Australia And New Zealand Islet And Pancreas Transplant Registry Annual Report 2019-Pancreas Waiting List, Recipients, And Donors

WAITING LIST Overview of Waiting List Activity Definitions Patients join the waiting list on the date they are referred to the transplanting center; however, this may occur sometime before their kidneys fail. Patients are therefore classified as “under consideration” until they medically require a kidney-pancreas transplant. Once they require a kidney-pancreas transplant, they are classified as “active” on the list, while they remain medically fit. The “under consideration” classification also captures people recently referred to the transplant center, who are still undergoing assessment about their medical fitness for pancreas transplant. People referred to a transplanting center when they are already on dialysis, become “active” on the list as soon as they are accepted as medically fit. People referred to a transplanting center when their kidneys still function, become active once their kidney disease progresses to such a level that dialysis is planned in the near future. Once active on the waiting list, patients are transplanted in order of their waiting time by blood group. Patient Waiting List Flow The patient waiting list activity in the last 3 years for Australia (Westmead and Monash Units) and New Zealand are shown in Tables 1 and 2, respectively. In Australia, although the number of transplants has increased over the last 3 years, the number of patients on the active waiting list has continued to increase.TABLE 1.: Waiting list activity in Australia for the last 3 yTABLE 2.: Waiting list activity in New Zealand for the last 3 yDistribution of Active Patients by State Figure 1 and Table 3 show the state and country of residence for people active on the pancreas waiting list, by year and the pancreas transplanting center they were referred to (Australia only).TABLE 3.: Patient state of residence by Australian pancreas transplant unit for people active on the list, December 2018FIGURE 1.: Distribution of people active on the waiting list by state or country of residence, as of December 2018.New Referrals Received Overtime Table 4 shows the number of new referrals received by transplanting units in Australia and New Zealand (ANZ) overtime and by state of residence (for Australian units only).TABLE 4.: New referrals received overtime by pancreas transplant unit and state of residencePatient Characteristics for Those Active on the List in 2018 Figures 2 and 3 illustrate the distribution of other characteristics of those active on the waiting list in 2018, including the distribution of blood groups and patient ages.FIGURE 2.: Distribution of people active on the list by their blood group, in December 2018.FIGURE 3.: Distribution of people active on the list by their age, in December 2018.PANCREAS TRANSPLANT RECIPIENTS Pancreas Transplant Incidence A total of 866 solid organ pancreas transplants have been performed in ANZ from 1984 to 2018. Transplants have been performed in Westmead (533), Monash (263), Auckland (62), and Royal Adelaide (4). In 2018, the Royal Adelaide Hospital recommenced pancreas transplantation in South Australia and the Northern Territory using an anti-thymocyte globulin-based steroid-free protocol. There have also been multiorgan transplants, including pancreas at Royal Prince Alfred (1), Royal Melbourne Hospital (1), Queen Elizabeth Hospital (1), and Austin Hospital (1). Figure 4 shows pancreas transplants overtime. The number of transplants has substantially increased in last decade compared with previous years.1,2FIGURE 4.: Incidence of pancreas transplants overtime, 1984–2018.In 2018, 56 people received a pancreas transplant, by center this was Monash (20), Westmead (26), Royal Adelaide (4), and Auckland (6). The number of transplants in 2018 increased by 8% compared with 2017.2 Not all pancreas transplant operations are undertaken with the same organs. Simultaneous pancreas-kidney (SPK) transplant is the most common operation, representing 99% of all pancreas transplants in ANZ. From 56 transplants performed in 2018, 53 were SPK, 2 were pancreas after kidney (PAK), and 1 was pancreas transplant alone. PAK operations are done for type 1 diabetic people who either had a first kidney transplant without a pancreas (most commonly from a living donor relative) and subsequently opt for a pancreas, or for people who underwent an SPK and have good kidney transplant function, but had a pancreas transplant failure, so need a further pancreas transplant. Pancreas transplant alone is a less common operation and occurs very rarely. Its indications include management of patients with hypoglycemic unawareness or brittle diabetes that have failed best medical therapy. On rarer occasions, a multiorgan transplant is undertaken, which includes a pancreas transplant. There was 1 simultaneous pancreas, liver, and kidney transplant which was performed in 2005; 1 liver, pancreas, and intestine transplant in 2012; 1 liver and pancreas transplant in 2016; and 1 liver, kidney, pancreas, stomach, and intestine transplant in 2017. The distribution of operation types is shown in Figure 5, and the number of transplants by operation type is shown in Table 5.TABLE 5.: Pancreas transplant operations by center, overtimeFIGURE 5.: Pancreas transplants by type overtime, Australia and New Zealand.Patients Transplanted by State The states of origin of the people receiving pancreas transplants at each transplant unit in Australia overtime are shown in Table 6.TABLE 6.: Distribution of state of residence of people receiving pancreas transplants overtimeDemographics of New Pancreas Transplant Recipients The characteristics of pancreas transplant recipients in 2018 and in previous years are shown in Table 7. The primary diagnosis causing end-stage kidney disease of recipients during 2018 and historically was type I diabetes. The number of diabetic recipients with other causes of end-stage kidney failure was small. The number of type II diabetics accepted for pancreas transplantation was also small, and none were transplanted in 2018.TABLE 7.: Demographics and characteristics of pancreas transplant recipientsThe type of pancreas transplants and the types of donors for transplants performed in 2018 are presented in Table 8, stratified by country and sex.TABLE 8.: Transplant and donor types in 2018 by country and sexBalance of Donor and Recipient Characteristics in 2018 Cross tabulations of donor and recipient blood group and gender for people transplanted in 2018 are displayed in Tables 9 and 10. These distributions remain similar to previous years.1,2TABLE 9.: Cross tabulation of recipient and donor blood groups for 2018TABLE 10.: Cross tabulation of recipient and donor sex for 2018Patient Survival Patient survival is calculated from the date of transplantation until death. Patients still alive at the end of the follow-up period are censored. For people who had >1 transplant, their survival is calculated from the date of their first transplant. For these analyses, we had survival data for 846 patients, 20 of whom have received a second pancreas transplant, for a total of 866 pancreas transplants. Note that for the following survival plots, survival proportion on the y-axes does not always start at zero; this is to better demonstrate some observed differences. Patient survival by era of transplantation is shown in Figure 6. Survival has improved overtime (P < 0.001). Survival at 1 year for people transplanted before 2000 was 92.6%; in recent years, this has risen to 96.8%. Survival at 5 years was 88.5% for those transplanted before 2000, where for those transplanted in 2010 or later, 5-year survival was 93.7%.FIGURE 6.: Patient survival by era of transplantation.Patient survival by age at transplantation is shown in Figure 7. People who were older at the time of pancreas transplantation had poorer survival than those who were younger (P = 0.02). Survival at 1 year for recipients aged <35 years was 97.0% and for those aged 35–44 years was 96.5%, whereas for those aged 45–49 years was 94.8% and for those 50 years or older was 96.6%. Survival at 5 years for those aged <35 years was 92.5% and for those aged 35–44 years was 94.0%, whereas for those aged 45–49 years was 90.6% and for those 50 years or older was 92.9%. The greater survival for the 50 years and older group may be because these recipients are a more highly selected population.FIGURE 7.: Patient survival by age at transplantation.Pancreas Survival Pancreas transplant survival was calculated from the time of transplant until the time of permanent return to insulin therapy or pancreatectomy. We calculated both pancreas failure, including death with a functioning pancreas and pancreas failure censored at death with a functioning transplant. For pancreas transplant survival, we included all pancreas transplants undertaken, including those who had received a pancreas transplant twice (20 patients). At the time of this report, we had survival records for 866 pancreas transplants. Survival of pancreas transplants has changed overtime, as shown in Figure 8. Survival improved markedly overtime (P = 0.007). For those transplanted before 2000, 1-year pancreas transplant survival was 82.3% and 5-year survival 76.6%. For those transplanted in 2010 or later, 1-year survival was 93.5% and 5-year survival 88.0%.FIGURE 8.: Pancreas transplant survival overtime (censored for death).Pancreas transplant survival by donor body mass index (BMI) is presented in Figure 9. Most donors (64%) were either underweight or normal (BMI < 25). However, 31% were overweight (BMI 25–29) and 4% were obese (BMI 30+). While Figure 9 suggests separation of survival curves, there was no statistical association between donor BMI and pancreas survival (P = 0.6). Pancreas transplant survival at 1 year was 91.0% for transplants where the donor was underweight/normal BMI, 90.1% for transplants where the donor was overweight, and 86.1% where the donor was obese.FIGURE 9.: Pancreas transplant survival by donor BMI (censored at death). BMI, body mass index.Pancreas transplant survival by donor age is presented in Figure 10. The survival curves are poorer for donors aged 35–44 years compared with those 45 and older or younger donors (P = 0.03). We can only hypothesis that any difference may be due to donors over 45 being a more highly selected group, compared with the donors aged 35–44 years. Pancreas transplant survival at 1 year was 92.5% for transplants from donors aged 0–24 years, 90.1% for donors aged 25–34 years, 85.9% for donors aged 35–44 years, and 93.8% for donors aged 45+ years.FIGURE 10.: Pancreas transplant survival, censored for death with function, by donor age (censored at death).Pancreas graft survival at 1 and 5 years post transplant, censored at death and stratified by country and era of transplantation is presented in Table 11.TABLE 11.: People alive with a functioning pancreas transplant in Australia and New Zealand by y and residence, at y’s endPrevalence of Functioning Pancreas Transplants We calculated the point prevalence of people living in ANZ, who were alive with a functioning transplant on 31 December each year for the last 5 years (Table 12). The below numbers exclude people still alive, but whose pancreas transplant has failed. The number of functioning transplants is remaining steady overtime, possibly because recipients of early transplants are aging (with increased deaths and pancreas transplant failures), which is being offset by the increase in new transplants performed.TABLE 12.: People alive with a functioning pancreas transplant in Australia and New Zealand by y and residence, at y’s endKidney Transplant Survival Kidney transplant survival was calculated for those who received SPK transplants, from the time of transplantation until the time of return to dialysis. We calculated both kidney failure, including death with a functioning kidney and kidney failure censored at death with a functioning graft. For kidney transplant survival, we included only SPK transplants and excluded PAK transplant recipients. We had survival records for 835 SPK transplants. Kidney transplant survival improved overtime, with longer survival for those transplanted in more recent years (P < 0.001). For those transplanted before 2000, kidney transplant survival was 92.3% at 1 year and 88.6% at 5 years but was 98.2% at 1 year and 96.7% at 5 years for those transplanted in 2010 or later (Figure 11).FIGURE 11.: Kidney transplant survival for SPK transplant recipients overtime (censored at death). SPK, simultaneous pancreas-kidney.The era effect was even stronger when considering kidney failure, including death with kidney function (P < 0.001). For those transplanted before 2000, survival was 87.8% at 1 year and 81.0% at 5 years but was 95.7% at 1 year and 92.3% at 5 years for those transplanted in 2010 or later (Figure 12).FIGURE 12.: Kidney transplant survival for SPK transplant recipients overtime (including death as a kidney transplant failure). SPK, simultaneous pancreas-kidney.Pancreas Transplant Operative Data Characteristics of the pancreas transplant operations for 2018, previous years, and overall are shown in Table 13.TABLE 13.: Descriptive characteristics of pancreas transplant operationsSurgical Technique Exocrine drainage of the pancreas transplant has changed overtime. Enteric drainage of the pancreas was first used in ANZ during 2001. Figure 13 illustrates the number of transplants by pancreas duct management. Since 2001, most pancreas transplants have used enteric drainage of the pancreas duct.FIGURE 13.: Change in management of exocrine drainage of the pancreas overtime.The cytomegalovirus and Epstein-Barr virus matching of donor-recipient pairs are shown in Table 14.TABLE 14.: Infectious disease serology cross tabulation of donor-recipient pairsPANCREAS DONORS This section gives an overview of donors in 2018 and overtime. Donor eligibility criteria guidelines are available in the Transplantation Society of Australia and New Zealand consensus statement http://www.tsanz.com.au/organallocationprotocols/ but briefly require donors to be over 25 kg, and up to the age of 45 years, without known diabetes mellitus or pancreatic trauma, or history of alcoholism or pancreatic trauma. Donation after circulatory death may be considered up to the age of 35 years. As these are guidelines, there may be occasions when there is minor deviation from these advised criteria. Donor BMI is perceived as impacting recipient outcomes.3 Obese donors are more likely to have fatty pancreas, which results in more difficult surgery and increased postoperative complications and suboptimal insulin secretion. Alcohol consumption is defined by a history of consumption of >40 g/day. Table 15 describes pancreas donor characteristics in ANZ to date.TABLE 15.: Demographics and characteristics of pancreas transplant donorsPancreas Donor Characteristics The distribution of donor states of origin is shown in Table 16.TABLE 16.: Distribution of state of residence of pancreas donors in Australia overtime, by national pancreas transplant unitDonor and Recipient State/Territory Table 17 shows the distribution of donor organs according to state of origin, cross tabulated with the state of origin of the recipients who received those organs, for 2018, and from inception of the pancreas program. Note, these tables include Australian donors and recipients only.TABLE 17.: Number of pancreas transplants by donor and recipient state of residence in Australia for 2018 and all yACKNOWLEDGMENTS We would like to acknowledge the contributions of all Australia and New Zealand pancreas transplant collaborators: Dr Helen Pilmore, Prof Stephen Munn, Prof Peter Kerr, Prof John Kanellis, A/Prof Bill Mulley, Mr Alan Saunder, Mr Roger Bell, Mr Ming Yii, Miss Nancy Suh, Mr Stephen Thwaites, Mr Michael Wu, Ms Tia Mark, Prof Henry Pleass, Prof Philip O’Connell, Prof Jeremy Chapman, Dr Brian Nankivell, Prof Angela Webster, A/Prof Germaine Wong, Dr Natasha Rogers, Dr Brendan Ryan, Dr Lawrence Yuen, Prof Richard Allen, Dr Jane Holmes-Walker, Ms Kathy Kable, Mr Paul Robertson, Prof Wayne Hawthorne, Mr Abhijit Patekar, Prof Graeme Russ, Prof Toby Coates, Dr Shantanu Bhattacharjya, Dr Christin Russell, Dr Anthony Santosh Olakkengil, Dr Phillip Clayton, Prof Randall Faull, Dr Robert Carroll, and Ms Danielle Stephenson.