Pancreas Transplant Recipients Research Articles

Pancreas Transplant Outcomes in Patients with Human Immunodeficiency Virus Infection

There is limited information on access and outcomes of patients living with HIV(PLWH) who have undergone pancreas transplantation. We conducted a retrospective cohort study analyzing data from the United Network for Organ Sharing from 7/1/2001-6/30/2021. Recipients of pancreas transplant were stratified by HIV serostatus. Graft and patient survival were analyzed using Kaplan-Meier product limit estimates. Multivariable Cox proportional hazard models were generated to identify factors associated with increased mortality or graft loss. Fifty PLWH and 16,380 patients without HIV underwent pancreas(with kidney) transplantation. PLWH were more often male(p<0.001), Black/African American(p=0.009), and on Medicare(p=0.004). There were no significant differences in waiting time(p=0.159) or proportion of patients treated for rejection within one year of transplant(p=0.189) between groups. There were no differences in pancreas graft survival(p=0.964) and overall patient survival(p=0.250) between the cohorts. Dialysis status was negatively associated with graft survival. Although PLWH were more likely to represent a historically marginalized population, their outcomes after pancreas transplant were similar to their HIV-negative counterparts.

Pregnancy Management and Outcomes in a Small Bowel, Pancreas, and Liver Transplant Recipient: A Case Report and Literature Review.

BACKGROUND Small bowel transplantation (SBT) is a rare but life-saving surgery. However, successful full-term pregnancies in individuals with SBT are exceedingly rare due to the nutritional and immunosuppression challenges this transplant poses for pregnancy. Therefore, clear guidelines for treating pregnant SBT recipients are unavailable. Here, we report the second case of a successful pregnancy in an individual with a triple organ transplant, including SBT, highlighting the need for careful immunosuppressive management and multidisciplinary care. CASE REPORT A 20-year-old woman in the third trimester of pregnancy with a history of small bowel, liver, and pancreas transplantation at age 1 year presented with elevated liver function test results. She had been taking tacrolimus, sirolimus, and prednisone before pregnancy, with no signs of organ rejection. While sirolimus and prednisone was discontinued upon conception, laboratory test results at presentation revealed low serum tacrolimus levels. The patient had an acute kidney injury and pulmonary edema during her hospitalization and received a diagnosis of preeclampsia. She underwent a successful cesarean delivery, due to labor induction complications; however, about 1 month after hospital discharge, the patient experienced elevated liver enzymes, which was treated with high-dose steroids and adjusted tacrolimus. Sirolimus was restarted, and the patient's liver enzymes have been normalized to date. CONCLUSIONS Comprehensive multidisciplinary care, as well as monitoring and optimizing immunosuppression, are essential for pregnant SBT recipients throughout the prenatal, perinatal, and postpartum periods to mitigate risks, prevent graft rejection, and ensure positive maternal and fetal health outcomes.

Abdominal Gynecologic Procedures in Pancreas Transplant Recipients.

With the growing population of pancreas transplant recipients followed long-term, some female recipients are going to require surgical intervention for gynecologic symptoms and pathologies. Currently, there is a lack of literature describing how to approach this population and whether pelvic gynecologic procedures (GYN) can be performed safely given the proximity of the pancreatic (and possibly renal) allograft. In this single-center retrospective analysis, all pancreas transplant recipients that subsequently underwent GYN were reviewed. Subjects were identified by cross-referencing all pancreas transplants performed between January 2003 and December 2022 for any subsequent GYN. Demographics at transplant and GYN, indications and procedure performed, operative time, presence and involvement of a transplant surgeon, complications length of stay, and readmissions were reviewed. Seventeen patients who underwent a total of 19 GYN after pancreas transplantation were identified. Operations performed included tubal ligation (n=2), total abdominal hysterectomy with (n=6) or without bilateral salpingectomy (n=2), oophorectomy versus cyst drainage (n=2), bilateral oophorectomy (n=1), and unilateral (n=4) versus bilateral (n=2) salpingectomy. Four were performed through an open laparotomy and 15 were performed laparoscopically. In 11 cases, a transplant surgeon was involved intra-operatively. Eight of the 17 patients developed post-operative complications including post-operative fevers, fluid overload, neutropenia, elevated creatinine (n=2), nephrolithiasis, urinary tract infection, and incisional hernia. Five required readmission. GYN can be performed safely following pancreas transplantation, but careful planning and the involvement of the transplant surgery team are advised.

Pretransplant Hypoalbuminemia Is Not Associated with Worse Outcomes among Simultaneous Pancreas and Kidney Transplant Recipients

Pretransplant Hypoalbuminemia Is Not Associated with Worse Outcomes among Simultaneous Pancreas and Kidney Transplant Recipients

Subclinical Pancreas Rejection on Protocol Biopsy Within the First Year of Simultaneous Pancreas Kidney Transplant.

This single-center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post-transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10%vs. 7%) and clinical rejection (21%vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24-24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection.

Expansion of the Pancreas Transplant Recipient Pool: Appropriate for Most or Are There Limits?

Expansion of the Pancreas Transplant Recipient Pool: Appropriate for Most or Are There Limits?

Cell-mediated Immunity to Guide Primary Prophylaxis for CMV Infection in Organ Transplant Recipients: A Multicenter Single-arm Prospective Study.

There are few interventional studies using CMV cell-mediated immunity (CMI) to guide antiviral prophylaxis. We assessed the Quantiferon-CMV (QTF-CMV) assay to guide CMV prophylaxis duration in high-risk organ transplant recipients. A single-arm, multicenter, prospective interventional study including high-risk kidney, pancreas, liver, and heart transplant recipients who were either donor CMV-seropositive, recipient-seronegative (D+/R-) or recipient-seropositive with antithymocyte globulin (R+/ATG) induction. CMI testing was performed using the QTF-CMV assay at months 3, 4, 5, and 6 posttransplant. Prophylaxis was discontinued for a positive CMI but continued for a negative result up to a maximum of 6 mo. The primary endpoint was CMV viremia ≥1000 IU/mL up to 1 y posttransplant. One hundred eight patients were included, comprising kidney (n = 89), kidney-pancreas (n = 7), liver (n = 10), and heart (n = 2) transplants. Eighty-nine patients (82.4%) completed the study protocol (n = 39 D+/R- and n = 50 R+/ATG). In the D+/R- group, only 1 of 39 patients (2.6%) had a positive QTF-CMV result. In the R+/ATG group, 33 of 50 patients (66%) had a positive QTF-CMV result before 6 mo, allowing for early discontinuation of prophylaxis (28 at month 3, 4 at month 4, and 1 at month 5). During the follow-up, CMV viremia ≥1000 IU/mL occurred in only 4 of 33 patients (12.1%) who discontinued prophylaxis early compared with 6 of 17 patients (35.3%) with negative QTF-CMV results and continued prophylaxis (hazard ratio 0.31; 95% confidence interval, 0.09-1.09; P = 0.07). No R+ patient developed CMV disease. QTF-CMV-guided prophylaxis appears useful in R+ patients who may benefit from a tailored duration of prophylaxis. This strategy does not appear to be useful in D+/R- patients.

Comparison of Post-Vaccination Response (Humoral and Cellular) to BNT162b2 in Clinical Cases, Kidney and Pancreas Transplant Recipient with Immunocompetent Subjects over Almost Two Years of Parallel Monitoring.

Vaccination is one of the most effective medical interventions to prevent infectious diseases. The introduction of vaccines against coronavirus acute respiratory syndrome 2 (SARS-CoV-2) was aimed at preventing severe illness and death due to coronavirus disease 2019 (COVID-19). Solid organ transplant recipients (SOTRs) are at high risk of infection with SARS-CoV-2 and serious effects associated with COVID-19, mainly due to the use of immunosuppressive therapies, which further cause suboptimal response to COVID-19 vaccination. We aimed to compare post-vaccination response to BNT162b2 in kidney-pancreas transplant recipient, specifically in immunocompetent individuals, over two years of simultaneous monitoring. To determine the humoral response, the levels of the IgG and IgA anti-S1 antibodies were measured. To assess the cellular response to SARS-CoV-2, the released IFN-γ-S1 was determinate. After primary vaccination, compared to immunocompetent subjects, SOTR showed lower seroconversion for both antibody classes. Only the additional dose produced antibodies at the level reached by the control group after the baseline vaccination. During the monitored period, SOTR did not achieve a positive cellular response in contrast to immunocompetent individuals, so in order to obtain longer protection, including immune memory, the adoption of booster doses of the vaccine should be considered.

The role of donor hypertension and angiotensin II in the occurrence of early pancreas allograft thrombosis.

About 10-20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis. We conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers. Pancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers. Donor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

Survival Advantages of Pancreas Transplantation

The field of transplantation has provided tremendous progress to diabetic patients. One way to objectify this development is to determine the survival advantage of transplantation in the 4 diabetic recipient categories: simultaneous pancreas and kidney transplantation (SPK), pancreas after kidney transplantation (PAK), pancreas transplantation alone (PTA), and kidney transplantation alone (KTA). Over a 21-year time period, from January 1, 2000, to May 31, 2021, the IPTR/UNOS collected information about listing and transplant outcome of diabetic patients. A total of 212,049 patient records were reviewed: 89,579 recipients who underwent pancreas and/or kidney transplantation and 122,470 patients who were placed on the waiting list and are still waiting or were removed from the waitlist due to deteriorating health or death. To determine the survival advantage of pancreas transplantation, patient survival on the waiting list versus after transplantation was defined as the primary outcome. Over the 21-year time period, pancreas and/or kidney transplantation in all 4 diabetic recipient categories saved a total of 273,843 life-years. On average, 11.7 life-years per patient were saved in the SPK category, 6.4 life-years in the PTA category, 6.3 life-years in the PAK category, and 6.6 life-years in the KTA category. The survival advantage of pancreas and/or kidney transplant recipients was highly significant compared to diabetic patients still waiting for transplantation. The survival advantage was higher for patients with type 1 vs. type 2 diabetes mellitus. The significant survival advantage of PTA recipients versus patients on the waiting list justifies the argument for pre-emptive pancreas transplantation, i.e., before the development of end-stage renal disease. Given the survival advantage as evidenced in 273,843 life-years saved, pancreas transplantation should be more widely applied, and pancreas donation encouraged.

O236: The Impact of HLA Matching on Pancreas and Simultaneous Pancreas-Kidney (SPK) Transplantation Outcomes

Abstract Background This study evaluates the controversial impact of human leukocyte antigen (HLA) matching on pancreas graft survival and acute rejection. Methods Utilizing a large-scale multi-center database (UNOS/OPTN), we identified 8,005 pancreas and 7,850 simultaneous pancreas-kidney (SPK) transplant patients. Patients were classified into HLA matched (0-3 mismatches) and mismatched (4-6 mismatches) groups. Subsequently, utilizing multivariate Cox analysis, we evaluated risk-adjusted outcomes, represented through Kaplan-Meier survival curves. We also examined differences in graft survival and acute rejection based on transplant type (SPK or pancreas alone) within the same HLA mismatch group. Findings There were no significant differences in pancreas graft survival or acute rejection observed between HLA matched and mismatched groups for both pancreas and SPK transplant recipients (P &amp;gt; 0.05). However, among HLA mismatched patients, pancreas patients exhibited a 629-day lower pancreas graft survival than SPK patients (3774 vs. 4403 days, P &amp;lt; 0.001) and had a higher likelihood of experiencing acute rejection post-transplant (P &amp;lt; 0.001). Similarly, within the HLA matched groups, pancreas patients showed lower graft survival compared to SPK patients (3774 vs. 4403 days, P &amp;lt; 0.001); however, their acute rejection rates did not significantly differ (P &amp;gt; 0.05). Interpretation Although HLA matching was not associated with improved pancreas graft survival or a reduction in acute rejection, the results suggest a potential protective effect of the kidney in SPK transplants against the consequences of HLA mismatching. This underscores the clinical significance of considering the kidney component in donor-recipient matching for pancreas transplantation.

Tixagevimab/cilgavimab for the prevention of COVID-19 in solid organ transplant recipients.

Tixagevimab/cilgavimab (tix/cil) received emergency use authorization in December 2021 for pre-exposure prophylaxis against COVID-19 in moderately to severely immunocompromised patients. Our study aimed to describe the incidence of COVID-19 infection and assess the immunologic risks associated with tix/cil in kidney, pancreas, liver, and heart transplant recipients. Retrospective chart review was completed to provide descriptive analysis. Outcomes data included COVID-19 infection, severity of COVID-19 infection, graft function, and rejection. Safety outcomes included cardiovascular (CV) and hypersensitivity events post tix/cil administration. A total of 410 transplant patients were included in the analysis: 20 heart, 92 liver, 243 kidney, 25 simultaneous pancreas/kidney, 23 simultaneous liver/kidney, and seven simultaneous heart/kidney. Twenty-seven (6.5%) patients tested positive for COVID-19 via PCR or antigen test post tix/cil. No apparent difference was observed in patients testing positive for COVID-19 by type of organ transplant (p=.122). Twenty-five of the 27 patients testing positive for COVID-19 reported symptomatic infection, only nine of whom were hospitalized. No patients were mechanically ventilated and no deaths due to COVID-19 occurred. No significant changes in graft function were observed. Clinically significant rejection was diagnosed and treated in four patients. COVID-19 breakthrough infection rates remained low in immunocompromised solid organ transplant recipients who received tix/cil. No significant immunologic risks were observed.

Tacrolimus's Time Below Therapeutic Range Is Associated With Acute Pancreatic Graft Rejection and the Development of De Novo Donor-specific Antibodies.

Tacrolimus is pivotal in pancreas transplants but poses challenges in maintaining optimal levels due to recipient differences. This study aimed to explore the utility of time spent below the therapeutic range and intrapatient variability in predicting rejection and de novo donor-specific antibody (dnDSA) development in pancreas graft recipients. This retrospective unicentric study included adult pancreas transplant recipients between January 2006 and July 2020. Recorded variables included demographics, immunosuppression details, HLA matching, biopsy results, dnDSA development, and clinical parameters. Statistical analysis included ROC curves, sensitivity, specificity, and predictive values. A total of 131 patients were included. Those with biopsy-proven acute rejection (BPAR, 12.2%) had more time (39.9% ± 24% vs. 25.72% ± 21.57%, p = 0.016) and tests (41.95% ± 13.57% vs. 29.96% ± 17.33%, p = 0.009) below therapeutic range. Specific cutoffs of 31.5% for time and 34% for tests below the therapeutic range showed a high negative predictive value for BPAR (93.98% and 93.1%, respectively). Similarly, patients with more than 34% of tests below the therapeutic range were associated with dnDSA appearance (38.9% vs. 9.4%, p = 0.012; OR 6.135, 1.346-27.78). In pancreas transplantation, maintaining optimal tacrolimus levels is crucial. Suboptimal test percentages below the therapeutic range prove valuable in identifying acute graft rejection risk.

Validation of the Back-table Graft Arterial Anastomosis between the Splenic Artery and Superior Mesenteric Artery: Arterial Complications after a 21-year Single-center Experience of Pancreas Transplantation.

To determine the role of the arterial splenomesenteric anastomosis (ASMA) vascular reconstruction technique in terms of arterial vascular complications in pancreas transplant (PT) recipients. The ASMA technique was first described in 1992 by Hospital Clínic Barcelona group. Regardless that the iliac Y-graft technique is the most frequently used worldwide, evidence of arterial complications and implications of using a different back-table reconstruction is conspicuously absent in the literature. Descriptive review of 407 PTs performed at a single center (1999-2019) by analyzing the type of arterial reconstruction technique, focusing on ASMA. The endpoints were the management of arterial complications and long-term patient and graft survival. ASMA was performed in 376 cases (92.4%) and a Y-graft in 31 cases (7.6%). A total of 34 arterial complications (8.3%) were diagnosed. In the ASMA group (n=30, 7.9%) they comprised: 15 acute thrombosis; 4 stenosis; 1 pseudoaneurysm and 10 diverse chronic arterial complications while in the Y-graft group (n=4, 12.9%) 3 acute thrombosis and 1 chronic artery-duodenal fistula occurred. Graft salvage was achieved in 16 patients (53.3%) from the ASMA group and in 2 (50%) from the Y-graft. After a median follow-up of 129.2 (IQR 25-75%, 77.2 -182) months the overall graft and patient survival for the whole cohort at 1, 5, and 10 years was 86.7%, 79.5%, 70.5%, and 98.5%, 95.3%, 92.5%, respectively. The ASMA proves to be a safe and more easily reproducible technique and should therefore be considered for first-line back-table reconstruction in the PT population.

Risk factors and outcomes of persistent post-transplant hypotension among simultaneous pancreas and kidney transplant recipients.

The risk factors and outcomes associated with post- transplant hypotension after simultaneous pancreas and kidney (SPK) Transplantation are poorly defined. SPK recipients at our center between 2010 and 2021 with functioning pancreas and kidney grafts for >6 months were included. Recipients were then divided into three groups based on active medications for the treatment of hypo-or hypertension at 6-months post-transplant: those with normal blood pressure (NBP) not requiring medication (NBP group), those on antihypertensive medications (HTN group), and those on medications for hypotension (fludrocortisone and/or midodrine) (Hypotensive group). A total of 306 recipients were included in the study: 54 (18%) in the NBP group, 215 (70%) in the HTN group, and 37 (12%) in the Hypotensive group. On multivariate analysis, the use of T-depleting induction (aHR=9.64, p=.0001, 95% Cl=3.12-29.75), pre-transplant use of hypotensive medications (aHR=4.53, p=.0003, 95% Cl=1.98-10.38), and longer duration of dialysis (aHR=1.02, p=.01, 95% Cl=1.00-1.04) were associated with an increased risk of post-transplant hypotension. Post-transplant hypotension was not associated with an increased risk of death-censored kidney or pancreatic allograft failure, or patient death. Hypotension was common even 6 months post-SPK transplantation. With appropriate management, hypotension was not associated with detrimental graft or patient outcomes.

Incidence, Risk Factors, and Outcomes of Post-Transplant Erythrocytosis Among Simultaneous Pancreas and Kidney Transplant Recipients

Incidence, Risk Factors, and Outcomes of Post-Transplant Erythrocytosis Among Simultaneous Pancreas and Kidney Transplant Recipients

Real-World Experience With CMV inSIGHT T Cell Immunity Testing in High-Risk Kidney and Pancreas Transplant Recipients.

Cytomegalovirus (CMV)-specific cell-mediated immunity is important for control of CMV after transplant. Assays exist to measure this, but their place in therapy is unclear, particularly in CMV high-risk recipients, without pretransplant exposure. The objective of this study was to evaluate predictive potential of a positive assay to determine freedom from DNAemia and describe subsequent 3-month CMV outcomes. Adult CMV high-risk kidney and/or pancreas transplant recipients were included if a CMV inSIGHT T Cell Immunity Panel (TCIP, Eurofins Viracor) was ordered and resulted between 1 August, 2019 and 30 July, 2022. Seventy-six patients were included in our study; 49 tested during prophylaxis and 27 during treatment. Most TCIP assays obtained in the prophylaxis cohort were negative (n = 46, 93.9%). Rate of post-TCIP CMV infection was 10.2%. In those tested during treatment, 33.3% were positive and rate of post-TCIP CMV recurrence was 22.2%. The positive predictive value of the assay to successfully predict immunity was 66.7% during both prophylaxis and treatment. There were 4 cases of TCIP predictive failure with progressive CMV replication. At time of replication, 2 patients had concomitant clinical confounders thought to influence immune control of viral replication. All patients had intensification of immunosuppression prior to recurrent replication, but after TCIP was collected. The data obtained from the TCIP are not static, immune control of CMV in latency can change and must be evaluated in clinical context. Timing of TCIP after transplant is significant, and patient-specific factors remain important to assess the likelihood of CMV in each unique patient-specific scenario. A CMV stewardship program can aid in application and interpretation of results.

Risk of cytomegalovirus infection and subsequent allograft failure after pancreas transplantation

Cytomegalovirus (CMV) is a common cause of infection after transplantation, but few studies have evaluated its epidemiology, risk factors, and outcomes among pancreas transplant recipients. We performed a retrospective cohort study of adults who underwent pancreas transplantation from January 1, 2010, through December 31, 2020, at 3 sites in Arizona, Florida, and Minnesota. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or infection requiring antiviral therapy. The secondary outcome was pancreas allograft failure. Among 471 pancreas transplant recipients, 117 (24.8%) developed csCMVi after a median of 226 (interquartile range 154-289) days. CMV donor (D)+/R- patients had a significantly higher incidence of csCMVi (hazard ratio [HR] 4.01, 95% confidence interval [CI] 2.10-7.64; P < .001). In adjusted analysis, a lower absolute lymphocyte count (ALC) was associated with a greater risk of csCMVi among seropositive recipients (HR 1.39 per 50% decrease, 95% CI 1.13-1.73; P = .002) but not among D+/R- patients (HR 1.04 per 50% decrease, 95% CI 0.89-1.23; P = .595). csCMVi, lower ALC, and acute rejection (P < .001) were independently associated with pancreas allograft failure. In conclusion, CMV D+/R- was associated with csCMVi in pancreas recipients, although ALC was associated with csCMVi only among seropositive patients. The development of csCMVi in pancreas recipients was associated with poor pancreas allograft outcomes.

P.29: Use of basiliximab as adjunct maintenance immunosuppressant in pancreas transplant recipients

P.29: Use of basiliximab as adjunct maintenance immunosuppressant in pancreas transplant recipients

P.27: C-peptide: post-transplant trajectory in simultaneous pancreas and kidney transplant recipients

P.27: C-peptide: post-transplant trajectory in simultaneous pancreas and kidney transplant recipients