ABO blood group matching between the kidney donor and the recipient was considered to be absolutely essential for a successful outcome of a kidney transplantation. A donor with blood group O was considered as a universal donor and AB group considered a universal recipient. A recipient with blood group A could receive a kidney from a donor with blood groups, either A or O ; likewise , a recipient with blood group B could receive a kidney with blood group B or O. Thus, ABO incompatibilty had long been considered a contraindication to kidney transplantation. This lead to a situation wherein many relatives who were willing to donate a kidney to their near ones were not accepted as kidney donors. This perception remained till the first reports of successful ABO incompatible transplantations were published from Belgium in 1982. Such transplants are now being done in Japan, US and Europe.
Blood Group Antigens & Antibodies
ABO antigen system is composed of oligosacharide expressed on erythrocytes(Red blood cells). These antigens are also expressed in endothelial cells, glomeruli and tubules. Antibodies to A and B antigens are formed during early infancy. These antibodies are predominantly of IgM class; but can also be of IgG and IgA class, especially in blood group O individuals.
The immune system forms these antibodies against whichever ABO blood group antigens are not expressed on the individual’s RBCs. Thus, group A individual has anti B antibodies and vice versa; both anti A and anti B antibodies are found in individuals with blood group O; people with AB group do not have any antibodies. Successful ABO incompatible kidney transplantation requires removal of these antibodies against the donor blood group antigen; this process is called desensitization.
Desensitization for ABO incompatible Transplant
Recipients are subjected to desensitization procedures prior to transplant to lower anti A / anti B antibody levels to acceptable limits.
These strategies include
Removal of antibodies using Plasmapheresis or immunoadsorption
Reducing further production of AB antibodies using Rituximab
Immunomodulation using intravenous immunoglobulin (IV Ig)
Desensitization protocols do vary a bit across various transplant centres; almost all the centres use a combination of above methods to achieve target anti A / anti B levels. Acceptable antibody levels prior to transplantation vary from 1:8 to 1:16
Maintenance immunosupression in these patients consists of the triple drug regimen that include Tacrolimus, Mycophenolate mofetil and Prednisolone.
Patient & graft outcome
In the past, patient and graft survival following ABO incompatible transplantation was reduced by high rates of sepsis related mortality and antibody mediated rejections. Recent data reveal excellent patient and graft survival in these patients; the results comparable to ABO compatible transplant are achieved in some centres ; current data shows 5 year survival rates of more than 90%. Initial studies reported are incidence of antibody mediated rejections to be 20-30%. However with Rituximab based regimens, the rejections have reduced significantly, to as low as 5%.
Compared with ABO compatible transplantation, these recipients are at a higher risk of infections including pneumonia, urinary infections and wound infections. These patients are also at higher risk of viral infections caused by cytomegalovirus, B.K virus. Higher rates of perioperative bleeding is seen in ABO incompatible transplant recipients, likely due to depletion of clotting factors by plasmapheresis. This can be avoided by carefully correcting coagulopathy prior to transplant by fresh frozen plasma infusion. A higher rate of lymphoceles has been reported, the reasons for which are currently unclear. Significantly, despite more intensive immunosupression, there has been no difference in risk of malignancies compared to ABO compatible transplant recipients.
ABO incompatible transplantation has come a long way since its early days. The patient and graft survival are now comparable to ABO compatible transplantation. These encouraging results would help several patients who lack a blood group compatible donor to realise their dream of a successful kidney transplantation. The Renal transplant Unit at Aster Medcity, Kochi does ABO incompatible transplants with excellent results.
