1 INTRODUCTION

The effect of the COVID-19 pandemic loomed large in 2020 and continued through 2021 in all areas of organ transplantation. The effect on pancreas transplantation, especially solitary pancreas transplants, was significant, with fewer transplants being performed and a sharp decrease in transplant rates in 2020. While most organs recovered their numbers to prepandemic levels in 2021, pancreas transplant numbers, including transplant rates, have not recovered to 2019 levels. In fact, the transplant rates for patients with type 1 diabetes decreased sharply in 2021. The overall numbers remained steady in 2021 due to an increase in transplants in patients with type 2 diabetes, with 26% of all transplants in 2021 in these patients. The goals of transplant and outcomes in patients with type 2 diabetes may not be identical to those in patients with type 1 diabetes, and these need to be better defined going forward as the proportion of patients with type 2 diabetes on the pancreas waiting list continues to increase.

One-year pancreas graft outcomes continue to be reported, as a result of a uniform definition of graft failure having been adopted in 2018. However, the rate of missingness for insulin dose and weight of recipient is a major issue, because one of the criteria for graft failure is a return to an insulin dose of 0.5 units/kg/day or greater. This will need to be addressed for more comprehensive reporting of graft failure in future iterations of this report.

A major accomplishment of the Scientific Registry of Transplant Recipients (SRTR) in 2021-2022 was the development of the new organ allocation simulator (OASIM). The simulated allocation modeling (SAM) software dated back about 20 years and was facing maintenance and operational challenges; therefore, the Health Resources and Services Administration (HRSA) tasked SRTR with creating an updated organ allocation simulator. OASIM was designed with the goals of supporting the same functionality as the SAM software: an event-based microsimulation that can run on a desktop computer, supporting a wider range of policy types and modeling approaches, and, most important, unifying the codebase for simulating all organ allocation policies.

The Organ Procurement and Transplantation Network (OPTN) Kidney and Pancreas Continuous Distribution Workgroup submitted a simulation request to SRTR in April 2022 to model four continuous allocation scenarios with varying priorities and compare them to existing policy. The Workgroup identified attributes under the following goals for each of these scenarios for pancreas/kidney-pancreas/pancreas islet allocation: candidate biology, patient access, and placement efficiency. Each goal contained specific attributes that were differentially weighted based on the scenario. The simulation results were presented at the fall 2022 meeting of the OPTN Pancreas Transplantation Committee. Additionally, the OPTN Kidney Transplantation Committee and Pancreas Committee are in collaboration with the Massachusetts Institute of Technology (MIT) to perform a mathematical optimization analysis to help the Committees determine a range of acceptable policy options. MIT is augmenting SRTR’s SAM with machine learning to quickly and accurately predict outcomes by identifying policies (attribute weights) that achieve any set of prespecified outcomes in near real-time. MIT did similar work for the lung continuous distribution project and helped inform the OPTN Lung Transplantation Committee’s selection of weights for various attributes. The Workgroup is expected to submit a second modeling request with further refinements in the near future.

The American Society of Transplantation’s Kidney Pancreas Community of Practice (KP COP) performed a recent national survey showing that the number of pancreas transplants performed at the local and national levels are not keeping pace with the needs of patients with diabetes who could benefit from these procedures. The KP COP went on to organize a national workshop with the following objectives: improving the candidate referral process before pancreas transplant and candidate selection, identifying best practice guidelines for maximizing donor utilization/organ procurement organization awareness, expanding excellence in patient outcomes and program performance, and identifying educational and research improvements in pancreas transplant, and competing therapies. The formal recommendations of this workshop, if implemented over time, would likely spur growth in pancreas transplantation. In addition, the International Pancreas and Islet Transplant Association is in the process of constituting a pancreas interest group with similar objectives of optimizing growth in pancreas transplantation.

2 WAITING LIST

The number of adult candidates added to the waiting list increased sharply for simultaneous pancreas-kidney transplant (SPK) in 2021 to 1,487 from 1,307 the previous year (Figure PA 1). This is the highest number since 2010. Prevalent adult listings also increased in SPK (3,207 in 2021 vs 3,044 in 2020) and pancreas transplant alone (PTA; 544 in 2021 vs 508 in 2020) (Figure PA 2), whereas pancreas-after-kidney transplant (PAK) was largely unchanged.

The age distribution of candidates on the waiting list shows an increase in two older age groups (35-44 and 55 years or older) and a corresponding decrease in the younger age group (18-34 years) (Figure PA 3). This is likely due to higher proportion of patients with type 2 diabetes being listed over the past few years.

Male to female ratio on the waiting list has remained fairly consistent over the past decade at 55:45 (Figure PA 4). The proportion of White candidates continues to decline, with a corresponding increase in candidates from racial and ethnic minority groups. White candidates constituted 52.3% of the list in 2021, a decrease of 23.8% from 2010 (68.6%). Listing of Black candidates increased by 54.3% (from 17.2% in 2010 to 26.5% in 2021); Hispanic candidates, by 38.3% (from 11% in 2010 to 15.3% in 2021); and Asian candidates, by 150.2% (1.7% in 2010 to 4.2% in 2021) (Figure PA 5).

Most of the waitlist demographic changes can be largely attributed to an increase in candidates with type 2 diabetes on the waiting list (22.9% in 2021 vs 7.8% in 2010) (Figure PA 6). The proportion of candidates with type 1 diabetes decreased to 70.5% in 2021 versus 83.2% in 2010. As would be expected, the proportion of candidates with higher body mass index (BMI) increased. Candidates with BMI of 30-<35 kg/m² showed the highest increase (14.5% in 2010 to 20.1% in 2021), whereas those with BMI 18.5-<25 kg/m² showed the largest decrease (41.7% in 2010 to 33.8% in 2021) (Figure PA 8). Of note, 3.8% of the candidates have a BMI of 35 kg/m² or greater, and this number has remained steady over the years.

The distribution of candidates by waiting time shows that 50.5% of candidates were within 1 year of listing (a slight increase) and 28.4% of candidates have been on the waiting list for 2 years or longer (a slight decrease) (Figure PA 7). The distribution of candidates by blood type was largely unchanged in 2021: O, 48.1%; A, 33.1%; B, 15.4%; and AB, 3.5% (Figure PA 9).

With regard to transplant type, SPK candidates continued to predominate (77.3% in 2021 vs 67.5% in 2010) (Figure PA 10), whereas PAK (9.6% in 2021 vs 18.5% in 2010) and PTA (13.1% in 2021 vs 14% in 2010) have seen a significant decrease. Retransplant candidates as a proportion of the waiting list continued to decrease to 7.9% in 2021 from 16.1% in 2010 (Figure PA 11).

Pancreas transplant rates, which decreased sharply in 2020 to 40.2 per 100 patient-years, did not increase in 2021 (40.2 again) (Figure PA 12). Looking at the distribution by diagnosis, transplant rates decreased for candidates with type 1 diabetes (36.9 per 100 patient-years in 2021 vs 38.2 per 100 patient-years in 2020) but increased in candidates with type 2 diabetes (52.1 per 100 patient-years in 2021 vs 49.8 per 100 patient-years in 2020) (Figure PA 13). Transplant rates by blood type showed no change from 2020 to 2021 in blood types O and A; there was a slight decrease in type B and a larger decrease in type AB, but this is presumably due to a small number of AB transplants performed (Figure PA 14). Transplant rates by type of transplant (SPK, PAK, and PTA) also did not change significantly from 2020 to 2021 (48.3, 11.9, and 23.7 per 100 patient-years, respectively) (Figure PA 15).

Three-year outcomes for patients added to the waiting list during 2016-2018 showed 61.7% of SPK candidates, 38.1% of PAK candidates, and 49.2% of PTA candidates underwent transplant (Figures PA 16, 17, and 18). Patients who died or were removed from the list accounted for 22% of SPK candidates, 36.1% of PAK candidates, and 32.5% of PTA candidates. Patients still waiting at the end of 3 years accounted for 11% of SPKs, 25.9% of PAKs, and 18.3% of PTAs. Overall mortality on the waiting list amounted to 5.2 per 100 patient-years in 2021, a decrease from 2020, but has held steady at 4-6 per 100 patient-years over the past decade (Figure PA 19). However, when broken down by age groups, there was a decrease in mortality on the waiting list in two of the older age groups (35-44 and 45-54 years) in 2021 and a simultaneous increase in the younger age group (18-34 years) compared with 2020 (Figure PA 20). When broken down by race and ethnicity, there were no major differences in the change in mortality rate on the waiting list year over year from 2020 to 2021 (Figure PA 21).

Mortality on the waiting list decreased slightly for both men and women in 2021 versus 2020, with men having a lower mortality than women (Figure PA 22). By transplant type, SPKs had the highest mortality rate on the waiting list in 2021 at 6.2 per 100 patient-years (vs 2.1 for PAKs and 2.7 for PTAs) (Figure PA 23).

Table 1 lists characteristics of waitlisted candidates by transplant type. Of note, most SPK (61.7%) and PAK (61.9%) candidates lived within 50 miles of the transplant center. PTA candidates tended to come from farther away, with 48.9% from within 50 miles and 15.2% from 250 miles away or farther from the transplant center. Metropolitan areas account for most candidates across all groups (83.2%). There are geographical variations by donation service area in the pretransplant mortality rates, but the significance of this is unclear (Figure PA 24).

Deaths within 6 months of removal from the waiting list increased for the second straight year, to 8.4% in 2021 from 6.6% in 2020 and 5.7% in 2019 (Figure PA 25). Reasons for this increase are not absolutely clear. The increase was most pronounced for those aged 45-54 years, and values actually decreased slightly for those aged 35-44 years and 55 years or older (Figure PA 26). The increase in death after removal was pronounced in SPKs, with PAKs and PTAs seeing a decrease in deaths (Figure PA 27).

3 DONATIONS

The number of deceased pancreas donors increased to 1,307 in 2021 compared with 1,256 in 2020 (Figure PA 28). The increase was across all age groups (Figure PA 29). The distribution of donors across age groups remained largely unchanged, with the younger age group (18-29 years) accounting for most donors (51%) (Figure PA 30). Also notable is that 19% of donors were younger than 18 years and 6.1% were aged 40 years or older. Sex distribution has been relatively unchanged over the past decade, with a male to female ratio of 69.5:30.5 in 2021 (Figure PA 31). Race distribution of donors reveals that most donors are still White (60.7% in 2021), although this proportion has been gradually decreasing over the past decade (64.9% in 2010). The proportion of Black donors decreased slightly (18.6% in 2021 vs 20.4% in 2020), while that of Asian donors increased (2.2% in 2021 vs 1.5% in 2020) (Figure PA 32). With regard to BMI, there has been a trend towards an increasing proportion of donors in the 18.5-25 kg/m² category (55.7% in 2021 compared with 51.6% in 2018) (Figure PA 33). Donors with BMI >30 kg/m² is at the lowest level in a decade (7% in 2021). Cause of death among deceased pancreas donors was largely unchanged year over year from 2020 to 2021; however, there has been a trend of decreasing proportion of head trauma compared with anoxia over the past decade, presumably from the opioid epidemic, but this curve seems to be flattening out since 2020 (onset of COVID-19 pandemic) (Figure PA 34).

Because the number of donors in 2021 increased and the number of transplants remained unchanged, the nonuse rate for pancreas (pancreata recovered for transplant but not transplanted) expectedly increased (26.2% in 2021 vs 23.4% in 2020) (Figure PA 35). Compared with other organs, pancreas has a high nonuse rate, and this is due to a combination of factors including demand versus supply, adequate expertise of surgical teams, and cold ischemia time. Nonuse rates across age groups up to 39 years were between 23.4% and 29.8%, then increase in the 40- to 54-year age group to 42.9% (Figure PA 36). By sex, nonuse rates are virtually identical between male and female donors (Figure PA 37). Nonuse rates by race and ethnicity reveal a sharp decrease in rates of nonuse for Asian donors; however, this is an exaggerated effect due to small numbers (Figure PA 38). Nonuse rates by BMI show no major differences between BMI groups, except in groups with BMI of 35 kg/m² or greater where there were sharp changes, due to low numbers in those groups (Figure PA 39). Nonuse rates by US Public Health Service donor risk factors for blood-borne disease transmission showed little difference between groups (Figure PA 40).

4 TRANSPLANTS

The number of overall pancreas transplants has remained stable in 2021 compared with 2020 but has not recovered from prepandemic numbers—and approximates the nadir seen in 2015 (Figure PA 41). The recovery for pancreas transplants is lagging behind that of other organs, which may in part be related to the large numbers of programs that put pancreas transplants on hold related to the increased resources required. Of note, the number of SPKs is higher than prepandemic values, particularly from the low in 2014, but PAK and PTA numbers have continued to decrease over the past decade (Figure PA 42). It will be important to see whether the numbers of PAK and PTA rebound with reduction in the incidence of COVID-19.

There have been some notable changes in the age distribution of pancreas transplant recipients, with a substantial decrease in the number of pancreas transplants performed in recipients aged 18-34 years and a substantial increase in those aged 55 years or older from 11.7% of recipients in 2020 to 13.5% of recipients in 2021 (Figure PA 43). The shift to older age groups correlates with the notable increases in the number of pancreas transplants being performed for patients with type 2 diabetes (Figure PA 46). Similarly, the relative decrease in the number of pancreas transplants performed in the White population compared with the relative increase in the number of pancreas transplants performed in Black, Hispanic, and Asian recipients (Figure PA 45 and Table PA 10) correlates with the increased numbers of pancreas transplants performed for type 2 diabetes. The percentage of pancreas transplants performed for type 2 diabetes increased from 21.3% to 25.9% from 2020 to 2021 (Figure PA 46). Clearly, the demographic data of pancreas transplantation are being affected by the increasing numbers of transplants performed in people with type 2 diabetes.

Immunosuppressive regimens for pancreas transplants have remained stable for the past decade, reflecting the recognition that aggressive induction and maintenance regimens have been required for all categories of pancreas transplant to block the alloimmune and autoimmune responses that are necessary for successful transplant in people with type 1 diabetes. Induction with lymphodepleting regimens (Figure PA 47) and maintenance with tacrolimus and mycophenolate mofetil (Figure PA 48) are used in more than 90% of pancreas transplant recipients. Of note, steroids appear to be used in nearly 70% of regimens despite early hopes that steroids could be eliminated from the immunosuppressive regimens of people with diabetes. Indeed, nephrotoxic and beta-cell toxic calcineurin inhibitors and steroids continue to be used in the vast majority of pancreas transplant recipients.

The proportion of pancreas transplants performed at medium-volume centers (11-24 transplants per year) increased sharply to 48.3% in 2021 from 35.1% in 2020, with a corresponding decrease in transplants at large-volume centers (25 or more transplants per year) to 15.9% in 2021 from 25.7% in 2020 (Figure PA 53). Recovery from the COVID-19 pandemic will likely further affect shifts in the center volumes of the resource-intense pancreas transplants.

5 OUTCOMES

This 2021 Annual Data Report marks the second year that the new definition of pancreas graft failure has been in effect. Prior to 2020, SRTR did not report pancreas graft survival rates, because the accuracy of these data was compromised by the lack of consistent definitions of graft failure. Although patient survival and kidney allograft survival had precise definitions and consequently the reporting was accurate, there was considerable variation in each center’s definition of pancreas graft success. Some programs considered insulin independence to be the criterion for defining pancreas allograft success, while others defined it by C-peptide production. Some programs considered any use of oral hypoglycemic agents or insulin as the definition of graft failure. The current uniform definition for pancreas graft failure includes any of the following: 1) a recipient’s transplanted pancreas is removed; 2) a recipient reregisters for a pancreas transplant; 3) a recipient registers for an islet transplant after undergoing a pancreas transplant; 4) a recipient dies; or 5) a recipient’s total insulin use is greater than or equal to 0.5 units/kg/day for 90 consecutive days (OPTN Policy 1.2: definitions). This last definition may be problematic if the recipient’s starting insulin dose was less than 0.5 units/kg/day.

Using the new definition, the incidence of pancreas graft failure at 90 days posttransplant had remarkable increases for PAK and PTA, but not SPK, in 2021. The incidence of pancreas graft failure for PAK increased from 4.2% to 9.5% and that for PTA increased from 8.9% to 17.8% from 2020 to 2021 (Figure PA 54). Because these graft losses occurred early, they likely represent early technical losses.

There were notable increases in pancreas graft failure for all three categories of pancreas transplants within the first year of transplant. First-year pancreas graft failures increased between 2019 and 2020 from 6.8% to 14.6% for PAK, 10.3% to 15.6% for PTA, and from 7.2% to 10.5% for SPK (Figure PA 55). This is the first year this 1-year pancreas graft survival is available using the uniform definition of graft failure, and the higher rates of graft failure may reflect the stricter definition of graft failure.

Data for kidney allograft failure after SPK have been based on uniform definitions (ie, return to dialysis), unlike the previous variability in reporting pancreas allograft outcomes. Unadjusted outcomes for kidney allografts after SPK remained excellent, with 1-, 5-, and 10-year all-cause kidney failure at 5.7%, 16.4%, and 32.3%, respectively (Figure PA 56). The excellent long-term outcomes associated with SPK can be partly attributed to the lower kidney donor profile index (KDPI) for kidneys associated with SPK. However, the long-term kidney allograft success rates after PAK with a deceased donor kidney are also excellent, with 1-, 5-, and 10-year all-cause kidney graft failure rates of 6.3%, 14.7%, and 31.0%, respectively (Figure PA 58). The 10-year death-censored kidney graft failure among adult PAK transplant recipients with a decreased donor kidney had a marked decrease to 11.5% (Figure PA 59). The excellent long-term outcomes could be attributed to minimization of recurrent diabetic nephropathy in the presence of a functioning pancreas transplant. The 10-year death-censored kidney graft failure for SPK was 18.3% for the most recent cohort available for analysis (transplant in 2011-2012) (Figure PA 57), again reflecting the excellent KDPI of the kidneys used in SPK combined with the prevention of recurrent diabetic nephropathy with a normalized hemoglobin A1C. Finally, for PAK with a living donor kidney, the 10-year death-censored kidney graft failure was 14.3% (Figure PA 61). These low kidney graft failure rates highlight the high-quality kidneys of the deceased donors used in SPK and PAK and those of living donors in PAK.

Rejection rates after pancreas transplant have been consistently low for the past 5 years, with a rejection rate of 12.3% in the first year for recipients aged 18-34 years and 9.6% for recipients aged 35-64 years (Figure PA 63). The low rejection rates reflect a consistent and aggressive immunosuppressive approach used by more than 90% of transplant centers (Figures PA 47 and 48). Fortunately, there has not been an increase in the cumulative incidence of posttransplant lymphoproliferative disease (PTLD), which has remained consistent over the past 5 years. The highest cumulative incidence of PTLD was observed in Epstein-Barr virus (EBV)–negative PTA recipients (5.8%) compared with EBV-positive PTA recipients (1.6%) (Figure PA 66). The 5-year cumulative incidences of PTLD in EBV-negative PAK and SPK recipients were lower, at 2.2% (Figure PA 65) and 2.3% (Figure PA 67), respectively. The higher incidence of PTLD observed in EBV-negative PTA recipients may reflect the more aggressive immunosuppressive regimens that were historically used to manage PTA.

The safety of pancreas transplants is reflected in the ongoing low patient mortality rates for all categories of pancreas transplants at 1 year: 2.8%, 0%, and 3.6% for PAK, PTA, and SPK, respectively (Figure PA 68). Ten-year mortality rates in 2011-2012 transplant recipients were 20.1%, 18.5%, and 23.2%, for PAK, PTA, and SPK, respectively, likely reflecting the cardiovascular comorbidities in the population (Figure PA 70). Five-year survival rates for pancreas recipients were 92.2% and 89.1% for type 1 and type 2 diabetes, respectively (Figure PA 72). As more SPKs are performed for type 2 diabetes, seeing whether pancreas outcomes (using uniform definition of graft failure initiated in 2018) are comparable in both graft outcomes and survival will be of continued importance. Finally, the comparable 5-year patient survival among adult deceased donor pancreas transplant recipients in metropolitan versus non-metropolitan settings (92% in both settings) suggests that access to appropriate follow-up is not limited for recipients living in nonurban settings (Figure PA 73).

This publication was produced for the U.S. Department of Health and Human Services (HHS), Health Resources and Services Administration (HRSA), by Hennepin Healthcare Research Institute (HHRI) and the United Network for Organ Sharing (UNOS) under contracts HHSH75R60220C00011 and HHSH250201900001C, respectively.

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Suggested Citations:
Full citation: Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2021 Annual Data Report. U.S. Department of Health and Human Services, Health Resources and Services Administration; 2023. Accessed [insert date]. http://srtr.transplant.hrsa.gov/annual_reports/Default.aspx
Abbreviated citation: OPTN/SRTR 2021 Annual Data Report. HHS/HRSA; 2023. Accessed [insert date]. http://srtr.transplant.hrsa.gov/annual_reports/Default.aspx

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