Collaboration for incompatible couples. Hypersensitive and ABO incompatible couples

Collaboration for incompatible couples. Hypersensitive and ABO incompatible couples. 

Introduction

ABO blood group incompatibility or pre-existing donor human leukocyte antigen(HLA)  antibodies(DSA) are major barriers to living donor kidney transplantation. More than 50% of recipients are losing their chances for living donor transplantation because of inappropriate pairs. We have three programs for living donor kidney transplantation for these incompatible couples:

1. High Sensitization Transplantation Program,
2. ABO Incompatible Transplantation Program
3. Paired Donation Program

The main principle is to have extended long term graft and patient survival for our incompatible couples. The kidney recipients are initially evaluated for HLA DSA and the ABO blood groups. We perform desensitization protocol if the blood groups are matching with the donor and the long term outcome of the kidney graft will not be hazardous because of high immunologic risk. If the blood groups are not matching, we perform ABO incompatible transplantation for couples who can have a match in short period of time. If the recipient and donor are not compatible for long term successful kidney transplantation, matching these incompatible couples and sharing kidneys pairing these couples enable safe and successful kidney transplantation. We perform 17% of our living donor transplantation by paired donation program. Paired donation not only offers a new chance for transplantation of inappropriate couples, it also provides better outcome with lower rate of complication and cost. As the number of couples applied for paired donation list increases, the chances for finding better match improve as well. The increased number of living donor kidney transplantation at our program enables finding better matches with a computer program.

Figure 1: Algorithm for ABO Incompatible Couples and Highly Sensitized Patients

 

High Sensitization Transplantation Program

Blood transfusion, previous organ transplantation and previous pregnancies (with or without live birth) causes the immune system to meet human tissue. If the immune system recognizes and starts to make antibodies against HLA, we need to measure the titer and the specific HLA tissues with immunologic recognition. High sensitization of the recipient is the most important initial screen for pre-transplant evaluation of recipient. Our Tissue Typing Lab perform Single Bead HLA Screen assay to evaluate these antigens with the most sensitive and specific results. We also perform high resolution HLA Screen for the donors that reveal four digit results offering subgroup differentiation of specific HLA Tissue. We use desensitization protocol for cases that have acceptable immunologic risk for long term kidney survival. The recipients with positive T cell Flow Crossmatch and B cell CDC Crossmatch are eliminated from desensitization. The main principle for the patients for acceptable immunologic risk is to evaluate the possibilities to find a quick match from the paired donation list. The ones who do not have chance to find a match for more than a year are evaluated selectively by informing the recipient and the donor for the possibilities in time. These are the high risks that may cause

• One HLA antibody against donor with an MFI more than 10000 units
• Two or Three HLA antibodies against donor with an added MFI of more 10000 units
• More than three HLA antibodies against donor with MFI more than 2000 units

Our previous studies revealed that our long term results with acceptable immunologic risk is comparable to control group. The recipients with a lower estimated long term kidney survival are referred to paired donation program.

ABO Incompatible Transplantation Program

Recipients with Blood Group O are the main group that can benefit from ABO incompatible transplantation. Because these recipients can hardly find a matching couple at paired donation list and may need to wait for years even if they have a living donor. We check Anti A/B Isohemagglutinin levels for these patients and if the titers are less than 1/32 we especially refer these couples for ABO incompatible transplantation. ABO incompatible transplantation requires pretransplant treatment with specific vaccination. And also we administer rituximab treatment and perform immunadsorbtion methods (mainly double filtration) to decrease the isohemagglutinin antibodies to titers of 1/8-1/4 before transplantation. We have successful results at ABO incompatible transplantation for recipients with low Anti A/B titers. So recipients with Isohemagglutinin titers less than 1/64 are referred to ABO incompatible transplantation if they don’t have chance to find a quick match at paired donation program.

 

Paired Donation Kidney Program

 

Paired Donation Kidney Program is the most important aspect to find compatible matches for living donation. Brotherhood/Sisterhood for offering a gift of life is not only a great solution but also a priceless gift shared with other people. We believe it’s always an impressive feeling to give a gift of life to your loved one but paired donation offers touching to another person’s life as well.

Any recipient with a living donor related to recipient according to legal kinship can participate to our list. According to the Regulation of Organ and Tissue Transplantation Service in Turkey, living-donor organ transplantation can be performed from the recipient’s spouse, lived together at least for two years, and relatives until the fourth degree (including the fourth degree). The recipients may participate to paired donation program with more than one living donors which may increase their chance for better match. We initially require the basic information including

age, gender, marital status, previous pregnancies, health history and systemic evaluation of the recipient and donor. The mandatory lab work will be the HLA typing of donor and recipient, as well as human leukocyte antigen Antibodies (DSA) of the recipient. The local physician can check the basic blood chemistry to rule out prominent disease. We recommend detailed evaluation by the local nephrologist after finding definite match for paired donation.

The procedure to match two or three couples

Simultaneous surgery during paired donation is performed at Florence Nightingale Paired Donation Program. Initially the donor surgery starts at similar time and kidney exchange occurs while transplanting kidneys to the recipients at the same time. We perform dual or triplet pairing according to the results of computer program. Our computer program for matching depends on age, HLA mismatch, gender and Kidney functions (Glomerular Filtration Rate). Our matching program matches high resolution Donor Specific Antibody results of recipients with compatible donors in regards to titers. Therefore immunologic risk evaluation is the major benefit for high sensitized patients enrolled into the paired donation list. The best matches are listed and the evaluation for paired donation starts after assuring agreement from matching couples.

Evaluation for pre-transplant evaluation at our center

After finding a match for a foreign recipient, it is preferentially better to perform the initial tests by the local physician. It is vital to be prompt for local evaluation because the other matching couple can have time limitations most of the time. The donor and recipient will be invited to our center at the first convenience. The pretransplant evaluation with examination and screen of donor and recipient including tissue typing tests will be completed. It must be mentioned that it is not infrequent to cancel the transplantation because of donor evaluation revealing ineligible for living kidney donation or differences in immunologic studies resulting increased immunologic risk. If the couples are eligible for matching, simultaneous kidney paired exchange will be performed.

The procedure of Kidney Transplantation

The couples are introduced during a meeting the day before the surgery. It is important to explain all details about exchanging kidneys including the qualifications of exchanged kidneys and get a formal consent during this meeting. We perform simultaneous transplantation of two or triple couples at the same time. As a rule, both transplants are intertwined accordingly and donor surgeries are engaged initially. We perform Hand Assisted or Robotic Assisted Retroperitoneoscopic nephrectomy for the donors. These techniques are safer as they avoid intraabdominal complications. Generally the hospital stay for donor is three days and for recipient it’s five to six days. Our kidney transplantation package enables coverage for extended stay up to 9 days therefore there is enough coverage for couples involved from other countries.

The important limitations of Paired Donation

 

The matching issue can be more challenging if the ABO incompatible recipient has also preexisting HLA Antibodies (DSA). Because at that situation it is mandatory not only to find matching blood group but also a donor match with HLA Tissues that does not come across with recipient’s DSA is required. Blood group A recipient and B Donor (A – B) and the reciprocal B – A are couples that can find match in short period of time. If the recipient has hypersensitization (DSA) the period to find a match can take longer. The highly sensitized patient with blood Group AB can also find a match especially if the donor is blood group O. AB recipients with donors from non AB Groups ( AB – A, AB – B) can find a match also in months. But a high sensitized AB – AB couple is a very challenging group to match because they can only match with another AB – AB couple. The situation is similar for highly sensitized recipient with Blood Group O who have a donor who is O as well(O – O).

Table 1: The recommendations to couples in regards to their Blood Groups and HLA sensitization.

Blood group of recipient	Blood group of Living donor	Initial recommendation	Estimated Waiting time at paired donation list
A	B	Paired Donation	Immediate to Months
B	A	Paired Donation	Immediate to Months
O	Non O	ABO Incompatible TX	Months to Years
A*	A	Paired Donation	Months to Years
B*	B	Paired Donation	Months to Years
AB*	Non AB	Paired Donation	Months to Years
AB*	AB	Paired Donation	Very difficult
O*	O	Paired donation	Very Difficult

* High PRA Patients (If they have high and many HLA Antibodies, it can be harder to find a suitable match)

The most important limitation is imbalance between O donor and non-O recipients in the ABO blood group type distribution in general population and incompatible donor recipient pairs (O – A, O – B). O – AB can be more challenging to find a match. We initially check the A and B Isohemagglutinin titers of recipients and recommend ABO incompatible transplantation if the titers are less than 1/64. We do not recommend ABO incompatible transplantation for recipients with titers 1/128 and higher unless there are specific circumstances. For couples not appropriate for ABO incompatible transplantation, paired donation list can offer some benefits. We perform imbalanced match for these cases who have less chance to match with other groups. This means we offer a better kidney (younger, better HLA Match, better GFR) to a compatible couple to persuade enrolment to paired donation program. Best examples are A – O and B – O couples are most frequent couples persuaded to enroll paired donation so that couples O – A and O – B can pair. The imbalanced match is a good source to offer safe transplantation to O group recipients with non O donors.