Pancreas Graft Failure Research Articles

Simultaneous Pancreas-Kidney Transplant Outcomes Stratified by Autoantibodies Status and Pretransplant Fasting C-peptide.

Pancreatic beta cell function and islet autoantibodies classically distinguish types of diabetes (type 1 diabetes mellitus [DM] or type 2 DM). Here, we sought to evaluate simultaneous pancreas-kidney (SPK) transplant outcomes stratified by the presence or absence of beta cell function and autoantibodies. SPK recipients were eligible if pretransplant autoantibodies were measured against insulin, islet cell, or glutamic acid decarboxylase 65-kD isoform. Recipients were categorized as A+ or A- based on the detection of ≥1 autoantibodies. Recipients were similarly categorized on the basis of detectable pretransplant fasting C-peptide of ≥2 ng/mL (β+) or <2 ng/mL (β-). Thus, recipients were categorized into 4 groups: A+β-, A-β-, A-β+, and A+β+. Outcomes of interest were overall pancreas graft failure (non-death-censored), death-censored pancreas, or kidney graft failure (death-censored pancreas graft failure [DCGF]; kidney DCGF), composite outcomes with any of the 3 outcomes as pancreas DCGF, use of an antidiabetic agent, or hemoglobin A1c >6.5. One hundred eighty-three SPK recipients were included: A+β- (n = 72), A-β- (n = 42), A-β+ (n = 49), and A+β+ (n = 20). We did not detect a statistical difference in non-death-censored pancreas graft failure for A+β- recipients compared with other groups: A-β- (adjusted hazard ratio [aHR]: 0.44; 95% confidence interval [CI], 0.14-1.42), A-β+ (aHR: 1.02; 95% CI, 0.37-2.85), and A+β+ (aHR: 0.67; 95% CI, 0.13-3.33) in adjusted analyses. Similar outcomes were observed for other outcomes. In SPK recipients, outcomes were similar among recipients with classic features of type 1 DM and various other types of DM.

Risk Factors for Early Post-transplant Weight Changes Among Simultaneous Pancreas-kidney Recipients and Impact on Outcomes.

There are limited data about the risk factors for weight changes and the association of significant weight changes with graft and metabolic outcomes after simultaneous pancreas and kidney (SPK) transplantation. We included all SPK recipients with both allografts functioning for at least 6 mo post-transplant and categorized them based on the weight changes from baseline to 6 mo post-transplant. We analyzed risk factors for significant weight gain (SWG) and significant weight loss (SWL) over 6 mo post-transplant, as well as outcomes including pancreas uncensored graft failure, pancreas death-censored graft failure (DCGF), composite pancreas graft outcomes of DCGF, use of an antidiabetic agent, or hemoglobin A1C >6.5%, and kidney DCGF. Of 280 SPK recipients, 153 (55%) experienced no significant weight change, 57 (20%) SWG, and 70 (25%) SWL. At 6 mo post-transplant, mean weight changes were 1.2% gain in the no significant weight change group, 13.4% gain in SWG, and 9.6% loss in the SWL groups. In multivariate analysis, the only factor associated with decreased risk for weight gain was older recipient age (aOR, 0.97; 95% confidence intervals, 0.95-0.99). Importantly, SWG or SWL were not associated with pancreas graft failure, P-DCGF, or K-DCGF. Interestingly in the adjusted model, SWG at 6 mo was associated with a lower risk for composite outcomes (HR, 0.35; 95% confidence intervals, 0.14-0.85). Forty-five percent of SPK recipients had significant weight changes by 6 mo post-transplant, but only 20% exhibited SWG. Likely because of proper management, weight changes were not associated with poor outcomes post-SPK transplant.

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

Posttransplant erythrocytosis (PTE) is a well-known complication of kidney transplantation. However, the risk and outcomes of PTE among simultaneous pancreas-kidney transplant (SPKT) recipients are poorly described. We analyzed all SPKT recipients at our center between 1998 and 2021. PTE was defined as at least 2 consecutive hematocrit levels of >51% within the first 2 y of transplant. Controls were selected at a ratio of 3:1 at the time of PTE occurrence using event density sampling. Risk factors for PTE and post-PTE graft survival were identified. Of 887 SPKT recipients, 108 (12%) developed PTE at a median of 273 d (interquartile range, 160-393) after transplantation. The incidence rate of PTE was 7.5 per 100 person-years. Multivariate analysis found pretransplant dialysis (hazard ratio [HR]: 3.15; 95% confidence interval [CI], 1.67-5.92; P < 0.001), non-White donor (HR: 2.14; 95% CI, 1.25-3.66; P = 0.01), female donor (HR: 1.50; 95% CI, 1.0-2.26; P = 0.05), and male recipient (HR: 2.33; 95% CI, 1.43-3.70; P = 0.001) to be associated with increased risk. The 108 cases of PTE were compared with 324 controls. PTE was not associated with subsequent pancreas graft failure (HR: 1.36; 95% CI, 0.51-3.68; P = 0.53) or kidney graft failure (HR: 1.16; 95% CI, 0.40-3.42; P = 0.78). PTE is a common complication among SPKT recipients, even in the modern era of immunosuppression. PTE among SPKT recipients was not associated with adverse graft outcomes, likely due to appropriate management.

Impact of removing donation service area and region from pancreas allocation

On March 15, 2021, the Organ Procurement and Transplantation Network (OPTN) replaced donation service area (DSA) and OPTN region as units of pancreas (PA) allocation with a 250 nautical mile (NM) circle with proximity points. We analyzed OPTN data for kidney-pancreas (KP) and PA candidates, transplants, and donors in the 2 years pre-policy (March 16, 2019, to March 14, 2021) and post-policy (March 15, 2021, to March 14, 2023). As expected, more transplants occurred at hospitals outside the recovering organ procurement organization’s DSA post-policy (KP: 32.1% vs 57.3%, P < .001; PA: 61.6% vs 69.3%, P = .09), but the majority stayed within 250 NM (KP: 79.7% vs 85.0%, P < .001; PA: 55.4% vs 61.5%, P = .19). Median preservation time increased from 9.5 to 10.3 hours for KP (P < .001); there was little change for PA (8.5 vs 8.6 hours; P = .99). There were no statistically significant differences in 1-year posttransplant patient mortality or graft failure after implementation for KP (mortality: 3.6% vs 3.2%, P = .60; kidney graft failure: 4.9% vs 5.0%, P = .95; PA graft failure: 9.5% vs 8.9%, P = .65) or PA (mortality: 1.7% vs 2.2%, P = .72; PA graft failure: 12.2% vs 12.6%, P = .88). The removal of DSA and OPTN region from PA allocation has resulted in broader distribution with minimal impact on preservation time or posttransplant outcomes.

Lack of association between deceased pancreas donor LFTs and graft failure or patient mortality

Lack of association between deceased pancreas donor LFTs and graft failure or patient mortality

Lack of association between deceased pancreas donor LFTs and graft failure or patient mortality

Lack of association between deceased pancreas donor LFTs and graft failure or patient mortality

313.1: A novel risk factor for immediate pancreas graft failure: hypertension in the donor

313.1: A novel risk factor for immediate pancreas graft failure: hypertension in the donor

SP5.12 Pancreas Graft Outcome dictates the Renal Graft outcomes and overall patient survival in Simultaneous Kidney Pancreas (SPK) Transplant recipients. A UNOS/OPTN Transplant Registry Big Data Analysis over the last 20 years. An Epidemiology In Transplant Study Group (ETrSG) Initiative

Abstract Purpose Pancreatic graft outcomes affect the cumulative outcomes of SPK transplant, yet the impact of pancreas graft loss on renal graft and overall patient survival is yet to be reported. Methods We harmonized the UNOS/OPTN SPK Transplant data (1996-2019) reported to the U.S. Dept. of Health and Human Services to analyze survival outcomes of recipients who had all cause pancreas graft loss. The demographics report and survival analysis (renal graft/ patient survival) at 1,3, and 5 years post-transplant were data mined. Logistic Regression was done to identify predictors of survival. Results N=7036 all-cause pancreatic graft losses were reported from a cohort of N=64815 SPK Transplant recipients during the first five years of transplant. The renal graft survival was 99%, 97%, and 95% in functioning SPK transplant; 77%, 68%, and 54% in recipients with pancreatic graft loss at 1,3, and 5 years respectively. (Log-rank &amp;lt;0.001). The overall patient survival was 84%, 75%, and 66% in recipients with pancreatic graft loss at 1,3, and 5 years, respectively (Log-rank &amp;lt;0.001). Recipient age &amp;gt;45 years (p=0.008), recipient smoking history ( p&amp;lt;0.001), recipient history of hypertension ( p&amp;lt; 0.001), Recipient BMI &amp;gt;30 (p=0.01), cardiac events ( p=0.02) were the variables of importance on univariate analysis affecting renal graft and patient survival. Recipients with functioning Pancreas had a renal transplant survival benefit (0.22; 0.45) at 1 and 5 years &amp; overall patient survival (0.15; 0.33) at 1 and 5 years respectively. Conclusions Functioning pancreas graft confers survival benefit to renal graft and overall patient survival. The survival deteriorates over time since pancreas graft failure.

Size-mismatched transplantation from large donors to small recipients is associated with pancreas graft thrombosis: A retrospective national observational study.

Donor-recipient (D/R) size mismatch has been evaluated for a number of organs but not for pancreas transplantation. We retrospectively evaluated 438 patients who had undergone pancreas transplantation. The D/R body surface area (BSA) ratio was calculated, and the relationship between the ratio and graft prognosis was evaluated. We divided the patients into two groups and evaluated graft survival. The incidence of pancreas graft thrombosis resulting in graft failure within 14days and 1-year graft survival were compared using Kaplan-Meier curves, and the prognostic factors associated with graft thrombosis were identified by univariate and multivariate analyses. The mean/median donor and recipient BSAs were 1.63m2 /1.65m2 , and 1.57m2 /1.55m2 , respectively; the mean and median D/R BSAs were both 1.05. The receiver operating characteristic curve cutoff for the D/R BSA ratio was 1.09, and significant differences were identified between patients with ratios of ≥1.09 (high group) versus <1.09 (low group). The incidence of graft thrombosis resulting in pancreas graft failure within 14days was significantly higher in the high group than in the low group (p<.01). One-year overall and death-censored pancreas graft survival were significantly higher in the low group than in the high group (p<.01). Multivariate analysis identified recipient height, donor BSA, and donor hemoglobin A1c as significant independent factors for graft thrombosis. Cubic spline curve analysis indicated an increased risk of graft thrombosis with increasing D/R BSA ratio. D/R size mismatch is associated with graft thrombosis after pancreas transplantation.

Impact of Donor Age on Long-Term Outcomes in Simultaneous Pancreas-Kidney Transplantation

Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for type 1 diabetes patients with end-stage renal disease. Donor characteristics are determinants of graft and patient survival. We aimed to study the impact of donor age on outcomes in SPKT. We retrospectively studied 254 patients submitted to SPKT between 2000 and 2021. Patients were classified as "younger donor" (donor age <40 years) and "older donor" (donor age ≥40 years). Fifty-three patients received grafts from older donors. Pancreas graft survival rates at 1, 5, 10, and 15 years were 89%, 83%, 77%, and 73% in the younger donor group, respectively, and 77%, 73%, 67%, and 62% in the older donor group, respectively (P=.052). Older donors and previous major adverse cardiovascular events (MACEs) were associated with pancreas graft failure at 15 years. Kidney transplant survival (1, 5, 10, and 15 years) was lower in the older donor cohort (94%, 92%, 69%, 60% vs 97%, 94%, 89%, and 84%, respectively; P=.004). Older donor, recipient age, and previous MACE predicted kidney graft failure at 15 years. Patient survival rates at 1, 5, 10, and 15 years were 98%, 95%, 91%, and 81% in the younger donor group, respectively, versus 92%, 90%, 84%, and 72% in the older donor group, respectively (P=.127). The kidney graft survival rate was lower in the older donor group, whereas pancreas graft survival and patient survival did not differ significantly. Multivariate analysis showed that a donor age of ≥40 years was an independent predictor of pancreas and kidney graft failure at 15 years in SPKT patients.

Pretransplant C-peptide Levels and Pancreas Transplant Outcomes: Risk and Reward.

We read with interest the report by Parajuli et al1, chronicling the University of Wisconsin experience in simultaneous pancreas-kidney transplantation (SPKT) according to the pretransplant fasting serum C-peptide levels. The authors demonstrated that higher pretransplant C-peptide levels predicted the risk of a composite outcome (combination of pancreas graft failure according to the United Network for Organ Sharing definition and pancreas graft dysfunction defined as initiation of any antidiabetic agent) posttransplant in patients with a type 2 diabetes phenotype.1,2 Recipients were categorized into 3 groups based on pretransplant fasting serum C-peptide levels: low (≤2 ng/mL, n = 14), medium (>2–8 ng/mL, n = 47), and high (>8 ng/mL, n = 15). The uncensored composite outcome of pancreas graft failure or dysfunction occurred in 0% in the low, 23% in the medium, and 33% of patients in the high C-peptide groups, respectively, suggesting that higher levels of pretransplant C-peptide are associated with inferior posttransplant outcomes. These findings confirm our recent report based on a case-controlled, single-center, retrospective study of 46 SPKT patients with pretransplant fasting serum C-peptide levels ≥2.0 ng/mL compared with 46 control patients (C-peptide level <0.5 ng/mL) matched for recipient age, gender, race, and transplant date.3 In our study, we likewise reported inferior mid-term outcomes in the group with higher pretransplant C-peptide levels. In our overall SPKT experience, we have 205 patients with a minimum of 5-y follow-up. Using the above C-peptide categories as per the Wisconsin study, we identified 166 patients in the low, 32 patients in the medium, and 7 patients in the high C-peptide groups. Five-y actual (uncensored) patient and graft survival rates were as follows: patient (91% low versus 93.8% medium versus 85.7% high) and kidney (80.7% versus 71.9% versus 71.4%), respectively. Using the composite end point of pancreas graft failure or dysfunction, pancreas outcomes were 25.3% low versus 34.4% medium versus 71.4% high C-peptide (P = 0.10). Similar to the Wisconsin study, we are limited by the small sample size in the high pretransplant C-peptide group but the findings indicate a trend toward a greater need for supplemental antidiabetic therapy in patients with higher pretransplant C-peptide levels. Unfortunately, what is missing from these studies is a better characterization of patients with partial pancreas allograft function (dysfunction) who continue to be free from wide glycemic excursions and do not experience hypoglycemia (despite the need for antidiabetic therapy) because of preserved counterregulatory function of the pancreas allograft.4 In our experience, we identified posttransplant weight gain, insulin resistance, and rejection as potential mitigating factors to explain these inferior outcomes. Consequently, we recommend greater emphasis on weight management strategies, behavioral modification, nutritional counseling, structured physical training programs, timely adjustments in (and use of less diabetogenic) immunosuppression, more intense long-term monitoring by the transplant center, and increased use of novel antidiabetic agents such as Glucagon-like peptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors when indicated in this unique population. We congratulate the authors on this excellent study and agree that these findings should not be an impetus to limit access to pancreas transplantation but rather help guide clinical decision-making and optimize posttransplant management.

The first 10years of simultaneous pancreas-kidney transplantation in Finland.

Simultaneous pancreas-kidney transplantation (SPK) is an option for patients with type 1 diabetes (T1D) and kidney failure but can be associated with a high complication rate. Here we describe our 10-year experience since the launch of the SPK program. This retrospective study included consecutive patients with T1D receiving SPK from March 14, 2010 to March 14, 2020 at Helsinki University Hospital. Portocaval anastomosis (i.e., systemic venous drainage) and enteric exocrine drainage were used. A specific team was trained for both pancreas retrieval and transplantation, postoperative care was standardized to include somatostatin analogues, antimicrobial treatment, and preoperatively initiated chemothrombopropylaxis. During program maturation donor criteria were expanded and logistical processes improved to minimize cold ischemia time. Clinical data were collected from a nationwide transplantation registry and patient records. A total of 166 SPKs were performed (median 2 per year in the first 3years, 17.5 per year for the following 4years, and 23 per year for the past 3years). Seven patients (4.1%) died with a functioning graft with a median 43months follow-up. One-year pancreas graft survival was 97.0%, 3-year pancreas graft survival was 96.1% and 5-year was 96.1%. Mean HbA1c was 36mmol/mol (SD 5.57) and creatinine was 107μmol/L (SD 34.69) at 1-year after transplantation. All kidney grafts were functioning at the end of follow-up. Complications required re-laparotomy in 39 (23%) patients, mostly due to a pancreas graft related problem (N=28). No pancreas or kidney graft failure from thrombosis occurred. A planned, step-wise development of an SPK program offers a safe and effective treatment for patients with T1D and kidney failure.

Simultaneous Pancreas-kidney Transplantation Candidates With Type 2 Diabetes Mellitus: Elevated C-peptide Levels Warrant Scrutiny, May Portend Worse Outcomes.

Simultaneous Pancreas-kidney Transplantation Candidates With Type 2 Diabetes Mellitus: Elevated C-peptide Levels Warrant Scrutiny, May Portend Worse Outcomes.

Second and Third Chance to Stop Having Diabetes. Pancreas Retransplant With Functional Kidney Graft: A Single-Center Experience

Simultaneous pancreas-kidney (SPK) transplant is the primary option in patients with type 1 diabetes mellitus who develop end-stage kidney disease. Pancreas retransplant (PRt) has become an alternative in patients who experience pancreas graft failure (PGF). There is a lack of evidence regarding PRt in international registers. There are small series of published research with indeed heterogeneous results. We aim to compare PRt outcomes with primary SPK transplant in our center. The study was designed as a descriptive study of a cohort of 234 patients who received SPK transplant and received another PRt because of PGF at Reina Sofía University Hospital between 1988 and 2021. Kaplan-Meier analysis was performed to calculate patient and allograft survival. Of these 234 SPK transplants, 53 pancreas grafts (22.6%) were lost initially. In total, 15 PRts were performed. The major cause of first PGF was surgical, whereas the medical cause was the most frequent in the PRt group. There were 60 deaths in the SPK group compared with only 1 in the PRt group. In Kaplan-Meier analysis, the PRt group showed worse survival than the SPK group, with statistically significant difference between groups (P=.05). Patient survival was not different between both groups. PRt constitutes a viable option for recipients who experience PGF in the absence of formal contraindication. Although graft retransplant survival seems to be inferior to first graft in our series, these results are difficult to compare because of the scarce number of procedures performed.

Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function.

Simultaneous pancreas-kidney transplantation (SPK) carries about a 7%–22% risk of technical failure, but the impact of early pancreas allograft loss on subsequent kidney graft and patient survival is not well-defined. We examined national transplant registry data for type 1 diabetic patients who received SPK between 2000 and 2021. Associations of transplant type (i.e., SPK, deceased‐donor kidney transplant [DDKA], living‐donor kidney transplant [LDKA]) with kidney graft failure and patient survival were estimated by multivariable inverse probability of treatment-weighted accelerated failure-time models. Compared to SPK recipients with a functioning pancreas graft 3 months posttransplant (SPK,P+), LDKA had 18% (Time Ratio [TR] 0.82, 95%CI: 0.70–0.95) less graft survival time and 18% (TR 0.82, 95%CI: 0.68–0.97) less patient survival time, DDKA had 23% (TR 0.77, 95%CI: 0.68–0.87) less graft survival time and 29% (TR 0.71, 95%CI: 0.62–0.81) less patient survival time, and SPK with early pancreas graft loss had 34% (TR 0.66, 95%CI: 0.56–0.78) less graft survival time and 34% (TR 0.66, 95%CI: 0.55–0.79) less patient survival time. In conclusion, SPK,P+ recipients have better kidney allograft and patient survival compared with LDKA and DDKA. Early pancreas graft failure results in inferior kidney and patient survival time compared to kidney transplant alone.

234.4: Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function

Objective: Simultaneous pancreas-kidney transplantation (SPK) is a well-established treatment option for patients with diabetes mellitus and end-stage kidney disease, but SPK carries a 7-22% rate of technical failure. The impact of early pancreas graft function on subsequent kidney graft and patient survival in type 1 diabetic recipients of SPK is not well-defined. Methods: We examined national U.S. transplant registry data for type 1 diabetic patients who received SPK between 2000 and 2021 and survived the first 3 months with a functioning kidney. Transplant patients were categorized as: deceased-donor kidney transplant alone (DDKA), living-donor kidney transplant alone (LDKA), SPK recipients with a functioning pancreas graft 3 months posttransplant (SPK,P+), or SPK recipients with pancreas graft failure within 3 months posttransplant (SPK,P-). Associations of transplant type with kidney graft failure and patient survival through September 2021 were estimated by multivariable inverse probability of treatment weighted (IPTW) accelerated failure-time (AFT) models, with weights estimated using generalized boosted regression. Results: Compared to SPK,P+ recipients, LDKA had 18% less graft survival time (TR: 0.730.820.92) and 18% less patient survival time (TR: 0.720.820.93), DDKA had 23% less graft survival time (TR: 0.710.770.85) and 29% less patient survival time (TR: 0.640.710.79), and SPK,P- had 34% less graft survival time (TR: 0.590.660.75) and 34% less patient survival time (TR: 0.580.660.75). Compared to LDKA, SPK,P- had 19% less graft survival time (TR: 0.700.810.94) and 19% less graft survival time (TR: 0.690.810.95). Compared to DDKA recipients, SPK,P- had 14% less graft survival time (TR: 0.760.860.97). No difference was found for patient survival time between SPK,P- and DDKA. Conclusions: SPK recipients with functioning pancreas grafts within 3-month posttransplant have better kidney allograft and patient survival compared with LDKA and DDKA. Early pancreas graft failure results in inferior kidney and patient survival time compared to kidney transplant alone. This study was supported by grant 4746 from the Foundation for Barnes-Jewish Hospital.

343.4: Pancreas Transplant Outcomes With No Early Graft Loss at A Single Institution

Introduction: The reported 3-month graft failure rate for pancreas allograft remains high ranging from 7-22%. We report outcomes and experience from a single institution with no technical graft loss. Method: A retrospective chart review was conducted of patients who underwent pancreas transplant +/- a kidney transplant from 2012-2021 with a maximum follow-up of five years. Information on pancreas and kidney graft failure was obtained and defined by current 2019 Organ Procurement and Transplantation Network (OPTN) criteria. Results: There were a total 74 patients included. The average age was 47.2 (+/- 9.97) with an average duration of diabetes of 22 years. 35.1% of patients were White, 40.5% Black and 24.3% other. 25% of patients identified as Hispanic. 70% of patients were male and 30% female. 65% of patients had type I diabetes and 35% type II diabetes. Most patients underwent simultaneous pancreas kidney (SPK) transplant (92%). 5.4% had pancreas transplant after kidney (PAK) and 2.7% had a pancreas transplant alone (PTA). The 3-month pancreas and kidney allograft survival was 100%. The 1-year survival for both pancreas and kidney were 97%. 5-year survival for pancreas allograft was 90.4% and 91.8% for kidney allograft. There was no pancreas graft failure due to vascular thrombosis or technical complications. Reasons for failure (n = 8) included post-transplant lymphoproliferative disorder (PTLD), vascular compromise after one year, weight gain with diagnosis of type II diabetes after transplantation for type I diabetes (n= 2), death due to other causes such as burn, graft vs. host disease, chronic obstructive pulmonary disease complications and lung cancer. The causes for kidney graft failure (n=5) included the previous deaths mentioned and PTLD. Conclusion: We report improved survival after pancreas transplantation with no early vascular thrombosis or technical complications and good pancreas and kidney allograft survival due to optimization of technique in addition to protocolized pre- and post-operative management protocol.

The Use of Vasopressors During Deceased Donor Pancreas Procurement Decreases the Risk of Pancreas Transplant Graft Failure

The objective of this study was to identify the effect of various vasopressors on pancreas graft failure and patient survival. A retrospective analysis of the United Network for Organ Sharing database was performed between 2000 and 2019. Patient and graft survival rates were analyzed up to 5 years posttransplant. The data included 17,348 pancreas transplant recipients: 12,857 simultaneous pancreas-kidney, 1440 pancreas transplant alone, and 3051 pancreas-after-kidney transplant recipients. Use of dopamine during deceased donor procurement increased graft failure by 18% (hazard ratio [HR], 1.18; P < 0.001). Absence of vasopressor caused graft failure to rise by 8% (HR, 1.08; P = 0.09). Dopamine increased the mortality rate by 37% (HR, 1.37; P < 0.001) and the absence of vasopressor increased the mortality rate by 14% (HR, 1.14; P = 0.02). Phenylephrine and norepinephrine reduced the mortality rate by 10% (HR, 0.90; P = 0.05) and 11% (HR, 0.89; P = 0.10), respectively. The absence of vasopressor use or the use of dopamine is associated with a higher risk of both pancreas transplant graft failure and recipient mortality. The use of phenylephrine and norepinephrine reduces the risk of mortality. This information should guide deceased donor hemodynamic support management in anticipation of pancreas procurement for future transplantation.

Analysis of Volatile Anesthetic-Induced Organ Protection in Simultaneous Pancreas-Kidney Transplantation.

Background: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia–reperfusion injury (IRI)—Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. Methods: Medical data of 105 patients undergoing SPKT between 1998–2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included “IRI- associated posttransplant clinical outcome” as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for “pancreatic IRI” and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. Results: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17–0.84; p = 0.029). Conclusions: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.

Analyzing outcomes following pancreas transplantation: Definition of a failure or failure of a definition

Pancreas transplantation has an identity crisis and is at a crossroads. Although outcomes continue to improve in each successive era, the number of pancreas transplants performed annually in the United States has been static for several years in spite of increasing numbers of deceased donors. For most practitioners who manage diabetes, pancreas transplantation is considered an extreme measure to control diabetes. With expanded recipient selection (primarily simultaneous pancreas‐kidney transplantation) in patients who are older, have a higher BMI, are minorities, or who have a type 2 diabetes phenotype, the controversy regarding type of diabetes detracts from the success of intervention. The absence of a clear and precise definition of pancreas graft failure, particularly one that lacks a measure of glycemic control, inhibits wider application of pancreas transplantation with respect to reporting long‐term outcomes, comparing this treatment to alternative therapies, developing listing and allocation policy, and having a better understanding of the patient perspective. It has been suggested that the definition of pancreas graft failure should differ depending on the type of pretransplant diabetes. In this commentary, we discuss current challenges regarding the development of a uniform definition of pancreas graft failure and propose a potential solution to this vexing problem.