Objectives: Historical registry analyses have reported inferior outcomes and higher early technical failure rates following pancreas-only retransplant after simultaneous pancreas-kidney transplantation, contri-buting to cautious utilization. Implementation of standardized pancreas graft failure definitions permits contemporary national reassessment of these outcomes.
Materials and Methods: National registry data were extracted to evaluate 7966 adult recipients undergoing primary simultaneous pancreas-kidney transplantation (n = 7895) or pancreas-only retransplant with preserved kidney allograft function (n = 71) between February 2018 and December 2024. Multivariable regression and Cox proportional hazards models assessed pancreas graft failure and mortality.
Results: Among 7966 adult simultaneous pancreas-kidney transplant recipients (7895 primary; 71 pancreas-only retransplant) from 2018 through 2024, retransplant recipients were older (71.8% vs 54.8% aged 40-59 years; P = .007), more frequently White (70.4% vs 46.9%; P = .003), had longer waiting times (627.9 vs 321.5 days; P < .001), longer pancreas preservation time (12.6 vs 10.4 hours; P < .001), and were more often transplanted at high-volume centers (69.0% vs 47.9% at centers with >100 simultaneous pancreas-kidney transplants; P < .001). Retransplant was not independently associated with pancreas graft failure or mortality at 1 year or 3 years. In Cox models, retransplant was not associated with pancreas graft failure (hazard ratio 0.84; P = .683) or mortality (hazard ratio 1.19; P = .544). Increasing recipient age and national sharing independently predicted mortality.
Conclusions: In the contemporary era of standardized pancreas graft failure reporting, pancreas retransplant with preserved kidney function achieves graft and patient survival comparable to primary simultaneous pancreas-kidney transplant nationally. Although retransplant recipients represent a small and highly selected cohort, these population-level data reinforce selective retransplant consideration at experienced centers following pancreas allograft failure.

Key words : Graft failure, Mortality, National registry analysis, Recipient survival

Introduction

Simultaneous pancreas-kidney transplant (SPKT) represents the gold-standard therapy for carefully selected recipients with insulin-dependent diabetes mellitus and end-stage kidney disease, conferring durable insulin independence, restoration of euglycemia, liberation from dialysis and meaningful gains in survival and quality of life.^1-4 Advances in surgical techniques and immunosuppressive protoc-ols and meticulous donor-recipient selection have catalyzed a transformative evolution in outcomes over the past 2 decades. One-year patient survival approaches 98% and approximately 95% at 3 years. Consequently, contemporary United States registry data have shown that SPKT accounts for nearly 90% of all pancreas transplants performed nationally, underscoring its central role in pancreas replacement therapy.^1,5 Despite these triumphs, the field faces a paradox in which a nationwide decline in pancreas transplant volume persists alongside these institu-tional successes.⁶
For the subset of recipients who experience pancreas allograft failure, functionally marked by the return of exogenous insulin dependence and the attendant risks of recurrent diabetes, the path forward is fraught with clinical uncertainty. Graft failure may manifest early as a result of technical or ischemic complications, such as vascular thrombosis, or late as a result of immunologic injury, rejection or chronic allograft dysfunction.⁷ Pancreas retransplant (PRT), specifically following primary SPKT (PRT post-SPKT), has historically been relegated to the periphery of clinical practice. This marginalization largely stems from early registry analyses, now decades old, that reported inferior graft survival, heightened perioperative risks, and questionable utility in the context of scarce donor organs.⁸ Furthermore, the optimal timing for retransplant after early pancreas allograft thrombosis remains undefined, although prior reports suggest that immediate retransplant may yield outcomes comparable to primary pancreas transplant.⁹ Collectively, these factors have fostered a culture of risk aversion, contributing to a decline in retransplant utilization despite the pronounced morbidity inherent to recurrent brittle diabetes.
Notably, these historical perceptions emerged from a pre-standardization era. Before February 2018, the absence of a uniform national definition for pancreas graft failure introduced substantial outco-me misclassification and inter-center reporting variability, limiting the interpretability of national registry analyses and reinforcing conservative attitudes toward PRT. The implementation of the 2018 Organ Procurement and Transplantation Network (OPTN) standardized pancreas graft failure definition estab-lished a consistent national framework for outcome adjudication and longitudinal assessment. Although clinical practice and perioperative management have continued to evolve, contemporary national data evaluating PRT post-SPKT under this uniform definition remain limited. As such, these long-standing assumptions regarding the durability and risk profile of transplantation warrant assessment within the modern pancreas transplant landscape.^10,11
Accordingly, we sought to define graft and reci-pient outcomes of PRT post-SPKT in the modern allocation era. By directly comparing PRT post-SPKT with primary SPKT at a national level, we aimed to delineate clinical durability, survival implications, and the current role of PRT post-SPKT, thereby informing evidence-based decision-making in panc-reas transplantation.

Materials and Methods

Data source
This retrospective registry-based analysis drew upon data from the OPTN, accessed through the United Network for Organ Sharing (UNOS). Adult (aged ≥18 years) recipients who underwent SPKT in the United States between February 28, 2018, and December 31, 2024, were eligible for inclusion. Recipients were categorized as primary SPKT or PRT post-SPKT. The PRT post-SPKT cohort was restricted to pancreas-only retransplant in recipients with retained kidney allografts from the index SPKT, defined as the absence of recorded kidney graft failure in the OPTN registry at the time of retransplant. Exclusion criteria included pediatric recipients, pancreas-after-kidney transplant, panc-reas transplant alone, pancreatic islet cell transplant, and retransplant events involving loss of the kidney allograft following SPKT.

Outcome definitions
The primary outcomes were pancreas allograft failure and recipient mortality. Pancreas graft failure was defined according to the 2018 OPTN standardized definition. Failure was ascertained following graft pancreatectomy, registration for PRT post-SPKT or islet cell transplant after SPKT, sustained insulin use ≥0.5 units/kg/day for ≥90 consecutive days, or when recipient death occurred.¹² Because the OPTN definition incorporates recipient death as a graft failure event, recipient mortality was additionally analyzed as a distinct outcome to mitigate interpre-tive coupling between graft failure and death. Recipient mortality was defined as death from any cause during the follow-up period.

Covariates
Recipient-level variables encompassed age, sex, race and ethnicity, diabetes mellitus status, dialysis status at the time of transplant, body mass index, and duration on the transplant waiting list. Dialysis status reflected OPTN coding at the time of transplant and did not distinguish transient perioperative renal replacement therapy from sustained kidney allograft dysfunction. Race and ethnicity were recorded as documented by the OPTN registry and reflected recipient self-identification or transplant center reporting practices.
Donor-related factors included age, history of diabetes mellitus and hypertension, body mass index at procurement, pancreas preservation time, human leukocyte antigen mismatch level, organ-sharing geography, donation after circulatory death status, and donor cause of death, classified as anoxia, cerebrovascular accident or stroke, head trauma, or central nervous system tumor.
Transplant-specific characteristics comprised transplant-center SPKT volume, interval between primary transplant and retransplant, anastomotic leak, arterial reconstruction approach, abscess or local infection, postoperative pancreatitis, duct management strategy, venous outflow configuration, and utilization of venous jump or extension grafts.

Statistical analyses
We compared baseline recipient, donor, and transplant characteristics between primary SPKT and PRT post-SPKT cohorts using t tests for continuous variables and Pearson χ² tests for categorical variables. We used Kaplan-Meier methods to estimate pancreas allograft survival and recipient survival, with differences assessed using the log-rank test.
We constructed multivariable logistic regression models to evaluate fixed-time outcomes at 1 and 3 years posttransplant for pancreas graft failure and recipient mortality. We used multivariable Cox proportional hazards models to examine time-to-event outcomes over the whole available follow-up period. We presented effect estimates as odds ratios (OR) or hazard ratios (HR) with corresponding 95% CI. We defined statistical significance as 2-sided P values of <.⁰⁵. We used STATA software (version 18E; StataCorp LLC) for analyses.
This study used de-identified data from the OPTN registry. Institutional review board approval was not required in accordance with federal regulations gover-ning secondary analysis of publicly available datasets.

Results

Baseline recipient, donor, and transplant charac-teristics
Among adult SPKT recipients in the United States from 2018 to 2024, baseline characteristics differed between primary SPKT (n = 7895) and PRT post-SPKT (n = 71) cohorts (Table 1). Compared with primary SPKT recipients, those undergoing PRT post-SPKT were older, with fewer recipients aged <40 years (24.0% vs 41.8%; P = .007) and more aged 40 to 59 years (71.8% vs 54.8%).
Racial distribution differed significantly (P = .003), with a higher proportion of White recipients (70.4% vs 46.9%) and a lower proportion of Black (18.3% vs 30.1%) and Hispanic (11.3% vs 17.5%) recipients in the PRT post-SPKT cohort versus the primary SPKT group. At transplant, registry-reported dialysis status (coded by the OPTN at the time of transplant and not reflective of dialysis chronicity) was less frequent among PRT post-SPKT recipients (63.4% vs 78.9%, P = .002), whereas mean wait list duration was more prolonged (627.86 ± 701.72 vs 321.46 ± 417.24 days; P < .001).
Donor age and health metrics were broadly comparable, although mean pancreas preservation time was higher in the PRT post-SPKT cohort (12.60 ± 5.50 vs 10.38 ± 4.29 h; P < .001). Immunologic profiles demonstrated a higher frequency of HLA mismatch level 0 observed among PRT post-SPKT recipients (15.5% vs 0.3%; P < .001). Retransplant was more frequently performed at high-volume centers (>100 SPKT procedures) than primary transplant (69.0% vs 47.9%, P < .001). Surgical techniques, inclu-ding arterial reconstruction, duct management, and venous outflow, and rates of anastomotic leak or postoperative pancreatitis did not differ significantly between SPKT versus PRT post-SPKT cohorts. Reci-pients of PRT post-SPKT more frequently received nationally shared organs (35.2% vs 17.3%, P < .001).

Multivariable predictors of pancreas graft failure and recipient mortality
In multivariable logistic regression analyses eva-luating fixed-time outcomes at 1 and 3 years posttransplant (Table 2), PRT post-SPKT was not independently associated with pancreas graft failure at either 1 year (OR 0.55; 95% CI, 0.24-1.26; P = .155) or 3 years (OR 0.54; 95% CI, 0.28-1.03; P = .062) compared with rates shown for primary SPKT. Recipient race and ethnicity differed with respect to graft failure at 3 years, with higher odds observed among Black (OR 1.18; 95% CI, 1.04-1.34; P = .011) and Hispanic recipients (OR 1.38; 95% CI, 1.18-1.61; P < .001), whereas no significant associations were observed at 1 year.
Organ-sharing geography was a significant predictor of graft failure at both time points, for regional sharing at 1 year (OR 1.39; 95% CI, 1.20-1.62; P < .001) and at 3 years (OR 1.86; 95% CI, 1.62-2.14; P < .001) and for national sharing at 1 year (OR 1.94; 95% CI, 1.68-2.25; P < .001) and at 3 years (OR 3.09, 95% CI 2.66–3.59; P < .001) compared with local sharing. Higher transplant-center volume (>100 SPKT) was associated with lower odds of graft failure at 1 year (OR 0.69; 95% CI, 0.59-0.81; P < .001), with no significant difference seen at 3 years.
In analyses of mortality, PRT post-SPKT was not an independent predictor at 1 year (OR 0.41; 95% CI, 0.06-2.95; P = .374) or at 3 years (OR 1.05; 95% CI, 0.38-2.90; P = .929). Increasing recipient age revealed higher odds of mortality for recipients aged 40 to 59 years at 1 year (OR 1.62; 95% CI, 1.21-2.18; P = .001) and at 3 years (OR 1.45; 95% CI, 1.16-1.81; P = .001) and for recipients aged ≥60 years at 1 year (OR 2.25; 95% CI, 1.22-4.13; P = .009) and at 3 years (OR 2.63; 95% CI, 1.69-4.10; P < .001) compared with recipients aged 18 to 39 years. National organ sharing had higher odds of mortality at both 1 year (OR 1.99; 95% CI, 1.45-2.73; P < .001) and 3 years (OR 1.48; 95% CI, 1.14-1.91; P = .003).

Time-to-event analyses of pancreas allograft failure and recipient mortality
In multivariable Cox proportional hazards analyses assessing time-to-event outcomes over the whole follow-up period (Table 3), PRT post-SPKT did not confer a higher hazard of pancreas graft failure (HR 0.84, 95% CI, 0.37-1.93; P = .683) or recipient mortality (HR 1.19, 95% CI, 0.67-2.12; P = .544) compared with primary SPKT.
Regarding pancreas graft failure, donor- and geography-related factors had measurable effects on longitudinal risk. A history of donor hypertension corresponded to an increased hazard of graft failure (HR 1.46, 95% CI, 1.06-2.01; P = .019). Relative to locally shared organs, both regional (HR 1.25, 95% CI, 1.05-1.49; P = .012) and nationally shared organs (HR 1.32, 95% CI, 1.10-1.59; P = .003) exhibited elevated hazards of graft loss.
Recipient mortality varied across clinical and allocation-related factors. Increasing age was accom-panied by progressively higher mortality risk, including recipients aged 40 to 59 years (HR 1.31, 95% CI, 1.13-1.52; P < .001) and those aged ≥60 years (HR 2.54, 95% CI, 1.89-3.42; P < .001), relativeto recipients aged 18 to 39 years. Dialysis status at the time of transplant was linked to higher mortality risk (HR 1.26, 95% CI, 1.05-1.51; P = .011), as were donor hypertension (HR 1.54, 95% CI, 1.13-2.09; P = .006) and donor BMI >35 kg/m² at procurement (HR 2.16, 95% CI, 1.07-4.35; P = .032). Compared with local sharing, national organ sharing had a higher mortality risk (HR 1.56, 95% CI, 1.28-1.92; P = .001), whereas regional sharing was not.
Unadjusted Kaplan-Meier analysis depicted com-parable longitudinal trajectories between primary transplant and retransplant for both pancreas graft survival (Figure 1) and recipient survival (Figure 2).

Discussion

In this national registry analysis restricted to the post-2018 era of standardized pancreas graft failure reporting, pancreas-only retransplant after prior simultaneous pancreas-kidney transplant in patients with preserved kidney allograft function was not associated with inferior pancreas graft or recipient survival compared with primary SPKT. Although the PRT post-SPKT cohort was small (n = 71), adjustment for recipient-, donor-, and transplant-related factors yielded comparable fixed-time graft failure and mortality at 1 year, as well as similar longitudinal survival trajectories over extended follow-up.
Recipients undergoing PRT post-SPKT were older, experienced longer wait list durations, and differed in pretransplant renal replacement status, reflecting selective retransplant candidacy rather than differences in renal disease severity. Despite elevated baseline risk, outcomes following PRT post-SPKT paralleled those observed after primary SPKT, chal-lenging historical perceptions regarding retransplant futility rooted in registry-era analyses predating standardized outcomes definitions.
The introduction of the 2018 OPTN pancreas graft failure definition enabled consistent national outcomes ascertainment and mitigated reporting variability that previously limited interpretation of pancreas transplant durability. Moreover, retransplant status itself did not emerge as an independent determinant of adverse graft or patient outcomes, suggesting that modern candidate selection, peri-operative management, and center expertise may reduce risk historically attributed to pancreas retransplantation.^10,12

Clinical and institutional determinants of retransplant outcomes
Graft and patient outcomes following PRT post-SPKT were related primarily to recipient-level characteristics rather than retransplant status itself. Recipient age and dialysis status at the time of transplant were the strongest predictors of mortality, mirroring well-established risk gradients observed in primary SPKT populations. Prior literature consistently demonstrated higher mortality among older primary SPKT recipients and those requiring dialysis pretransplant.^13-15
In the present cohort, recipients aged ≥60 years experienced higher early and long-term mortality without a corresponding increase in graft failure. This age-associated mortality gradient is consistent with prior pancreas transplant literature demonstrating increased mortality with advancing recipient age and does not indicate a retransplant-specific risk effect. Although data specific to retransplant populations remain limited, the observed pattern aligns with broader transplant experience.^16,17 Dialysis at transplant was less frequent among PRT post-SPKT recipients compared with primary SPKT recipients, reflecting selective retransplant candidacy rather than uniform preservation of kidney allograft function.¹⁸
Donor characteristics further shaped longitudinal outcomes. Donor hypertension conferred elevated hazards of both graft failure and mortality, empha-sizing the importance of donor vascular integrity in extant pancreas transplant. Notably, evidence supports donor hypertension as an independent factor asso-ciated with reduced graft survival.¹⁹
Overall, these recipient- and donor-level patterns underscore that retransplant outcomes are governed primarily by established clinical risk factors rather than retransplant per se. As in primary SPKT, careful appraisal of immunologic risk, surgical feasibility, comorbidity burden, and psychosocial readiness remains essential to candidate selection. Notably, PRT post-SPKT recipients demonstrated a distinct baseline immunologic profile, including enrichment of zero HLA mismatch. However, HLA mismatch was not retained as an independent predictor of pancreas graft failure or mortality in adjusted models, suggesting that contemporary outcomes are not explained by immunologic matching alone.
Data evaluating race and ethnicity in the context of PRT post-SPKT have been sparse. In the present cohort, White recipients were overrepresented among retransplant recipients, whereas Black and Hispanic recipients were less frequently represented relative to primary SPKT. These distributional differences warrant cautious interpretation, as race and ethnicity in registry data reflect social rather than biological constructs. Potential explanations include variation in referral pathways, surgical candidacy and structural barriers to retransplant access.^20,21 The absence of granular data on sensitization burden, socioeconomic status and center-level referral prac-tices limits further inference.
Institutional experience also appears to influence early graft outcomes. Lower-volume transplant centers showed higher odds of 1-year graft failure, consistent with prior reports linking procedural volume to early pancreas allograft viability.²² This relationship likely reflects differences in technical expertise, perioperative coordination, and postoperative surveillance, with higher-volume centers benefiting from accumulated procedural experience and specialized infrastructure.²² Although prior knowledge does not offer insight into mortality differences across center volume strata,²³ the technical and immunologic intricacies inherent to PRT post-SPKT underline the importance of institutional expertise in mitigating early graft risk.

Reconsideration of historical registry-era conclusions
The use of PRT post-SPKT has historically been approached with caution, mainly informed by early registry analyses reporting inferior graft survival, elevated perioperative risk, and concerns on allocation of finite donor organs.⁸ These reports promulgated the prevailing perception that pancreas retransplant should be reserved for highly selected cases, particularly when glycemic control could be medically achieved. Concerns regarding wait list attrition among candidates with prior organ transplant further narrowed retransplant candidacy, as prolonged wait times were associated with dropout due to death or clinical deterioration.²⁴ In parallel, retransplant candidacy is further narrowed by the availability of nonoperative alternatives in select patients, including intensified insulin regimens and islet-based approaches, thereby reducing retransplant utilization even when recurrent brittle diabetes imposes substantial morbidity.^25,26
Prior registry analyses demonstrated that panc-reas graft failure after SPKT is associated with a substantial survival penalty, including reported 2- to 3-fold increases in mortality risk compared with recipients maintaining pancreas graft function.^25-29 Importantly, this penalty does not appear immutable. High-volume single-center series reported that pancreas retransplant can achieve graft and patient survival in select recipients.^25,30–33 In selected cohorts, retransplant has been associated with improved survi-val compared with non-retransplant manage­ment following pancreas graft loss.³⁴ Beyond mortality, recurrent brittle diabetes following pancreas graft loss imposes profound metabolic instability and quality-of-life impairment, reinforcing the clinical and metabolic significance of pancreas graft failure inde-pendent of preserved kidney allograft function.^24,26 A landmark UNOS registry analysis spanning the late 1990s through 2012 reported markedly lower death-censored pancreas graft survival among retransplant recipients compared with primary SPKT recipients, with graft survival approximating 37% at 1 year, 21% at 3 years, and 14% to 15% at 5 years.⁸ Although recipient survival was relatively preserved, these observations cemented concerns on early technical failure and limited graft longevity, contri-buting to sustained center-level reluctance to pursue retransplant.
In contrast to prior registry studies that pooled heterogeneous retransplant populations, including pancreas-after-kidney and pancreas-alone transplant, the present analysis focuses exclusively on repeat SPKT, enabling organ- and procedure-specific interpre-tation. The use of PRT post-SPKT is uncommon and is concentrated among appropriately selected can-didates treated at experienced transplant centers. These findings suggest that historical perceptions of retransplant futility reflect limitations of earlier data and practice patterns rather than the intrinsic inferiority of pancreas retransplant.
Importantly, these registry-based observations should be interpreted within the context of a substan-tial body of single-center literature demonstrating that pancreas retransplant can be performed with acceptable graft and patient survival in carefully selected recipients at experienced centers. Prior institutional series have reported favorable short- and mid-term outcomes following pancreas retransplant, while emphasizing the influence of retransplant timing, etiology of initial graft loss, sensitization burden, and operative complexity on graft survival.^25,30-35 These variables cannot be fully disentangled within national registry databases. Rather than contradicting these reports, this present national analysis complements them by demonstrating comparable outcomes under the standardized panc-reas graft failure definition implemented by the OPTN. Accordingly, these insights should be interpreted as confirmatory of modern practice patterns rather than as a refutation of established single-center experience.^{30,31,33,36,37}

Evolving surgical and immunologic context
Repeat SPKT is performed in a hostile surgical environment shaped by prior iliac vessel utilization and dense intra-abdominal adhesions, which histo-rically magnified technical risk and tempered enthusiasm for retransplantation.^30,36,37 Although such anatomic constraints persist, contemporary operative planning and reconstruction strategies appear to mitigate many early technical failure modes. In our analyzed cohort, longer preservation times among PRT post-SPKT recipients likely reflected this procedural complexity rather than diminished graft quality. Moreover, postoperative complications, including graft pancreatitis, anasto-motic leaks, and infection, did not significantly differ between cohorts. Although pancreas-specific comp-lications were comparable, prior single-center expe-rience suggested that repeat SPKT may be associated with transient perioperative delayed graft dysfunction requiring temporary dialysis despite preserved long-term renal allograft survival, consistent with operative burden rather than irreversible kidney allograft failure.³⁶
Although HLA matching plays a key role in solitary pancreas transplant, it did not independently affect graft survival for patients with PRT post-SPKT. This observation aligns with prior analyses de-monstrating no independent association between HLA mismatch and pancreas graft survival.³⁴ Subsequently, evidence has highlighted that modern desensitization protocols, incorporating rituximab, plasmapheresis, and intravenous immunoglobulin, can effectively manage the challenges of the highly sensitized recipient.³⁸
In this context, the absence of an independent association between retransplant status and graft failure or mortality indicates that retransplant should no longer be viewed as an inherent marker of prohibitive surgical or immunologic risk. Instead, outcomes appear to be shaped by an elaborate interplay of recipient characteristics, donor quality, and the concentration of these procedures at high-volume centers. By moving beyond legacy surgical fears and outdated immunologic dogmas, the transplant community can more accurately identify candidates for whom PRT post-SPKT offers a life-extending secondary therapy rather than a futile gamble.

Methodological considerations and registry constraints
In our study, restriction of analysis to the post-2018 era of standardized pancreas graft failure reporting improved consistency in outcome classification and enhanced the reliability of longitudinal graft survival assessment. By limiting the cohort exclusively to pancreas-only retransplant following primary SPKT with retained kidney allografts, heterogeneity intro-duced by mixed retransplant populations (such as pancreas-after-kidney or pancreas transplant alone) is avoided, allowing SPKT-specific interpretation of outcomes. The use of multivariable regression and time-to-event analyses permitted evaluation of the independent association of retransplant status with graft and recipient outcomes after adjustment for key recipient-, donor-, and center-level factors.
Limitation to the contemporary standardized graft-failure era resulted in a relatively small PRT post-SPKT cohort (n = 71), constraining statistical power to detect modest effect sizes or rare comp-lications. Although the 2018 OPTN policy established a unified national definition for pancreas graft failure, reports after implementation have shown incomplete uptake of key data elements. Consequently, some degree of outcome misclassification may persist despite standardization.¹²
Although the interval from index SPKT to retransplant and sensitization metrics are available within the OPTN registry, the database lacks the clinical granularity necessary to comprehensively characterize the heterogeneity inherent to pancreas retransplant. Specifically, the registry does not reliably differentiate technical graft loss from immunologic failure; in addition, the registry does not capture operative complexity, extent of intra-abdominal adhesiolysis, iliac vessel accessibility, vascular reconstruction constraints, or timing of prior graft explantation. Early reoperative retransplant for technical thrombosis and late retransplant for chronic immunologic failure represent fundamentally distinct surgical and immunologic entities with different risk profiles yet cannot be extricated within registry-based analyses. To preserve model stability within a limited retransplant cohort, sensitization variables and retransplant timing were not incorporated into the present multivariable analyses. Institutional retransp-lant series have described the heightened immunologic complexity of repeat pancreas transplant, including increased acute rejection rates and differential outcomes based on retransplant timing.^30,33 Circu-lating donor-specific alloantibodies and elevated calculated panel reactive antibody levels have been associated with pancreas graft failure in contem-porary cohorts.³⁹ Therefore, residual immunologic and temporal confounding cannot be excluded.
Our analysis was further constrained by the limitations within the OPTN registry. The database does not capture the indication, acuity, or duration of dialysis at the time of retransplant. Among PRT post-SPKT recipients receiving dialysis at transplant (n = 45), registry data do not clearly attribute dialysis to sustained kidney allograft dysfunction meeting OPTN eligibility criteria from perioperative renal replacement therapy surrounding pancreas retransplant. Importantly, OPTN dialysis coding does not distinguish chronic renal replacement therapy from transient reoperative dialysis or delayed graft function following complex abdominal surgery. This distinction is clinically meaningful, as prior surgical series have documented that repeat abdominal transplant procedures are associated with higher perioperative complication rates and delayed graft function requiring hemodialysis despite preserved long-term renal allograft survival.³⁶ Accordingly, dialysis status at retransplant should not be interpreted as evidence of kidney graft failure or misclassification of retransplant type.
In addition, the registry lacks data on periope-rative renal insults, dialysis frequency, hematologic parameters, immunologic mechanisms, and center-specific immunosuppressive protocols, limiting detailed interpretation of transient renal dysfunction.
Finally, the predominance of both primary SPKT and PRT post-SPKT procedures at higher-volume transplant centers suggests that favorable outcomes likely reflect institutional expertise, multidisciplinary infrastructure, and selective candidate evaluation. Given the observational design of this national registry analysis, these findings may not be generalizable to lower-volume settings and are best interpreted as contemporary national benchmarks rather than defi-nitive estimates of long-term graft viability.

Clinical interpretation and conclusions
In the modern era characterized by standardized graft failure definitions and refined surgical expertise, PRT post-SPKT achieves graft and patient survival compa-rable to primary pancreas transplant. Multivariable analysis indicated that retransplant status was not an independent predictor of adverse outcomes. Although retransplant remains uncommon and highly selected, the absence of excess risk attributable to retransplant status suggests that contemporary national outcomes no longer support the historical perception of retransplant futility. Rather, outcomes appear to be driven primarily by recipient age, donor health metrics, and institutional volume. These findings underscore that retransplant candidacy is best conceptualized through individualized risk strati-fication rather than categorical assumptions regarding retransplant status alone. When performed at experienced centers with careful donor selection and operative planning, PRT post-SPKT may offer durable metabolic benefit for selected recipients experiencing isolated pancreas allograft failure despite optimized medical management.

References:

1. Gruessner AC, Gruessner RW. The current state of pancreas transplantation in the USA–a registry report. Curr Transplant Rep. 2018;5(4):304-314. doi:10.1007/s40472-018-0213-x
   CrossRef - PubMed
2. Gruessner AC, Gruessner RW. The 2022 International Pancreas Transplant Registry Report-a review. Transplant Proc. 2022;54(7):1918-1943. doi:10.1016/j.transproceed.2022.03.059
   CrossRef - PubMed
3. Esmeijer K, Hoogeveen EK, van den Boog PJM, et al. Superior long-term survival for simultaneous pancreas–kidney transplantation as renal replacement therapy: 30-year follow-up of nationwide cohort. Diabetes Care. 2020;43(2):321-328. doi:10.2337/dc19-1580
   CrossRef - PubMed
4. Venkatanarasimhamoorthy VS, Barlow AD. Simultaneous pancreas–kidney transplantation versus living donor kidney transplant alone: an outcome–driven choice? Curr Diab Rep. 2018;18(9):67. doi:10.1007/s11892-018-1039-8
   CrossRef - PubMed
5. Kandaswamy R, Stock PG, Miller JM, Handarova D, Israni AK, Snyder JJ. OPTN/SRTR 2023 annual data report: pancreas. Am J Transplant. 2025;25(2S1):S138-S192. doi:10.1016/j.ajt.2025.01.021
   CrossRef - PubMed
6. Parsons RF, Lentine KL, Doshi M, et al. Generating strategies for a national comeback in pancreas transplantation: a delphi survey and U.S. conference report. Am J Transplant. 2024;24(8):1473-1485. doi:10.1016/j.ajt.2024.03.010
   CrossRef - PubMed
7. Masset C, Branchereau J, Buron F, et al. The role of donor hypertension and angiotensin II in the occurrence of early pancreas allograft thrombosis. Front Immunol. 2024;15:1359831. doi:10.3389/fimmu.2024.1359381
   CrossRef - PubMed
8. Siskind E, Maloney C, Jayaschandaran V, et al. Pancreatic retransplantation is associated with poor allograft survival: an update of the United Network of Organ Sharing database. Pancreas. 2015;44(5):769-772. doi:10.1097/MPA.0000000000000330
   CrossRef - PubMed
9. Hollinger EF, Powelson JA, Mangus RS, et al. Immediate retransplantation for pancreas allograft thrombosis. Am J Transplant. 2009;9(4):740–745. doi:10.1111/j.1600-6143.2009.02517.x
   CrossRef - PubMed
10. United Network for Organ Sharing. Definition of pancreas graft failure. June 2015. Accessed November 7, 2025. https://unos.org/wp-content/uploads/unos/Definition-of-Pancreas-Graft-Failure.pdf
    CrossRef - PubMed
11. Niederhaus SV, Carrico RJ, Prentice MA, et al. C-peptide levels do not correlate with pancreas allograft failure: multicenter retrospective analysis and discussion of the new OPTN definition of pancreas allograft failure. Am J Transplant. 2019;19(4):1178-1186. doi:10.1111/ajt.15118
    CrossRef - PubMed
12. Casey MJ, Murakami N, Ong S, et al. Medical and surgical management of the failed pancreas transplant. Transplant Direct. 2023;10(1):e1543. doi:10.1097/TXD.0000000000001543
    CrossRef - PubMed
13. Shingde R, Calisa V, Craig JC, et al. Relative survival and quality of life benefits of pancreas–kidney transplantation, deceased kidney transplantation and dialysis in type 1 diabetes mellitus-a probabilistic simulation model. Transpl Int. 2020;33(11):1393-1404. doi:10.1111/tri.13679
    CrossRef - PubMed
14. Dong Y, Zhou J, Xiang J, et al. Influence of dialysis duration on outcomes of simultaneous pancreas–kidney transplant. Clin Transplant. 2021;35(4):e14238. doi:10.1111/ctr.14238
    CrossRef - PubMed
15. Mittal S, Smilevska R, Franklin R, et al. An analysis of the association between older recipient age and outcomes after whole–organ transplantation – a single–centre, retrospective study. Transpl Int. 2020;33(5):529-535. doi:10.1111/tri.13575
    CrossRef - PubMed
16. Laurence JM, Marquez MA, Seal JB, et al. The effect of recipient age on outcome after pancreas transplantation. Transplantation. 2015;99(2):e13-e14. doi:10.1097/TP.0000000000000554
    CrossRef - PubMed
17. Shah AP, Mangus RS, Powelson JA, et al. Impact of recipient age on whole organ pancreas transplantation. Clin Transplant. 2013;27(1):E49-E55. doi:10.1111/ctr.12047
    CrossRef - PubMed
18. Parajuli S, Arunachalam A, Swanson KJ, et al. Pancreas retransplant after pancreas graft failure in simultaneous pancreas–kidney transplant is associated with better kidney graft survival. Transplant Direct. 2019A;5(8):e473. doi:10.1097/TXD.0000000000000919
    CrossRef - PubMed
19. Hu ZH, Gu YJ, Qiu WQ, et al. Pancreas grafts for transplantation from donors with hypertension: an analysis of the scientific registry of transplant recipients database. BMC Gastroenterol. 2018;18(1):141. doi:10.1186/s12876-018-0865-0
    CrossRef - PubMed
20. Mahajan S, Caraballo C, Lu Y, et al. Trends in differences in health status and health care access and affordability by race and ethnicity in the United States, 1999–2018. JAMA. 2021;326(7):637-648. doi:10.1001/jama.2021.9907
    CrossRef - PubMed
21. Roberts SE, Rosen CB, Keele LJ, et al. Rates of surgical consultations after emergency department admission in Black and White Medicare patients. JAMA Surg. 2022;157(12):1097-1104. doi:10.1001/jamasurg.2022.4959
    CrossRef - PubMed
22. Alhamad T, Malone AF, Brennan DC, et al. Transplant center volume and the risk of pancreas allograft failure. Transplantation. 2017;101(11):2757-2764. doi:10.1097/TP.0000000000001628.
    CrossRef - PubMed
23. Kim Y, Dhar VK, Wima K, et al. The center volume–outcome effect in pancreas transplantation: a national analysis. J Surg Res. 2017;213:25-31. doi:10.1016/j.jss.2017.02.025
    CrossRef - PubMed
24. Shirley C, Tatum D, Killackey M, Jeon H, Paramesh A, Vijay A. Balancing waitlist dropout in pancreas transplantation. Transplant Proc. 2023;55(3):613-615. doi:10.1016/j.transproceed.2023.02.046
    CrossRef - PubMed
25. Pillokeit N, Grzella S, Zgoura P, Westhoff T, Viebahn R, Schenker P. Challenges associated with pancreas and kidney retransplantation–a retrospective analysis. J Clin Med. 2021;10(16):3634. doi:10.3390/jcm10163634
    CrossRef - PubMed
    
    
26. Gruessner RWG, Gruessner AC. Pancreas transplantation alone for brittle diabetes mellitus. ES J Case Rep. 2023;4(2):1044. doi:10.59152/ESJCR/1044
    CrossRef - PubMed
27. Salvalaggio PR, Dzebisashvili N, Pinsky B, et al. Incremental value of the pancreas allograft to the survival of simultaneous pancreas–kidney transplant recipients. Diabetes Care. 2009;32(4):600-602. doi:10.2337/dc08-1718
    CrossRef - PubMed
28. Norman SP, Kommareddi M, Ojo AO, Luan FL. Early pancreas graft failure is associated with inferior late clinical outcomes after simultaneous kidney-pancreas transplantation. Transplantation. 2011;92(7):796-801. doi:10.1097/TP.0b013e31822dc36b
    CrossRef - PubMed
29. Ji M, Wang M, Hu W, et al. Survival after simultaneous pancreas–kidney transplantation in type 1 diabetes: the critical role of early pancreas allograft function. Transpl Int. 2022;35:10618. Published 2022 Sep 12. doi:10.3389/ti.2022.10618
    CrossRef - PubMed
30. Rudolph EN, Finger EB, Chandolias N, Kandaswamy R, Sutherland DER, Dunn TB. Outcomes of pancreas retransplantation. Transplantation. 2015;99(2):367-374. doi:10.1097/TP0000000000000566
    CrossRef - PubMed
31. Buron F, Thaunat O, Demuylder-Mischler S, et al. Pancreas retransplantation: a second chance for diabetic patients? Transplantation. 2013;95(2):347-352. doi:10.1097/TP.0b013e318271d795
    CrossRef - PubMed
32. Seal J, Selzner M, Laurence J, et al. Outcomes of pancreas retransplantation after simultaneous kidney-pancreas transplantation are comparable to pancreas after kidney transplantation alone. Transplantation. 2015;99(3):623-628. doi:10.1097/TP.0000000000000383
    CrossRef - PubMed
33. Gasteiger S, Cardini B, Göbel G, et al. Outcomes of pancreas retransplantation in patients with pancreas graft failure. Br J Surg. 2018;105(3):1816-1824. doi:10.1002/bjs.10929
    CrossRef - PubMed
34. Ollinger R, Margreiter C, Bösmüller C, et al. Evolution of pancreas transplantation: long-term results and perspectives from a high-volume center. Ann Surg. 2012;256(5):780-787. doi:10.1097/SLA.0b013e3182878ec0
    CrossRef - PubMed
35. Fridell JA, Milgrom ML, Henson S, Pescovitz MD. Use of the end-to-end anastomotic circular stapler for creation of the duodenoenterostomy for enteric drainage of the pancreas allograft [corrected]. J Am Coll Surg. 2004;198(3):495-497. doi:10.1016/j.jamcollsurg.2003.09.006
    CrossRef - PubMed
36. LaMattina JC, Sollinger HW, Becker YT, Mesrich JD, Pirsch JD, Odorico JS. Simultaneous pancreas and kidney (SPK) retransplantation in prior SPK recipients. Clin Transplant. 2012;26(3):495-501. doi:10.1111/j.1399-0012.2011.01540.x
    CrossRef - PubMed
37. Dunn TB, Sutherland DER. Repeat pancreas transplant procedures: recipient selection and surgical techniques. Curr Transpl Rep. 2014;1:119-123. doi:10.1007/s40472-014-0014-9
    CrossRef - PubMed
38. Kykalos S, Wunsch A, Klein T, Viebahn R, Schenker P. Successful simultaneous pancreas–kidney re-transplantation in a highly human leukocyte antigen-sensitized patient. Transplant Proc. 2017;49(7):1652-1655. doi:10.1016/j.transproceed.2017.05.005
    CrossRef - PubMed
39. Parajuli S, Alagusundaramoorthy S, Aziz F, et al. Outcomes of pancreas transplant recipients with de novo donor-specific antibodies. Transplantation. 2019B;103(2):435-440. doi:10.1097/TP.0000000000002339
    CrossRef - PubMed