible kidney transplant recipients. Their 2-year data appear to be comparable to HLA- and ABO-compatible transplantations.

Al Meshari K ，Pall A ，Chaballout A ，El Gamal H ，Al Mana H ，Humaidan H ，Alzayer F ，Al Talhi M ... -  《-》

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

Nordén G ，Briggs D ，Cockwell P ，Lipkin G ，Mjörnstedt L ，Mölne J ，Ready A ，Rydberg L ，Samuelsson O ，Svalander CT ，Breimer ME ... -  《xenotransplantation》

Frequent development of subclinical chronic antibody-mediated rejection within 1 year after renal transplantation with pre-transplant positive donor-specific antibodies and negative CDC crossmatches.

Although short-term graft survival has been improved by recent desensitization protocols including B cell depletion therapy, little is known about risk factors of chronic antibody-mediated rejection (CAMR) in HLA-incompatible (HLA-I) renal transplantation (RTx). Twenty-six HLA-I RTx with positive donor-specific antibodies (DSA) and negative T cell cytotoxic crossmatches were compared with 88 ABO-incompatible (ABO-I) and 207 ABO-identical/compatible (ABO-Id/C) RTx. The desensitization therapy consisted of mycophenolate mofetil, rituximab and double-filtration plasmapheresis. Protocol biopsies within 1 year revealed subclinical CAMR in 36% of HLA-I, 5% of ABO-I and 3% of ABO-Id/C, although clinical acute AMR was observed in 8%, 3% and 1%, respectively. The incidence of CAMR was not different between class I and class II DSA. Most of class I DSA (94%) changed to negative 1 year after RTx, whereas 77% of class II DSA remained positive. In addition, the remaining DRB ± DQB DSA caused CAMR in 80% of patients, while DQB DSA alone did not. The progress of subclinical CAMR within 1 year could not be circumvented by rituximab. Sustained class II (DRB ± DQB) DSA detection after RTx may pose a potential risk for developing CAMR, but negative change in class I DSA could also elicit CAMR.

Yamanaga S ，Watarai Y ，Yamamoto T ，Tsujita M ，Hiramitsu T ，Nanmoku K ，Goto N ，Takeda A ，Morozumi K ，Katayama A ，Saji H ，Uchida K ，Kobayashi T ... -  《-》

[ABO incompatible living donor kidney transplantation: a dream come true. Experience of Hospital Clínic of Barcelona].

Oppenheimer F ，Revuelta I ，Serra N ，Lozano M ，Gutiérrez-Dalmau A ，Esforzado N ，Cofán F ，Ricart MJ ，Torregrosa JV ，Crespo M ，Paredes D ，Martorell J ，Alcáraz A ，Campistol JM ... -  《NEFROLOGIA》

Isoagglutinin adsorption in ABO-incompatible transplantation.

As the demand for kidney transplantation is constantly growing methods to expand the donor pool have become increasingly important. ABO-incompatibility has hitherto been regarded as an absolute contraindication to living donor donation. However, as ABO-incompatibility has accounted for the majority of living donor exclusions, efforts have been made to overcome this immunologic barrier. Successful desensitization protocols thus far, have combined plasmapheresis for antibody removal with splenectomy to reduce the antibody producing B-cell pool, in addition to quadruple immunosuppression. Although good graft function has been achieved, the high risks involved have been deterrent. We have developed a protocol for ABO-incompatible kidney transplantation based on antigen-specific immunoadsorption and rituximab, in combination with standard maintenance immunosuppression (tacrolimus, mycophenolate mofetil and corticosteroids). We hypothesized that the anti-A/B antibodies could be effectively eliminated and good graft function achieved, without the complications of coagulopathy and transfusion reactions associated with plasmapheresis. Furthermore, we hypothesized that the substitution of splenectomy with a single dose of the anti-CD20 antibody rituximab would further reduce surgical risk as well as the risk of infectious complications. In 2001 the program for ABO-incompatible kidney transplantation was started at our center. To date 50 ABO-incompatible kidney transplantations have been performed according to the protocol based on antigen-specific immunoadsorption and rituximab. Safety and efficacy of the protocol has been evaluated in several studies, all showing that the antigen-specific immunoadsorption is well tolerated and without any serious side effects. Patient and graft survival as well as kidney function have been comparable to that of ABO-compatible living donor kidney transplantation and the incidence of antibody-mediated rejection 0%. We conclude that AB0-incompatible kidney transplantation using a protocol based on antigen-specific immunoadsorption and rituximab, in combination with triple immunosuppressive therapy is safe and effective. ABO-incompatibility following this protocol does not have a negative impact on graft function. ABO-incompatible kidney transplantation is equivalent to standard ABO-compatible living donor kidney transplantation.

Genberg H ，Kumlien G ，Wennberg L ，Tydén G ... -  《TRANSFUSION AND APHERESIS SCIENCE》