Pre- and postdonation kidney function in donors of a kidney paired donation with unique criteria for donor glomerular filtration rate - a longitudinal cohort analysis.

Baseline predonation estimated GFR (eGFR) appears to predict the risk of postdonation chronic kidney disease in live donors. New KIDGO guidelines recommend an eGFR ≥90 ml/min/1.73 m2 as an acceptable level of glomerular filtration rate (GFR) for kidney donation. In the Australian Paired Kidney Exchange (AKX) program, all donors with a raw measured GFR (mGFR) ≥80 ml/min are deemed suitable for donation, but the significance of this selection indicator is unclear. We analysed the first 129 live donors in the AKX program with at least 1-year follow-up linking records in the AKX database and ANZDATA. There were 73 male and 56 female donors; mean (±SD) age was 53 ± 11 years. Predonation eGFR was 94 ± 13 ml/min/1.73 m2 , mGFR 99 ± 17 ml/min/1.73 m2 and raw mGFR 108 ± 18 ml/min. Baseline eGFR was <80 ml/min/1.73 m2 in 19 donors, and <90 ml/min/1.73 m2 in 42 donors. At 1 year postdonation eGFR was 68 ± 15 ml/min/1.73 m2 and the predicted eGFR at 30 years postdonation was on average 50 (29-83) ml/min/1.73 m2 . The hypothetical mean age at end-stage kidney disease was estimated to be 145 (95% CI 120-263) years. Over 30% of AKX live donors would have been excluded from donation using KDIGO guidelines. Using AKX donor guidelines, the majority of donors with predicted eGFR <30 ml/min/1.73 m2 30-year postdonation were aged ≥50 years. Long-term outcome data on AKX donors with low eGFR will need careful monitoring.

Challenges of kidney paired donation transplants involving multiple donor and recipient surgeons across Australia.

BACKGROUND: The Australian kidney paired donation program adopted the principles of within-chain simultaneous live donor surgery and of organ transport, with the requirement of keeping cold ischemia time (CIT) to <12 h. Whether these principles could be adhered to and what impact on transplant outcome they might have is unknown. METHODS: We evaluated the logistic challenges and outcomes of the first 100 kidney transplants performed in the Australian kidney paired donation program. RESULTS: Within 4 years, 17 donor surgeons at 12 centres were involved in 37 chain exchange surgeries. Sixteen kidneys were transplanted at the same hospital and 84 required transport to the recipient hospital. Mean (±SD) within chain anaesthetic induction time variability was 8 ± 18 min and mean individual surgeon operating time was 115 ± 44 min. In two cases, delays during donor surgery resulted in increased CIT by 1 h because of deferred transport. CIT was 2.6 ± 0.6 h for non-shipped and 6.8 ± 2.8 h for shipped kidneys, four kidneys had CIT of 12-14 h. Immediate allograft function was observed in 85% of recipients, with no difference between shipped and non-shipped kidneys. There were only two cases of delayed graft function requiring temporary dialysis; both had CIT <7 h. There was no difference in serum creatinine at 1 month between non-shipped and shipped kidneys (105 ± 26 versus 112 ± 50 µmol/L) and allograft survival at 1 year was 97%. CONCLUSION: The study provided a favourable audit of kidney transplant activity, despite challenges of simultaneous surgery, organ transport coordination and prolonged CIT. The decision to ship donor kidneys rather than the donor was demonstrated to be feasible and safe.

Providing Better-Matched Donors for HLA Mismatched Compatible Pairs Through Kidney Paired Donation.

BACKGROUND: Participation of compatible pairs (CP) in kidney paired donation (KPD) could be attractive to CPs who have a high degree of HLA mismatch, if the CP recipient will gain a better HLA match. Because KPD programs were not designed to help CP, it is important to define allocation metrics that enable CP to receive a better-matched kidney, without disadvantage to incompatible pairs (ICP). METHODS: Simulations using 46 ICPs and 11 fully HLA-mismatched CPs were undertaken using the Australian KPD matching algorithm. Allocations were preformed adding 1 CP at a time or all 11 CPs at once, and with and without exclusion of unacceptable antigens selected to give a virtual calculated panel-reactive antibody ranging 70% to 80% to improve HLA matching in CP recipients. RESULTS: On average, most CP recipients could be matched and had a lower eplet mismatch (EpMM) with the matched donor (57 ± 15) than with their own donor (78 ± 19, P < 0.02). However, only recipients who had an EpMM to own donor greater than 65 achieved a significant reduction in the EpMM with the matched donor. The gain in EpMM was larger when CPs were listed with unacceptable antigens. Furthermore, inclusion of 1 CP at a time increased matching in ICP by up to 33%, and inclusion of all 11 CPs at once increased ICP matching by 50%. CONCLUSIONS: Compatible pair participation in KPD can increase match rates in ICP and can provide a better immunological profile in CP recipients who have a high EpMM to their own donor when using allocation based on virtual crossmatch.

Outcomes of kidney paired donation transplants in relation to shipping and cold ischaemia time.

To assess the impact of shipping distance and cold ischaemia time (CIT) of shipped organs in a kidney paired donation (KPD) programme, we evaluated the outcomes of the initial 100 kidney transplants performed in the Australian KPD programme. In a 44-month period, 12 centres were involved in fifteen 2-way, twenty 3-way, one 4-way and one 6-way exchanges. Sixteen kidneys were transplanted at the same hospital (CIT 2.6 ± 0.6 h) and 84 required transport to the recipient hospital (CIT 6.8 ± 2.8 h). A spontaneous fall in serum creatinine by at least 10% within 24 h was observed in 85% of recipients, with no difference between nonshipped and shipped kidneys. There were two cases of transient delayed graft function requiring dialysis and patient and graft survival at 1 year were 99% and 97%, respectively. There was no difference in recipients of nonshipped compared with shipped kidneys with regard to serum creatinine at 1 month (mean difference (MD) 7.3 µmol/l, 95% CI -20.2 to 34.8, P = 0.59), 1-year graft survival (MD 3.9%, 95% CI -5.4 to 13.2, P = 0.41) or patient survival (MD -2.4%, 95% CI -10.0 to 5.2, P = 0.54). Despite prolonged CIT for interstate exchanges, the programme's decision to ship donor kidneys rather than the donor appears to be safe.

Four years of experience with the Australian kidney paired donation programme.

New approaches to increase kidney transplantation rates through expansion of live donor kidney transplantation have become necessary due to ongoing shortage of deceased donor organs. These strategies include desensitization in antibody-incompatible transplants to overcome the barrier of blood group incompatibility or human leucocyte antigen antibodies between recipient and donor and kidney paired donation (KPD) programmes. In KPD, a kidney transplant candidate with an incompatible live donor joins a registry of other incompatible pairs in order to find potentially compatible transplant solutions. To match the largest possible number of donor-recipient pairs while minimizing immunologic risk, KPD programmes use sophisticated algorithms to identify suitable matches with simultaneous two-way or more complex multi-way exchanges as well as including non-directed anonymous donors to start a chain of compatible transplantations. Because of the significant immunologic barriers when fewer donor options are available, the optimal solution for difficult-to-match, highly sensitized patients is access to more potential donors using large multi-centre or national KPD registries. This review focuses on the first 4 years of experience with the Australian multi-centre KPD programme that was established in October 2010.

ABO-incompatible matching significantly enhances transplant rates in kidney paired donation.

BACKGROUND: Although preformed donor-specific anti-human leukocyte antigen antibodies (DSA) can be overcome by plasmapheresis-based strategies with some success in renal transplantation, kidney paired donation (KPD) is a more effective strategy to avoid DSA. In contrast, ABO incompatibility can be crossed with outcomes equivalent to ABO-compatible transplantation. Here, we report the ability of accepting human leukocyte antigen-compatible but ABO-incompatible donors to increase the number of exchanges in a KPD program. METHODS: In the Australian KPD program, virtual crossmatch is used to allocate suitable donors to recipients. Acceptance of ABO-incompatible donors is allowed in cases where anti-blood group antibody titres are deemed amenable to removal by apheresis or immunoabsorption. The number of matched recipients, identified chains, and transplants performed with and without acceptance of ABO incompatibility was analyzed. RESULTS: In 2 years, 115 pairs were included in nine quarterly match runs. Incompatibility due to DSA accounted for 86% of the listed pairs and 52% were also blood group incompatible to their coregistered donor. Median calculated panel-reactive antibody in registered recipients was 83% (mean, 67%±37%). ABO-incompatible donors were accepted for 36 patients. Two waitlist recipients and 48 KPD candidates were matched and transplanted. Ten recipients (20%) of an ABO-incompatible donor kidney were distributed across 8 chains that resulted in 21 recipients being transplanted. Thus, without ABO-incompatible matching, only 27 recipients in 12 chains would have been transplanted. CONCLUSION: Acceptance of blood group-incompatible donors for patients with low to moderate anti-blood group antibody significantly increases transplant rates for highly sensitized recipients.

Comparison of time on the deceased donor kidney waitlist versus time on the kidney paired donation registry in the Australian program.

In the Australian kidney paired donation (KPD) program matching is based on acceptable mismatches, whereas deceased donor waitlist (DDWL) patients are allocated kidneys based on HLA antigen matching rules. Herein, we compared waiting time for a KPD match to the waiting time on the DDWL and the occurrence of matching in the DDWL for patients who were registered in both programs. Data on first dialysis, matches on the DDWL, KPD program entry, matches and transplant dates were assessed in 26 KPD recipients of the Australian program. There were 22 recipients who were listed in the DDWL and received kidney transplants by KPD. Time on dialysis until KPD transplantation was 808 ± 646 days. Eleven patients had never been matched with a deceased donor (waiting time 345 ± 237 days) and 11 had been matched on average 3 ± 5 times (waiting time 1227 ± 615 days, P < 0.0001 vs. never matched), but did not progress to transplantation because of positive crossmatch or class II donor-specific antibody. Mean time from registration in the KPD program until kidney transplantation was 153 ± 92 days (P < 0.0001 vs. DDWL). KPD allocation using the acceptable mismatch approach is effective in identifying suitable live donors for some recipients within a relatively short time-frame.

High transplant rates of highly sensitized recipients with virtual crossmatching in kidney paired donation.

BACKGROUND: In kidney paired donation (KPD), flexibility in the allocation of incompatible pairs is required if a critical mass of pairs to efficiently find matches cannot be reached. METHODS: In the Australian KPD program, virtual crossmatch is used for the allocation of suitable donors to registered recipients. Matching is based on acceptable mismatches, and donors are excluded from matching to recipients with donor-specific antibodies (DSAs) greater than 2000 mean fluorescence intensity (MFI). Match and transplant rates in the first year of the program were reviewed with respect to recipient and donor characteristics, including blood group distribution, level of recipient's sensitization, and postallocation crossmatches. RESULTS: Four quarterly match runs were performed, which included 53 pairs and 2 altruistic donors. Human leukocyte antigen incompatibility accounted for 90% of the listed pairs. In the second run, the DSA threshold was increased to greater than 8000 MFI, because no matches were found with standard allocation. Optional ABO-incompatible matching was introduced from run 3. Matches were identified in 37 (70%) patients, of whom 92% had a negative crossmatch with their matched donor. Crossmatch positive results were found only in recipients with DSAs greater than 2000 MFI in the second run. In 4 cases immunological reasons and in 4 cases other reasons resulted in breakdown of chains and 17 patients not progressing to transplantation. Eventually, 20 (38%) patients received a KPD transplant, and 35% of these had a calculated panel-reactive antibody greater than 90%. CONCLUSIONS: KPD using virtual crossmatch is a valid and effective solution for patients with immunologically incompatible donors even in the context of highly sensitized recipients.

Paired kidney donations to expand the living donor pool: the Western Australian experience.

Falling numbers of deceased organ donors and longer kidney transplant waiting lists have increased the emphasis on live kidney donation to meet demand for kidney transplantation. Several new strategies have been introduced to expand live donation beyond the classic direct donation. These include: altruistic donation; paired kidney exchange (PKE); and altruistic donor chains programs. Using incompatible donor-recipient pairs and altruistic donors, the Western Australian PKE program achieved nine successful kidney transplantations between October 2007 and November 2008. If PKE were performed routinely in Australia, the rate of kidney transplants could increase by 7%-10%.