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Deceased Donor Kidney Transplantation in New Caledonia

A Unique Collaboration With Australia

Delezire, Arnaud MD1; Celton, Jean-Louis MD2; Touzain, Frederic MD2; Biche, Veronique BN3; Haidar, Fadi MD4; Cantin, Jean-François MD4; Tivollier, Jean-Michel MD4; Mesguen, Caroline MD4; Carceles, Odette MD5; Lamy, Thomas MD5; Saidi, Kader MD5; Allen, Richard FRACS6; Chadban, Steven MBBS, PhD6; Gracey, David MBBS, PhD6; Laurence, Jerome FRACS6; Verran, Debbie FRACS6; Mawson, Jane BN6; Wyburn, Kate MBBS, PhD6; Quirin, Nicholas MD5

Author Information
doi: 10.1097/TP.0000000000002859
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New Caledonia is a French territory with 269 000 inhabitants,1 located in the South-Pacific 1210 km east of Australia and 20 000 km from France (Figure 1). The islands have the fourth highest incidence of end-stage kidney disease (ESKD) in the world.2 In 2016, the incidence of newly treated ESKD was approximately twice that of France.3 Diabetic nephropathy is the leading cause (34%) of ESKD, followed by chronic glomerulonephritis (14%) and hypertensive glomerulopathy (9%).

FIGURE 1
FIGURE 1:
Geographic distance of New Caledonia to several other countries, its proximity to Australia, allowing the establishment of a collaborative transplant program.

The high incidence of ESKD is likely related to the high prevalence of obesity, estimated to be approximately 27% in addition to diabetes mellitus and hypertension. Despite the high incidence of kidney disease and relative ease of access to dialysis, opportunities for kidney transplantation in Noumea have been limited.

THE NEED FOR A NEW CALEDONIAN DECEASED DONOR PROGRAM

Before 2012, there were only 2 options available to New Caledonian ESKD patients to access kidney transplantation: (1) a live-donor kidney transplant in Sydney (or occasionally in France) or (2) moving to France to await a deceased donor kidney transplant. The latter involved leaving New Caledonia for the duration of the waiting time, with significant social, cultural, and professional disruption. Economic costs were also significant for New Caledonia’s Health System, which financed the extended stay in France.4

In 2012, New Caledonia started to collaborate with Royal Prince Alfred Hospital in Sydney, Australia to establish a local deceased donor kidney transplant program, building on the preexisting relationship between the 2 centers. Aims of the New Caledonian deceased donor transplant program were to (1) increase access to kidney transplantation locally for New Caledonian patients, (2) shorten the time spent out-of-territory, (3) reduce the economic burden of ESKD for New Caledonia, and (4) improve the chances of favorable immunologic matches by taking advantage of donor/recipients from a similar genetic background. Obviously, this approach required a deceased donor organ retrieval program in New Caledonia.

The French Agence de la Biomédecine (ABM), which oversees organ retrieval and transplantation in France accredited Noumea’s main hospital, the Centre Hospitalier Territoire (CHT), to facilitate local organ retrieval and allocation. A convention was adopted between ABM and New Caledonia’s administrative congress in 2011 addressing legal issues of international regulations, customs, logistics of air transportation, and surgery. Ethical aspects were also discussed in the Kanak Customary Senate, which is independent from Congress and Government, and addresses matters related to Kanak identity, ensuring that the program was consistent with local values and beliefs.

An HLA tissue typing laboratory was established at the CHT and accredited according to the standards of Asia-Pacific Histocompatibility and Immunogenetics Association. The Australian New South Wales state government approved the program. The intensive care unit began identifying brain dead patients and potential donors through the European Donor Action Program. Medical and paramedical hospital staff were trained in organ retrieval. In addition, a coordination committee was founded. New Caledonia’s government authorized the CHT to undertake kidney retrieval activities for therapeutic purposes on November 28, 2012.

When a potential brain-dead organ donor is identified in Noumea, the Australian retrieval team is contacted; once brain death is confirmed and family consent is obtained, an Australian perfusionist, initially accompanied by a transplant/retrieval surgeon, is dispatched to Noumea. Potential recipients on the New Caledonian waiting list are screened based on criteria set by the French ABM. Cross-matches are performed locally. Both kidneys are retrieved and accompany the 2 identified waitlisted patients back to Sydney, where transplant surgeries are performed.

Both recipients remain in Sydney for approximately 2 months, as per standard posttransplant care, before returning home. The costs of the program are covered by CAFAT, New Caledonia’s Health System, at a rate determined by the New South Wales Department of Health for international visitors. It should be noted that transplantation delivers significant overall cost savings derived from reduced dialysis requirements.

CLINICAL OUTCOMES

We retrospectively analyzed program outcomes from November 2012 to April 2018 (with approval by New Caledonian ethics committee).

A total of 86 brain-dead donors have been identified. Of those, 15 became actual donors (17%), resulting into 30 kidney transplants. Family refusal was the leading cause for not proceeding. Main reasons were due to tribal customs and the perceived violation to the body’s integrity. Three of the 15 retrievals were performed by an Australian surgical team, 8 by the local Noumean team, and 4 procurements have been performed jointly. Median donor age was 47 years (interquartile range [IQR], 29–61 y); 21 of 30 recipients were male (70%, median age: 56 y; IQR, 48–62 y); and median follow-up time was 24 months (IQR, 12–42 mo). Patients taking part in this program were older than those transplanted in France (mean age, 56 y [48–62 y] vs 42 y [32–52 y], P < 0.0001). Seventy percent of recipients had preexisting HLA antibodies predominantly against class I, but none were donor specific.

All patients received an induction treatment with Basiliximab and methylprednisone and a maintenance immunosuppression consisting of tacrolimus, mycophenolate mofetil, and steroids. Eight patients (27%) had delayed graft function (DGF), requiring dialysis within the first postoperative week.5 The rate of DGF observed in this series of patients was higher than in France’s (19.8% in 20166) and Australia’s (24.6%7).

Recipients with DGF tended to be older, with a median age of 59 years (IQR, 53–63 y) versus 55 years old for those without DGF (IQR, 44–59, P = 0.336). Moreover, patients with DGF tended to have an older donor (median donor age, 71 y, IQR 53–73 vs 42 y, IQR 22–54 for patients without DGF, P = 0.036). Cold ischemia times (CITs) were comparable between groups, with a median CIT of 14.4 hours (IQR, 12.3–17.4 h) in the DGF group versus 13.3 hours (IQR, 11.8–17.2 h) for patients without DGF (P = 0.979).

The overall mean CIT was 14.8 ± 4.2 hours compared with a general CIT of 16.5 hours for kidney transplants in France.6 By 3 months, the median estimated glomerular filtration rate (GFR) for New Caledonian recipients was 40 mL/min/1.73 m2 modification of diet in renal disease (MDRD) (IQR, 31–53).

Eight patients (27%) experienced surgical complications, with hematomas and urine infections being the most common. Thus far, 16 patients (53%) have been seen for their follow-up at 24 months, with a median GFR of 45 mL/min/1.73 m2 (IQR, 31–63). One recipient died from invasive pulmonary aspergillosis. There were 6 episodes of acute rejection in 6 patients (20%), all T cell mediated. The median GFR at last follow-up of these recipients was 43 mL/min/1.73 m2 MDRD (IQR, 30–51). Five recipients (17%) developed de novo class-II donor specific antibodies (maximum fluorescence intensity > 500). Weight gain was a significant issue post transplant; 7 recipients gained ≥ 10 kg post transplant. Moving forward, immunosuppressive regimens of Steroid minimization may help alleviate this problem.

The mean length of stay in Australia was 2.3 months (2–2.7 mo), compared with 22.5 months (14.4–32.9 mo) with a maximum stay of 89 months for those transplanted in France due to pretransplant waiting times. Once recipients return to New Caledonia, posttransplant care is resumed by their local nephrologist; tacrolimus trough levels and graft biopsies are performed locally and sent to Royal Prince Alfred Hospital for reporting. Communication links are maintained between the 2 units posttransplantation by phone and email when required.

FUTURE CHALLENGES

Organ donation is an emerging concept for New Caledonians. Donation rates are well below those expected by the European Donor Action Program; the main reason is family refusal based on cultural grounds. Several media campaigns have been launched to inform the population about the high prevalence of ESKD in New Caledonia and raise awareness about organ donation. Promoting organ donation is key in advancing the local deceased donor program. In parallel, the live donor kidney transplant program continues, with 36 New Caledonians transplanted in Australia between 2012 and 2018. In circumstances where the live donor pairs are immunologically incompatible, the Australian Paired Kidney Exchange program8,9 is utilized.

CONCLUSIONS

We present a unique and successful transplant program in a remote geographic area, where locally retrieved deceased donor kidneys accompany 2 local patients with ESKD to Australia for transplantation.

The program has delivered excellent outcomes, improved access to kidney transplantation, and helped address inequities for patients without live-donors or for those who are unable to leave the country for prolonged periods. These transplants have been performed with significantly less professional, cultural, and social disruptions.

This novel program has successfully facilitated deceased donor kidney transplantation in New Caledonia through a collaborative, integrated international approach defining a new paradigm for transplantation for the people of New Caledonia and may thus serve as a template for other countries under comparable circumstances.

ACKNOWLEDGMENTS

The authors wish to acknowledge the legacy of Professor Josette Eris, a driving force in establishing this collaborative project and instrumental in building the relationship between our 2 centers. Her dedication, vision, and clinical expertise ensured this program’s success.

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