HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival

Rudolph, E.; Dunn, Ty B.; Mauer, David C.; Noreen, Harriet; Sutherland, David E.R.; Kandaswamy, Raja; Finger, Erik B.

doi:10.1111/ajt.13734

Cited by 34 publications

(27 citation statements)

References 34 publications

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“…It is widely known that HLA matching results in improved outcomes after kidney transplantation [33]. However, the importance of HLA mismatches especially in SPK still remains controversial [34].…”

Section: Discussionmentioning

confidence: 99%

“…Up to six human leukocyte antigen (HLA) mismatches (2 HLA-A, 2 HLA-B, and 2 HLA-DR mismatches) were accepted for transplantation at Hannover Medical School. It is widely known that HLA matching results in improved outcomes after kidney transplantation [ 33 ]. However, the importance of HLA mismatches especially in SPK still remains controversial [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Lo et al found that the number of HLA-A mismatches were associated with an increased risk of acute rejection in SPK patients [ 34 ]. In contrast, Rudolph and colleagues described that HLA mismatch has no significant influence on acute rejection [ 33 ]. It was observed that the number of HLA-B mismatches increases the risk of acute rejection in single pancreas-transplanted patients.…”

Section: Discussionmentioning

confidence: 99%

“…It was observed that the number of HLA-B mismatches increases the risk of acute rejection in single pancreas-transplanted patients. However, the number of HLA-B mismatches could not be significantly associated with an increased risk of acute rejection in patients after SPK [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

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Development and validation of a prognostic model for kidney function 1 year after combined pancreas and kidney transplantation using pre-transplant donor and recipient variables

Zorn

Littbarski

Schwager

et al. 2018

Langenbecks Arch Surg

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PurposeThe widening gap between demand and supply of organs for transplantation provides extraordinary challenges for ethical donor organ allocation rules. The transplant community is forced to define favorable recipient/donor combinations for simultaneous kidney-pancreas transplantation. The aim of this study is the development of a prognostic model for the prediction of kidney function 1 year after simultaneous pancreas and kidney transplantation using pre-transplant donor and recipient variables with subsequent internal and external validation.MethodsIncluded were patients with end-stage renal failure due to diabetic nephropathy. Multivariable logistic regression modeling was applied for prognostic model design with retrospective data from Hannover Medical School, Germany (01.01.2000–31.12.2011) followed by prospective internal validation (01 Jan. 2012–31 Dec. 2015). Retrospective data from another German transplant center in Kiel was retrieved for external model validation via the initially derived logit link function.ResultsThe developed prognostic model is able to predict kidney graft function 1 year after transplantation ≥ KDIGO stage III with high areas under the receiver operating characteristic curve in the development cohort (0.943) as well as the internal (0.807) and external validation cohorts (0.784).ConclusionThe proposed validated model is a valuable tool to optimize present allocation rules with the goal to prevent transplant futility. It might be used to support donor organ acceptance decisions for individual recipients.Electronic supplementary materialThe online version of this article (10.1007/s00423-018-1712-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Development and validation of a prognostic model for kidney function 1 year after combined pancreas and kidney transplantation using pre-transplant donor and recipient variables

Zorn

Littbarski

Schwager

et al. 2018

Langenbecks Arch Surg

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“…The benefits of matching have been seen in all or nearly all types of transplants defined by organ type including heart (27–32), lung (33–36), liver (37–40), and pancreas (41, 42). It should be noted, however, that there are numerous reports of a lack of an effect of HLA matching on outcomes in liver transplantation.…”

Section: Effect Of Hla Matching/mismatching On Outcomesmentioning

confidence: 99%

HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

Zachary

Leffell

2016

Front. Immunol.

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HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching. Furthermore, finding a well-matched donor may not be possible for all patients and usually prolongs waiting time. Strategies to optimize transplantation for patients without a well-matched donor should take into account the immunologic barrier represented by different mismatches: what are the least immunogenic mismatches considering the patient’s HLA phenotype; should repeated mismatches be avoided; is the patient sensitized to HLA and, if so, what are the strengths of the patient’s antibodies? This information can then be used to define the HLA type of an immunologically optimal donor and the probability of such a donor occurring. A probability that is considered to be too low may require expanding the donor population through paired donation or modifying what is acceptable, which may require employing treatment to overcome immunologic barriers such as increased immunosuppression or desensitization. Thus, transplantation must strike a balance between the risk associated with waiting for the optimal donor and the risk associated with a less than optimal donor.

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Donor–recipient human leukocyte antigen A mismatching is associated with hepatic artery thrombosis, sepsis, graft loss, and reduced survival after liver transplant

et al. 2022

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Human leukocyte antigen (HLA) matching is not routinely performed for liver transplantation as there is no consistent evidence of benefit; however, the impact of HLA mismatching remains uncertain. We explored the effect of class I and II HLA mismatching on graft failure and mortality. A total of 1042 liver transplants performed at a single center between 1999 and 2016 with available HLA typing data were included. The median follow‐up period was 9.38 years (interquartile range 4.9–14) and 350/1042 (33.6%) transplants resulted in graft loss and 280/1042 (26.9%) in death. Graft loss and mortality were not associated with the overall number of mismatches at HLA‐A, HLA‐B, HLA‐C, HLA‐DR, and HLA‐DQ loci. However, graft failure and mortality were both increased in HLA mismatching on graft failure and mortality the presence of one (p = 0.004 and p = 0.01, respectively) and two (p = 0.01 and p = 0.04, respectively) HLA‐A mismatches. Elevated hazard ratios for graft failure and death were observed with HLA‐A mismatches in univariate and multivariate Cox proportional hazard models. Excess graft loss with HLA‐A mismatch (138/940 [14.7%] mismatched compared with 6/102 [5.9%] matched transplants) occurred within the first year following transplantation (odds ratio 2.75; p = 0.02). Strikingly, transplants performed at a single all grafts lost due to hepatic artery thrombosis were in HLA‐A–mismatched transplants (31/940 vs. 0/102), as were those lost due to sepsis (35/940 vs. 0/102). In conclusion, HLA‐A mismatching was associated with increased graft loss and mortality. The poorer outcome for the HLA‐mismatched group was due to hepatic artery thrombosis and sepsis, and these complications occurred exclusively with HLA‐A–mismatched transplants. These data suggest that HLA‐A mismatching is important for outcomes following liver transplant. Therefore, knowledge of HLA‐A matching status may potentially allow for enhanced surveillance, clinical interventions in high‐risk transplants or stratified HLA‐A matching in high‐risk recipients.

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HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival

Cited by 34 publications

References 34 publications

Development and validation of a prognostic model for kidney function 1 year after combined pancreas and kidney transplantation using pre-transplant donor and recipient variables

Development and validation of a prognostic model for kidney function 1 year after combined pancreas and kidney transplantation using pre-transplant donor and recipient variables

HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

Donor–recipient human leukocyte antigen A mismatching is associated with hepatic artery thrombosis, sepsis, graft loss, and reduced survival after liver transplant

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