1. OPTN Kidney Paired Donation (KPD) Histocompatibility Testing Policies
Kidney Transplantation Committee
Richard Formica, MD (Chair)

2. Dedication to Elizabeth.

3. Strategic Plan #6- Promote Efficient Management of the OPTN
Decrease the number of match failures due to HLA antibody and crossmatching issues
#1- Increase the number of transplants
Prevent ‘breaking chains’ so that compatible pairs can proceed to transplant
This proposal actually meets several of the goals in the OPTN strategic plan, including improving patient safety, increasing access to transplants, and increasing the number of transplants. But, just like the Histo Committee’s proposal, the proposed changes will greatly increase efficiency in the management of the OPTN and its KPD program. So, we are going to focus today on the efficiencies that we can gain from these changes.

4. The Problem Relatively low match success rate in OPTN KPD program
Antibody related issues and positive crossmatches continue to account for a significant number of match failures
Insufficient histocompatibility testing requirements to prevent match failure
While the OPTN KPD program has made great strides, the match success rate in the program still remains low. Matches can fail for a variety of reasons, but we know that a number of our matches fail due to antibody related issues and unexpected positive crossmatches.
And, obviously, the consequences are great when a chain breaks and the donors and candidates end up missing out on a subsequent match run and additional transplant opportunities.
This proposal seeks to put in place histo testing policies that will help prevent some future match failures.
If asked for specific data on these points:
Data provided to the KPD Workgroup show that 52% of failed matches were not actually refused, but did not proceed to transplant due to refusals of other matches in the same exchange. Of the matches through mid-April 2013 that were refused, 30% were refused due to either “positive crossmatch” or “unacceptable antigens.”
An analysis of data through September 30, 2013 showed that crossmatch or antibody-related issues continue to account for approximately 30% of refusal reasons. Of the crossmatch-related refusals, about 1/3 were due to an actual positive crossmatch, while 2/3 were due to unacceptable antigens.

5. Proposed: HLA Typing
Full list of HLA types must be reported on KPD donors
List of HLA types required for all candidates consistent with those for DD kidney policy
If candidate has unacceptable antigens, the corresponding HLA type must be reported
Molecular HLA typing required for candidates
Candidate’s hospital must retype donor to confirm HLA type
New HLA typing requirements:
Under the proposal, a full list of HLA loci is required for donors. The list is consistent with what the Histo Committee just presented for deceased donors. DQA and DPB are new types.
A requirement for donors and candidates to be typed using molecular methods. This was a recommendation from our Histo Advisory Committee since molecular typing is a much superior method in determining compatibility. It was also one of the findings from the KPD Consensus Conference. Molecular typing is currently required on all deceased kidney donors as well. It is not currently required for candidates on the waiting list for a deceased donor kidney.
{When Ken Andreoni asks, molecular typing is being required on candidates in order to better interpret antibodies (to self or not}.
Many of the public comments also suggested that candidates with antibodies to certain types need to have additional HLA information reported. So, we included this in the proposal.
Finally, the candidate’s hospital is required to retype the donor to confirm the donor’s HLA type before transplant.

6. Proposed: Antibody Screenings
Candidate’s transplant hospital must screen all KPD candidates for antibodies:
every 90 days (+/- 20 days)
when potentially sensitizing event occurs
if candidate reactivated after more than 90 inactive days
if unacceptable positive crossmatch occurs that prevents transplant with matched donor
Physician/surgeon (or designee) and lab director (or designee) must review UAs listed for candidate before their first match run.
There are new antibody screening requirements as well. Our Histo Advisory group recommended that hospitals screen candidates for antibodies every 90 days, when a potentially sensitizing event occurs, if the candidate is reactivated after having been inactive for more than 90 days, and in case where a candidate and donor have been matched and there is an unacceptable positive crossmatch that prevents a transplant (and therefore contributes to match failure). Several of these screening time periods are recommended by the findings in the KPD Consensus Conference.
When performing antibody screenings, labs would be required to use a method that is at least as sensitive as their crossmatching method (a recommendation from ASHI).
And, the candidate’s physician or surgeon (or designee) and the histocompatibility laboratory director (or designee) must review and confirm the unacceptable antigens listed for the candidate before their first match run. This again goes toward preventing refusals later in the match process because of unacceptable antigens. It is also based on a recommendation in the KPD consensus conference findings that physicians and histo lab personnel should have regular communication on candidates in a KPD exchange. This is also consistent with a requirement in the new KAS pertaining to patients with CPRA at or above 98%.

7. Proposed: Crossmatching
Candidate’s transplant hospital must:
perform physical crossmatch before donor’s nephrectomy is scheduled and final crossmatch prior to transplant
report crossmatch results to donor’s transplant hospital and UNOS
report a reason for unacceptable positive crossmatch within 7 days
If unacceptable positive crossmatch occurs that breaks the chain, UNOS will make candidate ineligible before next match run. Candidate will be eligible once candidate’s program reports that a review of UAs is complete.
Finally, the proposal contains new crossmatching requirements.
The original public comment proposal required the candidate’s hospital to perform a preliminary crossmatch before the matched donor’s recovery procedure. Several public comments pointed out that the crossmatch would need to be performed earlier in order to avoid match failure later in the process. In addition, federal regulations require histocompatibility laboratories to perform a final crossmatch and have the results available before a kidney transplant.
The proposal specifies that the candidate’s transplant hospital is responsible for performing a physical crossmatch before the donor’s nephrectomy is scheduled. The candidate’s hospital must report the results to the OPTN Contractor and the matched donor’s transplant hospital.
In addition, the proposal would require that a candidate’s hospital inactivate a candidate prior to before the next match run if an unacceptable positive crossmatch occurs between a matched pair that prevents transplant. The physician/surgeon and histo lab director must review the unacceptable antigens listed and the hospital must report the reason for the positive crossmatch to UNOS within 7 days.

8. Overview of public comments
Type of Response
Response Total
In Favor
In Favor as Amended
Opposed
No Vote/
No Comment/ Did Not Consider
Individual 45 43 2
Regional 11
Committee 1 20
Professional Societies 5
The public comments on this proposal were overwhelmingly favorable among the regions, individuals and other committees.
Five professional societies commented on the proposal. All five supported the proposal. The American Society for Histocompatibility and Immunogenetics (ASHI) and the College of American Pathologists (CAP) requested some tweaks and clarifications to the proposal and those have been made.

9. What Members Will Need to Do
Perform molecular typing on donors
Report all required donor HLA info
Arrange shipment of donor blood sample to candidate’s hospital or histocompatibility laboratory
OPTN KPD Donor Hospital
Perform/report molecular typing on candidates for all required HLA types
Confirm donor HLA
Perform/report/confirm antibody screenings at all required time periods
Perform crossmatch at specified time periods and report results to UNOS and donor hospital
OPTN KPD Candidate Hospital
These new policies would only be applicable to programs participating in the OPTN KPD program. They do not apply to other KPD programs.
The KPD donor hospital will be responsible for all donor typing and for arranging shipment of the donor blood sample to the candidate’s hospital or lab for the crossmatch.
The KPD candidate hospital will be responsible for:
all candidate typing and confirming the donor’s HLA type.
Performing and reporting antibody screenings at the required frequency
Performing crossmatches at the specified time periods and communicating the results to UNOS and the donor hospital.

10. Overall Project Impact
Product
Policy
Target Population Impact:
OPTN kidney paired donation (KPD) candidates
Total IT Implementation Hours
Total Overall Implementation Hours
1,650/10,680
Overall project impact:
This involves policy changes that will affect KPD candidates.
The IT implementation impact is in the very large category.
2290/17,885

11. Cost v. Benefit Cost Total implementation hours =2,990 ($180k)
IT hours = 1,650
Very Large category
Benefit
Increase efficiency in OPTN KPD
Increase # of living donor kidney transplants
Increase access for candidates waiting for a DD kidney
Improve safety for KPD candidates
Increase competitive edge with other KPD programs
I acknowledge that this proposal is in the ‘very large’ category in terms of what it will cost for UNOS to program and implement.
However, there is tremendous benefit to kidney candidates and the OPTN with these changes.
These changes will lead to more transplants in the KPD program, which means more access for candidates waiting for a deceased donor kidney.
They will improve safety for candidates in the program and increase the overall efficiency.
Possible question: What do other KPD programs do and how will we compare with these new changes?
A: Many of the large players in KPD have robust programming to prevent match failures related to antibody and crossmatching issues. It’s also worth noting that some programs actually fine transplant programs when their candidate has an unacceptable positive crossmatch that breaks a chain. These changes allow us to have a more nimble system and be more competitive with other programs.

12. Resolution 21 (page 79)
RESOLVED, that additions and modifications to Policies 13: (Kidney Paired Donation (KPD)); 13.5 (Histocompatibility Testing); 13.6 (Matching within the OPTN KPD Program); 13.7 (KPD Screening Criteria); and (Crossmatching Protocol), as set forth on page 79, are hereby approved, effective pending programming and notice to the OPTN membership.
Please review Resolution 21, found on page 79 of your Board book and the related amendment handout in front of you.

13. Extras

14. Background 2012 KPD public comment proposal
2012 KPD Consensus Conference hosted by societies
2014 public comment proposal incorporates feedback all of the above and the OPTN/UNOS Histo Committee
This proposal has been around for awhile.
In March 2012, the Committee distributed a proposal converting sections of the KPD Operational Guidelines into policy.
Among them were proposed policies governing histocompatibility testing.
The majority of the 2012 proposal received support, but there were a number of comments pertaining to the histocompatibility policy sections missing critical elements. The Committee opted to reserve the histo section and formed a Histocompatibility Advisory Committee (HAC) to recommend how the policy proposal should be amended.
Around the same time, a number of professional transplant societies convened a KPD consensus conference. The recommendations in this proposal reflect those that came out of the Histo Advisory Committee and incorporate feedback received during the spring 2012 public comment period, the 2012 KPD consensus conference findings, and the OPTN/UNOS Histocompatibility Committee.