Evaluation of Pancreatic Re-transplantation Outcomes
Author Information1
Grace Sharma2, Sissy Kou3, Vinay Yallapragada4
1All authors are listed in alphabetical order.
2Thomas Jefferson High School for Science and Technology, VA, 3Cupertino High School, CA, 4Academies of Loudoun, VA
Background
In this literature review, we will cover details of prior research. This review includes studies published after 2012. There is extremely limited information available about the outcomes of pancreas retransplants. Most studies in this field are single-center reports with small datasets. This literature review can be divided into three main areas:
- Analysis of graft survival in different forms of pancreas transplants
- Analysis of patient survival in different forms of pancreas transplants
- Review of recommendations to consider pancreas retransplants for patients
Several studies have identified the graft survival rates of retransplant patients and compared them with graft survival rates for other pancreas transplant patients. In [7], authors compared the graft survival between 187 primary transplant and 26 retransplant patients, noting that graft survival rates were lower amongst retransplants than primary transplants. In 2018, Gasteiger et al. [4] concluded that graft survival in first-time retransplant patients was similar to graft survival amongst patients that received more than one retransplant. In [1], Hollinger determined that graft survival was similar amongst patients who received an early retransplant and a delayed retransplant. Most studies analyzing graft survival rates in pancreas retransplants are single-center reports studying less than 50 patients each. In 2015, Siskind et al. [6] reviewed more than a thousand retransplants in a larger database, UNOS; the authors determined that graft survival in retransplant patients was significantly lower than primary transplant patients.
Most studies determining graft survival rates of retransplant patients also studied patient survival rates. In [2], the authors conducted an in-depth analysis of retransplants done after 2003 and determined that there was no significant difference between the patient survival rates of primary transplant and retransplant patients. In [7], the authors concluded that patient survival was not different for primary transplant patients and retransplant patients. The analysis on the UNOS database revealed that patient survival was greater in the retransplant group than the primary transplant group [6].
Most work in this field has concluded by supporting pancreas retransplants as a viable option for patients. In [5], the authors state that retransplants are feasible and that it should be considered for diabetic patients who have lost their first pancreas. In [3], where the authors analyzed 18 retransplant patients, the study concluded by determining that retransplants are a safe and effective procedure. In [7], the authors had determined that retransplants had lower graft survival than primary transplants yet concluded that it can be offered to diabetic patients. However, in [6], the authors analyzed over 1,000 retransplants and concluded that retransplants should not be considered for all patients.
Materials and Methods
Data and Data Sources
A retrospective analysis was performed using the UNOS database between January 1, 2010 and June 30, 2022. The UNOS database collects and reports information on every US organ donor, recipient, and outcome. Pediatric patients, recipients of pediatric donors, and multiple-organ transplants were excluded. Subsequent analysis categorized patients based on the type of transplant received as well as their retransplant status. For the type of transplant, the analysis grouped patients who received first-time or retransplants. For retransplant status, the analysis grouped patients who received simultaneous pancreas-kidney, pancreas after kidney, or pancreas transplant only transplants. The final dataset contained the data of 19,659 transplant recipients. Of those, 18,531 (94.09%) received first-time transplants and 1,164 (5.91%) received retransplants. When examining the data by transplant type, the study grouped together patients who were recipients of both first-time transplants and re-transplants.
Outcome and Explanatory Variables
Transplant outcomes including graft failure and patient death were compared by the first-time transplant and retransplant patients. Other recipient characteristics used for analysis include age, days on waitlist, retransplant recipient, diabetes status, dialysis status, glomerular filtration rate (GFR), BMU, and calculated panel reactive antibody (cPRA) at the time of transplant. For donor characteristics, we queried age, sex, ethnicity, BMI, creatinine level, history of hypertension, and measures of organ quality including kidneys from donors with cardiac death (DCD) and expanded criteria donors (ECD). Additional transplant-related variables including HLA mismatch level as well as cold ischemic time (CIT) and organ sharing status (local, regional, national), were also included.
Statistical Analysis
The basic patient, donor, and transplant characteristics were compared between the two cohorts using ANOVA tests for continuous and Chi-square/Fisher’s exact tests for categorical variables, depending on the sample size and the distribution of the variables involved. Survival curves and the estimates for the outcomes were obtained using the Kaplan-Meier (KM) Product Limit method. In the survival analysis. In the survival analysis of transplant outcomes, graft failure (for graft survival) or patient death (for patient survival) were the end-points. Recipients who did not experience any of these end-points or whose health or graft/patient status was unknown were censored on the last follow-up or the last day of the study. For those outcome variables used in the KM survival analyses, corresponding multivariable Cox regression analyses were also performed to investigate the risk factors for respective outcomes after controlling for covariates. Donor, patient, and transplant characteristics were investigated as potential risk factors. Statistical significance was defined by p<0.05 in the analysis.
Results
Table 1 demonstrates significant variations in patient, donor, and transplant characteristics across recipients transplant type. Pancreas-only transplants (PTA) patients were more likely to be older (42.06 years, p<0.001), White (93.16%, p<0.001), wait the shortest on the waitlist (262.05, p<0.001), and have the highest BMI (25.59, p<0.001). Pancreas-after kidney (PAK) patients were more likely to be retransplant recipients (26.26%, p<0.001) and on dialysis (29.41%, p<0.001). Simultaneous Pancreas-Kidney (SPK) patients were more likely to be male (61.85%, p<0.001), African American (20.24%, p<0.001), have diabetes at the time of transplant (99.88%, p=0.017), and had the lowest cPRA of the three types of transplants (9.82, p<0.001).
Table 2 demonstrates variations in patient and transplant characteristics across recipients of first-time and retransplant patients. First-time transplant recipients were more likely to be male (59.87%, p<0.001), African American (17.61%, p<0.001), and be on dialysis at the time of transplant (72.63%, p<0.001). First-time transplant patients were more likely to undergo SPK transplants (79.87%, p<0.001) and waited fewer days on the waitlist (389.34 days, p<0.022). Retransplant patients were more likely to be older (42.65 years, p<0.001), White (86.08%, p<0.001), and have a higher GFR (16.04 60 mL/min/1.73 m2, p=0.012).
Table 1: Baseline data for recipients, donors, and transplant characteristics by transplant type
| Characteristics | PTA(n = 1,564) | PAK(n = 3,172) | SKP(n = 14,959) | p-value |
| Patient Characteristics | ||||
| Male, n (%) | 608 (38.87%) | 1817 (57.28%) | 9252 (61.85%) | <0.001 |
| Age, mean (SD) | 42.06 (10.125) | 42.44 (8.099) | 41.81 (8.750) | <0.001 |
| White, n (%) | 1457 (93.16%) | 2612 (86.35%) | 9664 (64.60%) | <0.001 |
| Black, n (%) | 50 (3.20%) | 283 (8.92%) | 3028 (20.24%) | <0.001 |
| Hispanic, n (%) | 43 (2.75%) | 235 (7.41%) | 1792 (11.98%) | <0.001 |
| Asian, n (%) | 7 (0.45%) | 18 (0.57%) | 301 (2.01%) | <0.001 |
| Other, n (%) | 7 (0.45%) | 24 (0.76%) | 174 (1.16%) | <0.001 |
| Wait time (in days), median (IQR) | 262.05 (399.36) | 351.85 (406.78) | 358.08 (398.57) | <0.001 |
| Retransplant, n (%) | 173.00 (11.06%) | 833.00 (26.26%) | 158 (1.06%) | <0.001 |
| Diabetes at the time of TX, n (%) | 1553 (99.55%) | 3154 (99.87%) | 14924 (99.88%) | 0.017 |
| BMI at the time of TX, mean (SD) | 25.59 (4.06) | 25.11 (3.92) | 25.37 (3.85) | <0.001 |
| Dialysis at the time of TX, n (%) | 5.00 (55.56%) | 5.00 (29.41%) | 10,843.00 (72.53%) | <0.001 |
| cPRA at the time of TX, mean (SD) | 18.60 (32.51) | 14.87 (28.19) | 9.82 (22.50) | <0.001 |
| GFR at the time of TX, mean (SD) | 23.05 (10.15) | 42.50 (36.06) | 14.15 (4.55) | 0.032 |
| Donor Characteristics | ||||
| Male, n (%) | 1,020.00 (65.22%) | 2,215.00 (69.83%) | 10,254.00 (68.55%) | 0.005 |
| Age, mean (SD) | 28.25 (9.17) | 27.88 (8.96) | 28.03 (8.65) | 0.077 |
| White, n (%) | 1,102.00 (70.46%) | 2,207.00 (69.58%) | 9,742.00 (65.12%) | <0.001 |
| African American, n (%) | 223.00 (14.26%) | 433.00 (13.65%) | 2,576.00 (17.22%) | <0.001 |
| Hispanic, n (%) | 202.00 (12.92%) | 463.00 (14.60%) | 2,213.00 (14.79%) | 0.135 |
| Asian, n (%) | 18.00 (1.15%) | 50.00 (1.58%) | 285.00 (1.91%) | 0.061 |
| Other, n (%) | 19.00 (1.21%) | 19.00 (0.60%) | 143.00 (0.96%) | 0.071 |
| Creatinine at the time of TX, mean (SD) | 1.21 (1.10) | 1.15 (0.95) | 1.01 (0.72) | <0.001 |
| Diabetes at the time of TX, n (%) | 8.00 (0.51%) | 5.00 (0.16%) | 29.00 (0.19%) | 0.046 |
| Hypertensive at the time of TX, n (%) | 139.00 (8.94%) | 212.00 (6.71%) | 897.00 (6.03%) | <0.001 |
| BMI at the time of TX, mean (sd) | 24.34 (3.72) | 24.37 (3.79) | 24.40 (3.82) | 0.909 |
| Donor after Cardiac Death, n (%) | 41.00 (2.62%) | 18.00 (0.57%) | 364.00 (2.43%) | <0.001 |
| Expanded Criteria Donor, n (%) | 7.00 (0.45%) | 14.00 (0.44%) | 47.00 (0.31%) | 0.417 |
| Transplant Characteristics | ||||
| HLA mismatch level, mean (SD) | 4.04 (1.44) | 4.21 (1.33) | 4.53 (1.21) | <0.001 |
| Locally shared, n (%) | 645.00 (41.24%) | 1,679.00 (52.93%) | 12,236.00 (81.80%) | <0.001 |
| Regionally shared, n (%) | 293.00 (18.73%) | 660.00 (20.81%) | 1,710.00 (11.43%) | <0.001 |
| Nationally shared, n (%) | 625.00 (39.96%) | 832.00 (26.23%) | 1,013.00 (6.77%) | <0.001 |
| First-time TX (n = 18531) | 1391 (88.94%) | 2339 (73.74%) | 14801 (98.94%) | |
| Retransplant (n = 1164) | 173 (11.06%) | 833 (26.26%) | 158 (1.06%) |
Graft Failure
Figure 1 compares the graft failure rates by transplant type. PTA patients had the highest graft failure rate while SPK patients had the lowest graft failure rate (p<0.001). Figure 2 compares the graft failure rates by retransplant status. Retransplant recipients had a significantly higher graft failure rate than first-time transplant patients (p<0.001). Figure 3 compares the graft failure rates by transplant type of retransplant patients. Patients who received PTA retransplants had the highest graft failure rate while SPK retransplant patients had the lowest graft failure rate of any transplant type. First-time transplant patients had a higher graft failure rate than any type of retransplant. Table 3 summarizes the results of COX regressions for transplant recipients and donors, showing risk factors correlated with graft failure adjusted for covariates. For transplant recipients, being Hispanic (HR=0.81, p<0.001) reduced the risk of graft failure by 19%. Being on dialysis (HR=1.201, p<0.001) or having a higher BMI (HR=1.025, p<0.001) increased the graft failure rate by 20.1% and 2.5% respectively. For pancreas donors, being another race not directly measured (HR=0.631, p=0.015) reduced the graft failure rate by 36.9%. Being hypertensive (HR=1.121, p=0.033), an expanded criteria donor (HR=1.448, p=0.04), African American (HR=1.254, p<0.001), or being older (HR=1.015, p<0.001) increased the graft failure rate by 12.1%, 44.8%, 25.4%, and 1.5% respectively. Being a recipient of a PTA transplant (HR=5.143, p<0.001), PAK transplant (HR=1.978, p=0.011), or retransplant (HR=1.655, p<0.001) increased the graft failure rate by 414.3%, 97.8%, and 65.5% respectively.
Figure 1: Graft Failure based on Transplant Type
Figure 2: Graft Failure based on Retransplant Status
Figure 3: Graft Failure based on Transplant Type of Retransplant Patients
Table 3: Graft failure Cox Regression results
| Variable | HR | P-Value | [95% | C.I.] |
| Patient Factors | ||||
| Hispanic Recipient | 0.81 | <0.001 | 0.737 | 0.891 |
| Dialysis at time of Tx | 1.201 | <0.001 | 1.131 | 1.275 |
| BMI at time of Tx | 1.025 | <0.001 | 1.018 | 1.032 |
| Donor Factors | ||||
| Donor Age | 1.015 | <0.001 | 1.012 | 1.018 |
| African American Donor | 1.254 | <0.001 | 1.169 | 1.344 |
| Other Race Donor | 0.631 | 0.015 | 0.4353 | 0.9157 |
| Hypertensive Donor at time of Tx | 1.121 | 0.033 | 1.009 | 1.244 |
| Expanded Criteria Donor (ECD) | 1.448 | 0.04 | 1.018 | 2.06 |
| Transplant Type | ||||
| Pancreas Transplant Alone (PTA)1 | 5.143 | <0.001 | 2.57 | 10.29 |
| Pancreas After Kidney (PAK)1 | 1.978 | 0.011 | 1.165 | 3.357 |
| Retransplant2 | 1.655 | <0.001 | 1.345 | 2.036 |
1The reference group is recipients of SKP transplants.
2The reference group is first-time transplant recipients.
Patient Mortality
Figure 4 compares the patient mortality rates by transplant type. PAK patients had the highest patient mortality rate while SPK and PTA patients had similar patient mortality rates for the duration of follow-up (p<0.001). Figure 5 compares the patient mortality rates by retransplant status. Retransplant patients had a higher patient mortality rate than first-time transplant patients (p<0.001). Figure 6 compares the patient mortality rates by transplant type of retransplant patients. Patients who received SPK retransplants had the highest patient mortality rate while PTA retransplant patients had the lowest patient mortality rate. First-time transplant patients had a higher patient mortality rate than PTA retransplant patients for the duration of follow-up. Table 4 summarizes the results of the COX regressions for transplant recipients and donors, showing risk factors correlated with graft failure adjusted for covariates. For transplant recipients, being older (HR=1.024, p<0.001) or being on dialysis (HR=1.347, p<0.001) increases the patient mortality rate by 2.4% and 34.7% respectively. For transplant recipients, being older (HR=1.011, p<0.001), African American (HR=1.29, p<0.001), hypertensive (HR=1.171, p=0.005), or having a high HLA mismatch level (HR=1.036, p=0.003) increased the graft failure rate by 1.1%, 29%, 17.1%, and 3.6% respectively. Being a recipient of a PTA transplant (HR=6.614, p<0.001) or retransplant (HR=1.745, p<0.001) increased the graft failure rate by 561.4%, and 74.5% respectively.
Figure 4: Patient Mortality based on Transplant Type
Figure 5: Patient Mortality based on Retransplant Status
Figure 6: Patient Mortality based on Transplant Type in Retransplant Patients
Table 4: Patient mortality Cox Regression results (Please use the same variables as the graft failure regression)
| Variable | HR | P-Value | [95% | C.I.] |
| Patient Factors | ||||
| Recipient Age | 1.024 | <0.001 | 1.021 | 1.028 |
| Dialysis at time of Tx | 1.347 | <0.001 | 1.26 | 1.44 |
| Donor Factors | ||||
| Donor Age | 1.011 | <0.001 | 1.007 | 1.014 |
| African American Donor | 1.29 | <0.001 | 1.193 | 1.395 |
| Hypertensive Donor | 1.171 | 0.005 | 1.048 | 1.308 |
| HLA Mismatch Level | 1.036 | 0.003 | 1.012 | 1.061 |
| Transplant type | ||||
| Pancreas Transplant Alone (PTA)1 | 6.614 | <0.001 | 2.963 | 14.76 |
| Pancreas After Kidney (PAK)1 | 1.598 | 0.106 | 0.9047 | 2.822 |
| Retransplant2 | 1.745 | <0.001 | 1.391 | 2.189 |
1The reference group is recipients of SKP transplants.
2The reference group is first-time transplant recipients.
Conclusion
In conclusion, pancreas retransplants are associated with a higher risk of both graft failure and patient mortality. SPK transplants appear to have a lower risk of graft failure and patient mortality compared to other forms of pancreas transplant.