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ABO incompatible Kidney transplantation.

early data coming from Japan demonstrated successful long-term survival ABOi KTx, in addition to subsequently coming successful results of the ABOi Ds

ABO incompatibility (ABOi) Kidney transplantation.

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List of abbreviations:

o   ABOi: ABO blood group-incompatible,

o   HLAi: incompatible HLA,

o   DDA: deceased-donor allograft.

o   AB: antibodies.

o   Rtx: rituximab.

o   KTx: Kidney transplantation,

o   IVIG: intravenous immune globulins,  

o   Tx: transplantation

o   Tac: tacrolimus

o   TR: Transplant recipients,

o   MMF: Mycophenolate Mofetil,

o   HLA: human leukocyte antigen,

o   im/m: Immunosuppressive,

o   rATG: rabbit antithymocyte globulin,

o   CI:  contraindications.

o   KTx: kidney transplantation.

o   Dsz: Desensitization.

o   Ag(s): Antigen(s).

o   AB(s): Antibodies.

o   DDA: deceased-donor allograft.

o   PE: Plasmapheresis.

Tissue & blood incompatibility have commonly been considered an absolute CI to tx. This was primarily attributed to the historical poor outcome if tx was proceeded against tissue or ABO blood type barrier. However, early data coming from Japan demonstrated successful long-term survival ABOi KTx, in addition to subsequently coming successful results of the ABOi Dsz protocols in the US and elsewhere that triggered more interest in this maneuver.

The ABO blood grouping composed of 4 commonly seen categories (A, B, AB, & O), with types A & O most frequently observed in the US population. Ag is expressed on RBCs, lymphocytes, & platelets, in addition to epithelial & endothelial cells. Formation of blood group AB(s) developed against the Ag(s) that are not native to the host. So, AB(s) to both A & B can be seen in an individual with blood type O, while an individual with blood type AB has no AB(s) to A or B Ag(s). Considering the distribution of blood group Ag(s) in the US, waiting timing on the DDA list is extremely prolonged for ptns with blood group B or O.  The main target of ABO Dsz is to limit the immunogenicity of the incompatibility process to permit successful tx with commonly administrated induction & maintenance im/m protocols. Despite the lack of uniformly accepted ABO im/m regimen, the most commonly administrated protocols may include a combination of the following:

o   Extracorporeal removing the circulating ABO ABs, via e.g., PE or immunoadsorption  

o   Immunomodulating the recipient immune system, typically via IVIG  

o   Depleting B cell population responsible for ABO AB production, most commonly via the anti-CD20 agent Rtx.

ABOi tx TR must satisfy centre-specific, general tx selection criteria in addition to ABOi-related criteria. There’re no general concordance regarding ABOi-related selection criteria for TR. The following criteria have been suggested:

o   Ptn must show an initial ABO isoagglutinin titre of 1:128. In certain centres, an initial titre of 1:256 can be acceptable.

o   Ptn must be willing to perform ABOi tx with all therapies related to ABOi tx.

o   Concurrent HLA Dsz is NOT allowed. However, this practice is variable from centre to another, & simultaneous HLAi & ABOi tx can be performed in certain centres.

o   Prior authorization regarding insurance for all therapies related to ABOi tx.

Ptns undergoing ABOi tx, we start a Dsz protocol beginning one mo before the scheduled tx surgery and involving the combination of Rtx, PE, & IVIG to deplete B cells and limit the circulating anti-AB levels. Tx is proceeded when the isoagglutinin AB titre reaches 1:8. Optimized induction therapy in ptns receiving a KTx from an ABOi donor is not well known. However, the use rATG-Thymoglobulin as induction im/m regimen in these ptns is currently suggested.

 

In TR of an ABOi kidney tx, we provide the triple therapy maintenance im/m protocol including a CNI (Tac) + an antimetabolite (MMF) + prednisone. This combination is simulating the initial maintenance im/m used in most ABO-compatible kidney TR, with the exception of MMF (started 4 weeks before tx instead of the day of tx surgery). In ABOi TR, targeting a higher whole-blood Tac levels compared to ABO-compatible TR:

o   8 -12 ng/mL for the 1st month after Tx

o   5-10 ng/mL for subsequent months

Following ABO Dsz and tx, ptns should be monitored with the same approach that used in TR of ABO-compatible tx. Moreover, isoagglutinin titre daily monitoring while ptn still in the hospital, 2-3 times/wk for the 1st mo post-tx, weekly for months 2-3 post-tx, and then yearly thereafter. Ptns with a post-tx isoagglutinin titre ≥1:16, a graft biopsy and/or pre-emptive PE should be commenced, especially with evidence of allograft dysfunction (e.g., delayed/slow graft function or increasing SCr). We do not advise routine protocol PE post-tx, irrespective to the isoagglutinin titre. We advise protocol biopsies (unless CI) in all ABOi TR at 14 ds and again at one y post-tx.  

Complications of ABOi Tx may include higher rates of peri-operative bleeding and lymphocele with higher risks of infectious episodes. ABOi TR do not show higher risk of malignancy as compared to ABO-compatible TR.