Donation and Transplantation Kidney Paired Donation Program Data Report

Donation and Transplantation Kidney Paired Donation Program Data Report 2009-2013

Extracts of the information in this report may be reviewed, reproduced or translated for educational purposes, research or private study but not for sale or for use in conjunction with commercial purposes. Any use of the information should be accompanied by an acknowledgement of Canadian Blood Services as the source. Any other use of this publication is strictly prohibited without prior permission from Canadian Blood Services. Canadian Blood Services assumes no responsibility or liability for any consequences, losses or injuries, foreseen or unforeseen, whatsoever or howsoever occurring, which might result from the implementation, use or misuse of any information or recommendations in this report. This report contains recommendations that must be assessed in the context of a full review of applicable medical, legal and ethical requirements in any individual case. Production of this report has been made possible through a financial contribution from Health Canada, and the Provincial and Territorial governments. The views expressed herein do not necessarily represent the views of the Federal, Provincial or Territorial governments. Canadian Blood Services 1800 Alta Vista Drive Ottawa, Ontario K1G 4J5 Canada 613-739-2300 Email: info@blood.ca On the cover: In May 2011, three-year-old Kate received the life-saving kidney she so desperately needed as part of a domino kidney exchange facilitated by the Canadian Kidney Paired Donation Program. Her father, Will, donated to someone else in the chain to help make this possible. 1

Executive Summary Canadian Blood Services is pleased to release the Kidney Paired Donation Program Data Report which summarizes data for the Kidney Paired Donation (KPD) Program for the years 2009 2013. The publication of this information marks the first of a series of data reports that will be produced annually and eventually expanded to include data on all the interprovincial organ listing and sharing programs. These data were selected to describe the activity of the Canadian Organ Donation and Transplantation Network (CODTN) in service to transplant candidates and donors participating in the KPD Program. It also may be used to identify current barriers and other issues that require resolution so that opportunities are maximized for low immunological risk transplants and greater equity may be realized for those within the Canadian living donation and transplantation landscape. Original modelling predicted that the Canadian population could expect 109 paired exchange transplants (exchanges between only 2 pairs) from the enrollment of 280 new pairs per year. After the running of the first Match Cycle in January 2009, it was clear that the ability to identify closed chains of 3 or more pairs and domino chains beginning with non-directed anonymous donors could greatly increase transplant opportunities. Modification to the matching algorithm to handle these expanded chains yielded immediate results and in 2013 the KPD Program activity reached a high of 85 transplants. This is 78% of the original prediction of 109 paired exchange transplants and was achieved with only 128 new pairs, 46% of the predicted 280 needed. The 85 living kidney transplants translate to a rate of 2.4 per million population. Over the past 5 years, the KPD Program has seen a gradual increase in enrollment of new registered pairs, non-directed anonymous donations and transplants performed. However, to maximize transplant opportunities within the KPD Program, it is imperative to explore strategies that will support increased registration rates and overall pair participation. In addition, the data show that for the time period 2009-2013, the median time to chain completion is 111 days from the time that patients are informed of a match. As chains are less likely to be delayed or to collapse if surgeries can be scheduled quickly after match proposals, the exploration of system efficiencies to improve the time to transplantation will also contribute towards maximizing transplant opportunities from the program. This report is just one of the building blocks in the evolution of the national transplant data system which will offer an improved understanding of the long term outcomes of those patients who have received a transplant through the KPD Program. The data provided in this report documents the excellent short-term outcomes and low rejection rates associated with transplantation through the KPD Program. This program has also played an important role in providing patients access to a superior transplant option. Previously, transplant candidates with an incompatible living donor would not have had the opportunity to receive a living donor transplant at all, would have been added to an ever growing deceased donor waitlist, or would have had to proceed with an incompatible living donor transplant under immunologically suboptimal circumstances. 2

Canadian Blood Services acknowledges, with gratitude, the commitment of the Kidney Transplant Advisory Committee (formerly the National Kidney Registries Advisory Committee), the Living Donation Advisory Committee, the National HLA Advisory Committee, the Organ Donation and Transplantation Executive Advisory Committee, and those whose advice supports the continued growth and achievements of the KPD Program. The KPD Program remains indebted to the administrators, physicians, surgeons, transplant coordinators and allied health professionals of the Living Donation and Transplant Programs for their efforts and collaboration. Their commitment to success and excellence has driven these accomplishments for transplant recipients in Canada. 3

Table of Contents EXECUTIVE SUMMARY... 2 1.0 INTRODUCTION... 6 1.1 Report Scope... 6 1.2 Data Sources... 6 2.0 HOW THE KPD PROGRAM WORKS... 7 3.0 KPD PROGRAM SUMMARY... 8 4.0 KPD CANDIDATES AND DONORS... 9 4.1 Age... 9 4.2 Sex... 9 4.3 Blood Group... 9 4.4 HLA Antibody Levels... 10 5.0 MATCH CYCLE STATISTICS... 10 5.1 Chain Length and Time to Completion... 10 5.2 Match Declines... 11 Table 4: Reasons for Match Declines 2009-2013... 11 5.3 Travel... 12 6.0 OUTCOMES... 12 6.1 Program Performance... 12 6.2 Recipient Outcomes... 12 7.0 CONCLUSION... 13 APPENDIX 1: GLOSSARY... 14 APPENDIX 2: MATCHING ALGORITHM... 18 APPENDIX 3: ADDITIONAL DATA FOR KPD PROGRAM SUMMARY 2009 TO 2013... 20 APPENDIX 4 ADDITIONAL DATA FOR KPD CANDIDATES AND DONORS... 24 Section 4.1 Age... 24 Section 4.2 Sex... 25 Section 4.3 Blood Group... 26 Section 4.4 HLA Antibody Levels... 28 APPENDIX 5 ADDITIONAL DATA FOR MATCH CYCLE STATISTICS... 31 Section 5.1 Chain Completion... 31 Section 5.2- Donor Disposition... 33 Section 5.3 Travel... 35 APPENDIX 6 ADDITIONAL DATA FOR KPD PROGRAM OUTCOMES... 36 4

Section 6.1 Participant Withdrawal... 36 Section 6.2 Recipient Outcomes... 36 5

1.1 Report Scope 1.0 Introduction The framework for a Canadian kidney paired exchange program evolved from the reports arising from a number of donation and transplantation stakeholder forums and consultations under the Canadian Council for Donation and Transplantation. In 2008, the Conference of Deputy Ministers approved the plan for Canadian Blood Services to begin the operational development of the Living Donor Paired Exchange (LDPE) Program, and to test it as a pilot program in collaboration with three provinces British Columbia, Ontario and Northern Alberta. By November 2010, all provinces were fully participating. In December 2014, the LDPE Program was renamed and is now referred to as the Kidney Paired Donation (KPD) Program. The goal of the KPD program is to identify and facilitate kidney transplant opportunities for end stage renal disease (ESRD) patients who have a willing but incompatible living donor. The first KPD transplants were performed in June 2009. By the end of 2013, this program had resulted in the completion of 271 transplants. As part of its mandate, Canadian Blood Services is responsible for reporting on the activities of the inter-provincial organ listing and sharing programs that it manages and operates for the Donation and Transplant programs and governments. This report contains data and information from the KPD Program for the first five years of its operation. The information contained in this report covers the five year period from January 1, 2009 to December 31, 2013. The first sections (2.0 and 3.0) provide an overview of how the KPD Program works, and a brief summary of program activity. Section 4.0 provides greater detail regarding candidate, transplant recipient and donor characteristics. Section 5.0 provides information on why potential transplant opportunities are declined and how long it takes to complete a chain of donor exchanges. Section 6.0 covers program performance and transplant outcomes for KPD Program participants. A Glossary of terms is provided in Appendix 1 and additional detail including graphs and data are presented in Appendices 2 6. 1.2 Data Sources Data for KPD Program activities has been extracted from the Canadian Transplant Registry. This is the information technology (IT) system developed and maintained by Canadian Blood Services in which patient data is stored and the matching algorithm is run. Additional data has also been provided directly by the provincial Living Donation and Transplant Programs. Unless otherwise stated, data presented is for the five year period of 2009-2013. 6

2.0 How the KPD Program Works The KPD Program is dependent upon the generosity and altruism of donors, and there are 3 types of donors that can enroll. The most common donor is an incompatible donor; one who wishes to donate directly to someone they know who needs a kidney transplant (a transplant candidate) but for whom testing has shown that there is a high chance that the donor s kidney will be rejected if it is transplanted to that candidate. In this situation, they have the opportunity to register together with the national KPD Program to search for a potentially compatible kidney donor for the candidate. A second type of donor is a Non-Directed Anonymous Donor (NDAD). This is a person who contacts their local Living Donation Program offering to donate a kidney to anyone in need. After an exhaustive process of evaluating the donor and his/her kidney for safe donation, the person is offered the opportunity to enroll in the KPD Program to potentially help a number of candidates find a transplant through a domino exchange. The third type of donor is one who is medically compatible with the person they know and to whom they would like to donate, but for reasons agreed to by the pair and their transplant team, they wish to enroll in the program. For example, the donor s kidney anatomy is not a good fit for the candidate, or the pair may just wish to try to help others by forming in a chain. procedures. The method of operating under scheduled Match Cycles was adopted. A Match Cycle begins with the running of the matching algorithm in the Canadian Transplant Registry (CTR) on a pre-announced date. Any activity pertaining to that match cycle takes into account only the pairs that were included on the Match Cycle date. This method allows for a new set of pairs to accumulate for the next Match Cycle; the rationale being that a larger group of pairs significantly improves the chances of finding matches for the very difficult-to-match pairs. Match Cycles are run three times a year to identify compatible matches between candidate and donor records in the Canadian Transplant Registry (CTR). Matches between registry candidates and donors are generated as groups or chains of donor exchanges each candidate receives a transplant in return for their incompatible donor donating to someone else in the chain. Chains are rated based on match points attributes (See Appendix 2) and the group of chains with the highest total points are proposed to move forward. There are three possible exchange formats. The Paired Exchange is the simplest and involves the matching of two incompatible pairs. Paired exchanges have resulted in 22 transplants during 2009 2013. The KPD Program is led and managed by Canadian Blood Services in collaboration with the provincial Living Donation and Transplant Programs across the county under shared operating guidelines, policies, processes and 7

The N-Way Exchange involves more than two pairs where the donor of the last pair must match the candidate of the first pair. During 2009-2013, 63 transplants were completed in 18 chains of 3, 4 or 5 pairs. The Domino Chain has been the most common format used and has resulted in the most number of transplants. It starts with a non-directed anonymous donor (NDAD) who donates to the candidate of an incompatible pair. The chain ends by having the donor of the last pair donate to a patient on the waitlist of the local transplant program where the NDAD originated. There were 186 transplants completed during 2009 2013 from 54 domino chains of 1 to 5 transplants each. Incompatible pairs who are not matched in a given match cycle and agree to remain in the Registry are carried forward into the next match cycle. 3.0 KPD Program Summary Since inception through 2013, the KPD Program has resulted in 218 transplants of candidates registered with the program, as well as 53 transplants of patients who were on local kidney waitlists for a total of 271 transplants (Figure 3.1). Table 1: KPD Program Activity 2009-2013 Total Number of Match Cycles 17 Pairs Registered 523 Candidates Registered* 491 NDADs Registered 64 Transplants Completed 271 Candidates Transplanted 218 Wait List Transplants 53 NDADs Donated 54 * A candidate may have several donors and each would be registered in the system as a unique pair 8

The program has seen a steady increase of registered candidate-donor pairs and NDADs as well as transplants since 2009. This comes from both the addition of new pairs in the Canadian Transplant Registry as well as the carry-over of pairs where candidates were not matched and are still waiting for a transplant. Figure 1: Registered Pairs and NDADs vs Registry Transplants by Year of Match Cycle 300 250 200 150 100 50 0 See Appendix 3: Additional Data for KPD Program Summary 2009 to 2013, for further information regarding this section including provincial activity and reasons why pairs have withdrawn from the Program (Table 3.1; Figures 3.2, 3.3, 3.4, 3.5, 3.6). 4.0 KPD Candidates and Donors For this report, statistics regarding age, sex, ABO-blood group, time on dialysis and HLA antibody levels are presented. 4.1 Age Registered Pairs Transplants NDADs 2009 2010 2011 2012 2013 The age of candidates ranged from 2 years of age to 76 years of age, with an average age of 48 years. Adults aged 40 to 69 made up 72% of the registered candidate population and received 78% of the total transplants. Pediatric patients ( 19 years of age) make up 2% of all candidates and 3% of all transplants. Seventy eight percent of pediatric registered candidates have been transplanted to the end of 2013. (Table 4.1.1) Donors were most commonly adults between the ages of 30 to 50 and this age range represented 89% of the registered donors. There were 9% of donors younger than 29 and only 2% of donors who were aged 70 or older. (Figure 4.1.1; Table 4.1.1) 4.2 Sex Over all age ranges, transplant candidates were almost evenly divided between male (47%) and female (53%). (Figure 4.2.1) Registered donors are 58% female and 42% male (Figure 4.2.2). NDADs are represented in the same ratio (58% female vs. 42% male). 4.3 Blood Group ABO blood grouping is a critical factor in identifying compatible matches between donors and candidates, as transplants between incompatible blood groups will most certainly result in organ rejection. ABO O candidates are overrepresented in the registry compared to ABO distribution in the general population, due to their requirement for an ABO O donor. (Figure 4.3.1). Table 2: Total Transplants Completed Between Donors and Recipients of Compatible Blood Groups for Years 2009-2013 A to A 71(33%) A to AB 3(1%) AB to AB 1(0%) B to B 34(16%) O to A 2(1%) 9

O to B 7(3%) O to O 100(46%) Total 218 Blood group O candidates made up 59% of all candidates but received only 46% of the transplants; only 35% of blood group O candidates received a transplant, compared with 57-67% of the other blood group candidates (Table 4.3.1). Blood group O candidates also take the longest time to match. For those that received a transplant, it took 231 days on average to receive a match proposal, compared to 135 days for group AB, 149 days for group A and 162 days for group B (Figures 4.3.2, 4.3.3). 4.4 HLA Antibody Levels Some candidates are incompatible with their registered donors (and other donors) due to antibodies to specific markers in the donor HLA antigens. These antibodies may form after exposure to foreign HLA antigens through previous transfusions, previous transplantations or pregnancies. They can be associated with high rates of kidney rejection or decreased longevity of the transplant. The percentage of the general population to which a candidate has antibodies is estimated as calculated panel reactive antibodies or c-pra. A candidate with a higher c-pra will be incompatible with more donors. Candidates with a c-pra of greater than or equal to 97% are the most difficult-to-match population in the Registry. Although representing 32% of all candidates since registry inception, these candidates have received only 11% of the transplants. Conversely, those with a c-pra of 95-96% were transplanted at rates equivalent to their prevalence in the candidate population. (Figure 4.4.2, Table 4.4.2) Patients with a cpra of > 97% represent an increasing proportion of candidates over time because these candidates are difficult to match and stay in the registry. Figure 2: Proportion of Candidates Participating in KPD Program 2009 to 2013 by cpra category 60% 50% 40% 30% 20% 10% 0% 2009 2010 2011 2012 2013 As of the last match cycle of 2013, 76 registered candidates (53%) had a c-pra greater than 97%. See Appendix 4: Additional Data for KPD Candidates and Donors for further information regarding this section. 5.0 Match Cycle Statistics cpra >97 cpra 95-96 cpra 51-94 cpra 1-50 cpra -0 5.1 Chain Length and Time to Completion Based on results over the years and on reasonable expectations for patients to make arrangements for surgery recovery time, once a match is proposed, the KPD Program s target is to complete a chain of transplants within 120 days from the time of chain proposal. The Program completed 63% of chains within this time frame and 81% within 150 days. Chain length is currently limited to 5 transplants due 10

to concern over the difficulty of logistics of surgeries in multiple transplant centres in a short time frame. There is no statistical difference in time to chain completion as it relates to chain length, and as a result, chain length limits are under review (Figures 5.1.1, 5.1.2, 5.1.3). Table 3: Chain Length and Median Time to Completion for Years 2009-2013 Number of candidates in chains N-way Chains Number of chains completed Median time to completion in days (Interquartile Range) 2 11 113 (63-121) 3 11 145 (85-161) 4 5 133 (124-167) review of the donor s medical chart, the candidate s team decides the donor is not a medically suitable match. In an attempt to reduce this type of decline, the Living Donation Advisory Committee has established a Kidney Paired Donation Protocol for Participating Donors which will be used, starting in 2015, by Living Donation Programs to assess all donors wishing to enroll in the Program. As well, the actual HLA cross-match performed before surgery may indicate that the candidate has a new antibody incompatibility to the donor which makes the transplant likely to be rejected (Figure 5.2.1; Tables 5.2.1). Finally, as with any medical procedure, and although rare in the KPD Program, a donor may change his/her mind at any time, causing a chain to collapse. Table 4: Reasons for Match Declines 2009-2013 5 2 115 (113-116) All N-ways 29 129 (93-162) Domino Chains Medical Total Donor NDAD Candidate 25 (43%) 16 3 6 2 11 104 (81-134) 3 18 100 (86-132) 4 14 100 (85-116) 5 11 127 (113-163) All Dominos 54 105 (87-133) All Chains 83 110 days (87 139) 5.2 Match Declines Not all proposed matches are accepted by the candidates centres. Matches can be declined for medical, non- medical, or surgical reasons. Medical declines result from the discovery of a medical issue that precludes the donor or candidate from continuing with the donation/transplant or when, after a thorough Non- Medical HLA * Surgical/ Anatomical 15 (25%) 7 5 3 15 (25%) 0 0 15 4 (7%) * positive cross-match or new DSA 3 0 1 In the event that a match is declined, an attempt may be made to repair the chain with a different pair. If this cannot be done, pairs from that chain will be included for matching when the algorithm is run again. Of the 134 proposed chains, 83 (62%) went to completion. The other 51 chains (38%) collapsed due to match declines. 11

5.3 Travel Human cells, tissues and organs that are to be used in transplantation are regulated under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations (CTO Regulations). The purpose of the CTO Regulations is to minimize the potential health risks to Canadian recipients of human CTO by addressing the safety in the processing and handling of these products. Under the CTO Regulations, the candidate s transplant program is responsible for the donor suitability assessment and safety of the kidney for transplantation (Cells, Tissues & Organs: Frequently Asked Questions Living Donor Transplant Program; Health Canada).To meet these standards, most transplant programs require the donor to travel to their centre for assessment prior to donating to the matched transplant candidate. Although the CTR program assigns points to matches between donors and candidates in the same city in an attempt to reduce the number of donors needing to travel, fifty three percent of matches have required either the donor or candidate to travel to the other person s province for surgery (Tables 5.3.1, 5.3.2). See Appendix 5: Additional Data for Match Cycle Statistics for further information regarding this section. 6.0 Outcomes 6.1 Program Performance Table 5: Candidate Disposition for KPD Program 2009 2013 Candidates transplanted through KPD Program 218 (44%) Candidates transplanted outside KPD Program Candidates not transplanted and still on Registry Candidate withdrawn from KPD Program* 61 (13%) 102 (21%) 110 (22%) Total 491 *Reasons why candidate-donor pairs have withdrawn are categorized in Table 6.1.1. 6.2 Recipient Outcomes A minimal set of date on outcome information is reported at one month and one year postsurgery for both donors and recipients. For 2009-2013, all donors and transplant recipients who had reached one year from date of surgery were alive (Tables 6.2.1a, 6.2.1b,Figure 6.2.1). Table 6: One Month Recipient and Graft Outcomes for All Recipients Who Had Reached One Year Post-Transplant 2009-2013 Patient Survival Graft Survival Rejection Episodes Registered Recipients Waitlist Recipients Total 216 (100%) 55 (100%) 271 (100%) 214 (99%) 55 (100%) 269 (99%) 12 (6%) 4 (7%) 16 (6%) As a national transplant data system evolves so will the ability to provide a robust analysis of all outcomes in Canada including the comparator groups as well as the subset of KPD Program patients. See Appendix 6: Additional Data for KPD Program Outcomes for further information regarding this section. 12

7.0 Conclusion For the period of 2009 2013, the KPD Program has resulted in 271 living kidney donor transplants. The transplants facilitated by the KPD program are immunologically low risk (ABO compatible and no DSA) for rejection. Without the KPD program, it is highly unlikely that these compatible transplant opportunities would have been identified; the incompatible pair candidates would either not have been transplanted or possibly placed on the deceased donor waitlist; or if transplanted with their incompatible donor, required more immunosuppression and incurred higher risk of rejection. The success of the KPD Program has demonstrated that inter-provincial collaboration and organ sharing in conjunction with a national web-based registry and a centrally managed and operated program can increase the number of transplant opportunities for those ESRD patients that have a donor willing to donate on their behalf so that they can in turn receive a medically suitable living kidney donor transplant from someone else. 13

Appendix 1: Glossary Table 1.1: Definition of Terms Term Definition ABO ABO Incompatible Active Actual Crossmatch Algorithm Antibody Antigen Calculated Panel Reactive Antibody (cpra) Canadian Transplant Registry (CTR) Candidate A general term which is used to identify the common human blood groups A, B, AB and O. For example, ABO-O is used to identify blood group O whereas ABO-B refers to blood group B. A circumstance where the donor and candidate blood groups are NOT compatible. Any donor or candidate record that is ready for matching in the Registry A test performed in an HLA laboratory to determine the compatibility between a candidate and potential donor. Mathematical formula and process which is used to determine potentially compatible candidates and donor pairs within the KPD Program. Known as a matching algorithm or VXM algorithm. (See Appendix 2) A protein molecule produced by the immune system in response to a foreign body (known as an antigen). A protein on a cell surface (in a donor kidney) which can cause the recipient immune system to react. A population based estimate of the percentage of donors that will be incompatible with a given candidate due to the presence of antibodies. An inter-provincial Listing and Allocation Platform and Service operated by Canadian Blood Services and presently supporting; the Kidney Paired Donation Program, the Highly Sensitized Patient Program (for kidney transplant candidates with high cpra) and the National Organ Waitlist (for non-renal transplant candidates). An End Stage Renal Disease patient who needs a kidney transplant and who is registered in the Canadian Transplant Registry. Candidate Disposition Candidate-Donor Pair Clinical outcome of a transplant candidate; may include such outcomes as transplant, no transplant or withdrawal from program. A transplant candidate and donor who are registered together in the KPD Program to find a suitable match for the transplant candidate through a 14

donor exchange. Closed Chain Compatible Match Cross Match Domino Chain Donor Donor Specific Antibodies (DSA) End Stage Renal Disease (ESRD) Flow Cytometry Crossmatch (FCXM) Graft Interquartile Range (IQR) Incompatible Pair Human Leucocyte Antigen (HLA) HLA Cross Match HLA Phenotype Kidney Paired Donation Program (KPD) Another term for N-Way Exchange. A transplant candidate and donor whose ABO blood and HLA types are compatible for transplantation. See Actual Cross Match, above. A chain of donor exchanges that begins with a Non Directed Anonymous Donor and ends with the last donor donating to a patient waiting for a kidney from the deceased donor waitlist. A person either living or deceased who provides cells, tissues or organs for transplantation. Recipient HLA antibody(ies) that match a given donor s HLA antigens. Lack of kidney function that requires a patient to require dialysis or transplant. A type of crossmatch test also known as Flow Crossmatch. Also called allograft, refers to a transplanted organ. In the case of KPD, refers to a transplanted kidney. A statistical measure of variability or statistical dispersion based on dividing a data set into quartiles. A transplant candidate and donor whose blood types and/or HLA tissue types are not compatible for transplant. A kidney transplant from the donor would be rejected by the candidate s antibodies. The antigens on the donor cell surface that may cause the recipient immune system to react. See also antigen, above. HLA antigens are named in groups or loci and identified as; A, B, Cw, DR, DRw, DQA, DQ, DPA, and DP. See Actual Crossmatch A detailed description of the HLA antigens in a candidate or donor. Used as a basis for matching donors and recipients. The program operated and managed by Canadian Blood Services in collaboration with the provincial Living Kidney Donation and Transplant Programs in which candidate-donor pairs and Non-Directed Anonymous 15

Donors are registered for the purposes of attempting to find compatible living kidney donors for the candidates through a matching algorithm. Living Paired Donor Exchange (LPDE) Loci Match Cycle N-Way Exchange Non Directed Anonymous Donor (NDAD) Non-preemptive Candidate Non-terminal Position Paired Exchange Positive Cross Match Potential Donor Pre-emptive candidate Recipient Terminal Pair Transplant Candidate A program initiated in 2008 and now referred to as the Kidney Paired Donation Program, see above. The genetic region of DNA coding for the proteins in one of the HLA groups. See also HLA, above. The time period which commences with the running of a matching algorithm and extends until the next matching algorithm is initiated. Match cycle dates are announced at the beginning of the calendar year an all activity within the Match Cycle uses only the pairs that were enrolled on the Match Cycle date. A combination of transplant candidate-donor pairs in which there are more than 2 pairs where the donor of the last pair must match the transplant candidate of the first pair. An unidentified individual who is willing to donate a kidney to anyone in need. A transplant candidate who is currently on dialysis. Any pair in a domino chain that is not the last pair in the chain. A matching of two compatible transplant candidate-donor pairs where the transplant candidate receives a kidney from the donor of the other pair. A crossmatch test result where the transplant candidate is not compatible with the donor (high risk of organ rejection). A donor who has agreed to donate a kidney if a matching candidate can be found. A candidate who is not yet on dialysis. The goal is to pre-empt the need for dialysis with a kidney transplant. A patient who has received a cell, tissue or organ transplant. The last candidate-donor pair at the end of a domino chain. The donor of this pair will donate to a candidate on a local deceased waitlist. An End Stage Renal Disease patient who needs a kidney transplant and who is registered in the Canadian Transplant Registry. Also referred to as a Candidate, see above. 16

Virtual Crossmatch (VXM) Waitlist A comparison between candidate antibodies and donor antigens, (see Antigen and Antibodies, above). A positive VXM means the candidate antibody(ies) matches the donor antigen with a high risk of organ rejection. A negative VXM means the recipient antibody(ies) do NOT match the donor antigen with a corresponding lower risk of rejection. A list of patients who are qualified and registered by a transplant program and who are waiting to receive an organ transplant. 17

Appendix 2: Matching Algorithm Table 2.1 Matching Points* Match points are allotted to matches between donor and candidate records with the following characteristics: Match Point Attribute Proposed Any acceptable candidate-donor match (using ABO, HLA, match filters) 100 Highly sensitized candidate (cpra > 80%) 125 ABO match O to O 75 Pediatric candidate 75 Candidate is prior living donor 75 ABDR O/6 mismatch 75 Dialysis wait time (starting at initiation of dialysis) Days/30 Geography: same city 25 Donor/Candidate age difference of < 30 years 5 ABO match: A to A, B to B, AB to AB 5 EBV negative to negative match 5 *Kidney Transplant Advisory Committee Matching Review, September 25, 2012 Guiding Principles for Kidney Paired Donation Program The KPD Program policies, procedures, processes and guidelines are developed under these principles: 1. Maximize Transplants primary goal should be to find the greatest number of high quality matches between living donors and recipients. 2. Maximize Logistics to the extent possible, the need for donors or recipients to travel should be minimized. 3. Equity for High Need Patient Groups any candidates who are disadvantaged due to medical or demographic factors should receive additional priority. (e.g, highly sensitized, blood group O, pediatrics, lengthy time on dialysis, etc.). 4. Priority for Higher Quality Matches transplants that are zero mismatch HLA, A, B, DR or other clinical criteria considered to be more ideal should receive special priority. 18

5. Evidence-Based Decision Making all principles adopted and algorithm decisions made should be based on the most current and best quality peer reviewed evidence available. 19

Appendix 3: Additional Data for KPD Program Summary 2009 to 2013 Figure 3.1: Chain Types and Transplants Completed in the KPD Program 2009-2013 Non-Directed Anonymous Donors (NDADs) continue to be a key success factor for increasing transplant volumes. Fifty four NDADs contributed to 186 registry candidates and 53 waitlist recipients receiving a transplant - one NDAD donation resulted in a reported immediate technical failure; because the rest of the chain did not proceed and a waitlisted patient did not get transplanted, there is one less waitlist transplant than NDADs who donated. Additionally, 30% of all transplant activity in the Program has been achieved through paired exchanges or closed chains. Figure 3.2: KPD Program Activity by Match Cycle 2009-2013 In 2013, 128 new pairs participated, increased from 113 in 2012 and 95 in 2011. However, total numbers of pairs participating in each match cycle remain static since the end of 2012. 20

Figure 3.3: Candidates and Transplant Recipients by Province 2009-2013 *n=218 Transplants; 491 Candidates Figure 3.4: Candidates and Transplant Recipients by Province per Million Population (PMP) 2009-2013 21

Figure 3.5: Annual Totals For Candidates and Transplant Recipients Per Million Population by Province 2009-2013 22

The transplants facilitated by the KPD Program are immunologically low risk (ABO compatible and no DSA) for rejection. Without the KPD Program, these compatible transplants would not have been identified; the incompatible candidate-donor pairs would either have not have been transplanted and possibly placed on the deceased donor waitlist, or if transplanted with their incompatible donor, required more immunosuppression and incurred higher rejection risk. Non-KPD living donation activity (per million population) in Canada has been static since 2008. (Source: CORR Annual Report 2013) Table 3.1: System Performance for Matches Transplanted and Proposed Chains Completed KPD Total 2009 2010 2011 2012 2013 # of Unique Proposed Matches # of Proposed Matches Transplanted % of Proposed Matches Transplanted* 361 28 67 82 75 109 218 19 37 49 48 65 60% 68% 55% 60% 64% 60% # of Proposed Chains 134 12 25 25 30 42 # of Completed Chains 83 8 17 15 20 23 % of Proposed Chains Completed 62% 67% 68% 60% 67% 55% * 60% of all unique candidate/donor matches proposed have proceeded to transplant Figure 3.6: Annual Transplants Facilitated versus Initial Predicted Target 2009-2013 120 100 80 60 40 20 0 Registered Recipients Wait List Recipients Predicted Target = 109 17 4 13 9 67 3 35 40 41 7 14 21 2009 2010 2011 2012 2013 2014 23

Appendix 4 Additional Data for KPD Candidates and Donors The supplemental data in this appendix is presented as per Section 4, KPD Donors and Candidates. Section 4.1 Age Table 4.1.1: Age Range of Donors and Non-Directed Anonymous Donors 2009-2013 n(% ) Registered Donors Non-Directed Anonymous Donors Total Female Male Total Female Male All Ages 523 (100%) 305 (58%) 218 (42%) 64 (100%) 37 (58%) 27 (42%) Aged 18-29 48 (9%) 20 (4%) 28 (5%) 3 (5%) 2 (3%) 1 (2%) Aged 30-39 106 (20%) 62 (12%) 44 (9%) 7 (11%) 4 (6%) 3 (5%) Aged 40-49 146 (28%) 95 (18%) 51 (10%) 18 (28%) 9 (14%) 9 (14%) Aged 50-59 145 (28%) 88 (17%) 57 (11%) 22 (34%) 16 (25%) 6 (9%) Aged 60-69 76 (15%) 40 (7%) 36 (7%) 12 (19%) 6 (10%) 6 (9%) Aged 70+ 2 (0%) 0 (0%) 2 (0%) 2 (3%) 0 (0%) 2 (3%) Figure 4.1.1: Age of Candidates, Transplant Recipients and Waitlst Recipients n(%) for 2009-2013 24

Section 4.2 Sex Figure 4.2.1: Distribution of Candidates by Sex and Age for 2009-2013 90 20% 80 70 60 50 40 30 20 10 0 16% 13% 12% 13% 10% 9% 7% 6% 6% 4% 1% 1% 1% 1% 19 20-29 30-39 40-49 50-59 60-69 70+ 18% 16% 14% 12% Female 10% Male 8% 6% 4% 2% 0% Note: per cents refer to percentage of total candidates Figure 4.2.2: Distribution of Donors by Sex and Age for 2009-2013 120 18% 17% 100 20% 18% 16% 80 60 40 20 0 12% 10% 11% 9% 7% 7% 5% 4% 1% 0% 18-29 30-39 40-49 50-59 60-69 70+ 14% 12% Female 10% Male 8% 6% 4% 2% 0% Note: per cents refer to percentage of total donors 25

Section 4.3 Blood Group Figure 4.3.1: ABO Blood Group Distribution of Candidates Participating in Each Match Cycle For 2009-2013 as Compared to the Canadian Population Table 4.3.1: KPD Program Transplant Recipients by Blood Group for 2009-2013 n(%) Total A AB B O Total Recipients Transplanted 218 73 (33%) 4 (2%) 41 (19%) 100 (46%) ABO Distribution in Candidate Pool 491 128 (26%) 6 (1%) 70 (14%) 287 (59%) % of ABO Group Transplanted 44% 57% 67% 59% 35% Total Waitlist Recipients Transplanted 53 35 (66%) 8 (15%) 9 (17%) 1 (2%) ABO-O candidates remain in the registry at a greater prevalence than ABO-O individuals in the Canadian population, driven in part by registration of ABO incompatible pairs; ABO incompatible pairs are more likely to have an ABO-O candidate, and since these candidates can receive only from an ABO-O donor, they have fewer potential match opportunities. 26

Blood group O candidates represent 59% of the candidate population yet receive 46% of the transplants. However, of 171 pairs that have withdrawn from the registry, 70% had an ABO-O candidate, resulting in a relatively stable level of active ABO-O candidates in the registry. The discrepancy between ABO-O candidate transplant rate, 35%, and non-abo-o candidate transplant rates, 57-67%, demonstrates the systemic disadvantage to ABO-O candidates. Strategies being discussed and explored to mitigate this disadvantage include allocating ABO-A donors with a non-a1 subtype to ABO-O candidates and doing ABO incompatible transplants in high cpra ABO-O candidates. Figure 4.3.2: Median Wait Time in Days* to Receiving a Match Proposal by Blood Group For Candidates 2009-2013 *Median wait times (days) to transplant parallel the lower match and transplant rates of ABO-O candidates (p=0.004) Median [IQR] (n = 218) Figure 4.3.3: Median Wait Time in Days By Blood Group Since First Match Cycle Participation for Currently Active Candidates Who Have Not Been Transplanted 2009-2013 (p=0.427) Median [IQR] (n =98) 27

Section 4.4 HLA Antibody Levels Table 4.4.1: Time-on-Dialysis in Months to Transplant for Candidates and Waitlist Recipients For 2013 and As Compared to 2009-2013 n(%) Total Candidates Transplanted Total 0 1 to 12 13 to 24 25 to 36 37+ 218 65 (30%) 37 (17%) 36 (16%) 32 (15%) 48 (22%) Total Wait List Recipients Transplanted 53 1 (2%) 3 (6%) 8 (15%) 3 (6%) 38 (71%) Figure 4.4.1: Proportion of 218 Transplant Recipients in Each Months-on-Dialysis Category by cpra for Years 2009-2013 Those transplant recipients with dialysis times >36 months, are more likely to have cpra>95%. Below 36 months dialysis time, cpra does not impact wait time. The months-on-dialysis of the active KPD candidates at the end of the reporting period are reflective of local waitlist candidates and allocation practises and not reported here. 28

Figure 4.4.2: Distribution of cpra for Candidates by Match Cycle for Years 2009-2013 Candidates with cpra 97% have increased in prevalence in the Canadian Transplant Registry and presently represent 53% of active candidates. Conversely, candidates with cpra 95-96% have decreased in prevalence in this registry over time. Table 4.4.2: cpra Categories for Candidates and Transplant Recipients 2009-2013 n(%) 0 1%-50% 51%-94% 95%+ 95%-96% 97%+ Total Transplanted 49 (22%) 55 (25%) 79 (36%) 35 (17%) 12 (6%) 23 (11%) Not Transplanted 45 (16%) 45 (16%) 37 (14%) 146 (54%) 11 (4%) 135 (50%) Total Candidates in cpra Group % of cpra Group Transplanted 95 (19%) 99 (20%) 116 (24%) 181 (37%) 24 (5%) 157 (32%) 52% 56% 68% 19% 50% 15% The most disadvantaged population in the Canadian Transplant Registry is candidates with a cpra 97%. Although representing 32% of all candidates since registry inception, candidates with cpra 97% have received only 11% of all transplants. Conversely those with cpra of 95-96% are transplanted at the same or greater proportion as candidates in other cpra categories, and at a rate equivalent to their presence in the candidate population. 29

Table 4.4.3a: Blood Group of Donors to Blood Group of Recipients 2009-2013 n(%) A to A A to AB AB to AB B to B O to A O to B O to O Total 71 (33%) 3 (1%) 1 (0%) 34 (16%) 2 (1%) 7 (3%) 100 (46%) 218 Table 4.4.3b: ABO-O Group of Candidates Registered and Transplanted by cpra 2009-2013 n(%) 0% 1% - 50% 51% - 94% 95% - 96% 97%+ Candidates 65 (23%) 62 (22%) 62 (22%) 12 (4%) 86 (29%) Transplanted 21 (21%) 22 (22%) 40 (40%) 5 (5%) 12 (12%) Transplant Rate 32% 35% 65% 42% 14% Percent of cpra Category Transplants that are Blood Group O Recipients 43% 40% 51% 42% 52% Higher cpra does not appear to disadvantage ABO-O candidates any more than other blood groups. 29% of all ABO-O candidates have cpra 97% but receive 14% of the ABO-O transplants. This is similar to the 32% of the overall candidate population with cpra>=97% who receive 11% of transplants (table 4.4.2) 30

Appendix 5 Additional Data for Match Cycle Statistics The supplemental data in this appendix is presented by section as per Section 5, Match Cycle Statistics. Section 5.1 Chain Completion Figure 5.1.1: Median Days to Transplant Chain Completion by Chain Type and Length for 2009-2013 Median [IQR], p=0.203 Figure 5.1.2: Number of Days to Chain Completion by Type of Chain for Years 2009-2013 (p=0.316 for median time across groups) 31

Figure 5.1.3: Days to Completion by Chain Length for Years 2009-2013 (p=0.216 for median time across groups) The KPD Program target is to complete chains within 120 days from time of proposal. This was achieved 63% of the time while 81% of chains were completed within 150 days. Figure 5.1.4: Median Days [IQR] from Enrollment and Date of Proposal to Date of Surgery for NDAD Versus Registered Donors Who Donated 2009-2013 NDADs most commonly proceed to transplant within the same match cycle in which they enroll; median time to transplant from enrollment and proposal is similar. Once proposed, donors proceed to transplant within the same median time as NDADs, however the time from enrollment to proposal can be more variable, depending on their ABO and HLA phenotype, as well as the likelihood of matching of their corresponding registered candidate. For donors remaining in the Registry, median wait time is in excess of a year. 32

Figure 5.1.5: Position in Completed Domino Chains of Donors by ABO Group For Years 2009-2013 *n= 132 KPD Program donors It is uncommon for a chain to end (terminal position) with an ABO-O donor; the only one to date has been due to a terminal pair being removed from the chain just prior to transplant. Conversely, ABO-AB donors have, to date, always been in the terminal position, donating to the waitlist. Forty three percent of blood group A donors were in a non-terminal position of domino chains, thereby contributing to initiation or extension of domino chains. Similarly 69% of ABO-B donors in domino chains are in a nonterminal position. Registered pairs with a blood group A or B donor may be reassured that substantial transplant opportunities are possible for the non-blood group O donor. Section 5.2- Donor Disposition Figure 5.2.1: Donor Disposition and Number of Match Cycles in Which They Participated 2009-2013 33

Of those donors who remain in the KPD registry as of December 31, 2013, a majority have been in fewer than 6 match cycles (~ 2 years). Similarly, of those who withdrew from the Registry, the majority also participated in less than 6 match cycles. Table 5.2.1: Accuracy of Prediction of Flow Crossmatch (FCXM) by Virtual Crossmatch (VXM) Category 2009 2010 2011 2012 2013 Number of actual crossmatches performed 25 69 56 70 61 Number of unexpected actual positive FCXM and/or new DSA 3 5 5 1 1 Percent of unexpected positive FCXM and/or new DSA 12% 7% 9% 1.4% 1.6% All matches are proposed based upon a negative virtual crossmatch (VXM) predicting a negative actual flow crossmatch (FCXM) plus the absence of donor-specific antibody (DSA). Reasons for the 15 positive VXM and/or new DSA in 2009-2011 included: antibodies to DP and DQA (prior to these loci becoming standard in the VXM in late 2011), DSA misidentified at registration, or new DSA detected on final testing but not present at registration. Beyond 2011, antibodies to DP and DQA were included in the VXM algorithm and no longer contribute to the unexpected positive crossmatch rate, and strategies have been implemented to ensure standardized antibody reporting and reduction in misidentified DSA. The low rate of unexpected positive FCXM and/or new DSA in the last two years is superior when benchmarked against VXM performance in other settings.* *Nikaein A, Cherikh W, et al. Transplantation. 2009;87(4):557-62.; Tambur AR, Ramon DS, et al. AJT. 2009;9(8):1886-93. 34

Section 5.3 Travel Forty-eight percent of the matches required either the donor or candidate to travel to the other person s transplant center for the surgeries. Table 5.3.1: Donors required to Travel Inter-provincially 2009-2013 Matched Pairs Donor who Travelled Donor Travel Rate Transplanted 129 271 48% Table 5.3.2: Summary of Inter-Provincial Transplants for 2009 2013 Transplant Centre Province BC AB SK MB ON QC NS Donor Out BC to 7 1 2 15 3 1 29 AB to 5 2 2 6 2 2 19 SK to 2 2 1 4 1 1 11 MB to... 4 0 0 3 0 2 9 ON to 17 9 1 4 6 3 40 QC to 5 2 0 0 4 2 13 NS to 1 1 0 0 6 0 8 Donor In 34 21 4 9 38 12 11 129 35

Appendix 6 Additional Data for KPD Program Outcomes The supplemental data in this appendix is presented by section as per Section 6, Outcomes. Section 6.1 Participant Withdrawal Table 6.1.1: Reasons Candidate-Donor Pairs Have Withdrawn from the KPD Program Received Transplant from Another Source Donor or Candidate Medical Reason Donor or Candidate Non-Medical Reason KPD Total 2009 2010 2011 2012 2013 61 7 12 15 18 9 41 2 7 3 12 17 53 4 7 9 14 19 Reason not Provided 17 4 0 1 3 9 Total Pairs 563* 84 155 182 231 246 Participating *The total pairs participating is less than the sum of the yearly totals because unmatched pairs can be carried forward through multiple match cycles and are counted only once as ever participating. Section 6.2 Recipient Outcomes Table 6.2.1a: Outcome Results for 186 KPD-registered Recipients Reaching One-Month Post-Transplant n(%)( Donor Survival 100% (N=271)) Waitlist Recipients Recipients Total Patient Survival 216(100) 55(100) 271(100) Graft Survival 214(99) 55(100) 269(99) Rejection Episode 12(6) 4(7) 16(6) Creatinine Level* µmol/l < 100 87(41) 16(29) 103(38) 100-149 92(43) 28(51) 120(45) 150-174 20(9) 6(11) 26(10) 175-199 6(3) 3(5) 9(3) >199 9(4) 2(4) 11(4) *The maximum creatinine level ranged from 683 to 18 with a mean of 116 and a median of 112 µmol/l. 36

Table.2.1b: Outcome Results for 186 KPD-registered Recipients Reaching One-Year Post-Transplant n(%) (Donor Survival 100% (N=186)) Waitlist Recipients Recipients Total Patient Survival 148(100) 38(100) 186(100) Graft Survival 144(97) 38(100) 182(99) Rejection Episode 13(9) 2(5) 15(6) Creatinine Level* µmol/l < 100 64(44) 10(26) 74(41) 100-149 63(44) 23(61) 86(47) 150-174 11(8) 4(11) 15(8) 175-199 3(2) 0(0) 3(2) >199 3(2) 1(3) 4(2) *The maximum creatinine level ranged from 220 to 29 with a mean of 109 and a median of 111 µmol/l. Figure 6.2.1: Patient and Graft Survival for Recipients with minimum one year follow-up 100% 99% 98% 97% 100% 100% 99% 98% 223 173 123 73 23 96% n = 186 n = 186 n = 184 n = 182-27 1 Month 1 Year 1 Month 1 Year Patient Survival Graft Survival Outcome information is reported only on the 191 donors and 191 transplant recipients that have reached one year from the time of donation or transplant. At December 31, 2013, all but one transplant recipient and all donors who had reached one year from date of surgery were alive. Graft survival at one month post-transplant for this cohort was 99% and one year graft survival was 97%. 37