Faculty Bibliography

BACKGROUND: Recipients of ABO-incompatible (ABOi) living-donor kidney transplants often undergo more intense immunosuppression than their ABO-compatible counterparts. It is unknown if this difference leads to higher cancer risk after transplantation. Single-center studies are too small and lack adequate duration of follow-up to answer this question. METHODS: We identified 318 ABOi recipients in the Transplant Cancer Match Study, a national linkage between the Scientific Registry of Transplant Recipients and population-based U.S. cancer registries. Seven cancers (non-Hodgkin lymphoma, Merkel cell carcinoma, gastric adenocarcinoma, hepatocellular carcinoma, thyroid cancer, pancreatic cancer, and testicular cancer) were identified among ABOi recipients. We then matched ABOi recipients to ABO-compatible controls by age, gender, race, human leukocyte antigen mismatch, retransplantation, and transplant year. RESULTS: There was no demonstrable association between ABOi and cancer in unadjusted (incidence rate ratio, 0.83; 95% confidence interval, 0.33-1.71; P=0.3) or matched control (incidence rate ratio, 0.99; 95% confidence interval, 0.38-2.23; P=0.5) analyses. CONCLUSION: To the extent that could be determined in this registry study, current desensitization protocols are not associated with increased risk of cancer after transplantation.

For many devastating injuries and tissue defects where conventional reconstruction is not possible, reconstructive transplantation such as hand and face transplantation has become a viable alternative. This novel approach allows for improved restoration of appearance, anatomy and function not feasible by other available treatment options. However, clinical management of these injuries prior to transplantation frequently requires multiple blood transfusion or skin grafts resulting in the formation of alloantibodies (anti-HLA IgG Abs) and a high degree of sensitization. The role of donor-specific antibodies (DSA) and mechanisms of antibody-mediated rejection (AMR) in reconstructive transplantation are still largely unknown. Thus there is an imminent need to develop a better understanding of the mechanisms related to DSA and AMR after reconstructive transplantation. In this review, we will define the role of DSA and mechanisms of AMR in reconstructive transplantation and compare them to established measures and treatment concepts in solid organ transplantation.

PURPOSE OF REVIEW: Humoral sensitization to antigens of the human leukocyte antigen and ABO systems remains one of the largest barriers to further expansion in renal transplantation. This barrier translates into prolonged waiting time and a greater likelihood of death. The number of highly sensitized patients on the renal transplant waiting list continues to increase. This review focuses on the options available to these patients and speculates on future directions for incompatible transplantation. RECENT FINDINGS: Desensitization protocols (to remove antibodies), kidney-paired donation (to circumvent antibodies) or a hybrid technique involving a combination of both have broadened the access to transplantation for patients disadvantaged by immunologic barriers. However, the risk of antibody-mediated rejection may be increased and warrants caution. Technical advances in antibody characterization using sensitive bead immunoassays and the C1q assay and therapeutic modalities such as complement inhibitors and proteasome inhibitors have been used to avoid or confront these antibody incompatibilities. SUMMARY: A growing body of knowledge and literature indicates that these diagnostic and therapeutic modalities can facilitate a safer and more successful treatment course for these difficult-to-treat patients. Rigorous investigations into newer interventions will help in broadening the options for these patients and also expand the living donor pool.

With many multicenter consortia and a United Network for Organ Sharing program, participation in kidney paired donation (KPD) has become mainstream in the United States and should be feasible for any center that performs live donor kidney transplantation (LDKT). Lack of participation in KPD may significantly disadvantage patients with incompatible donors. To explore utilization of this modality, we analyzed adjusted center-specific KPD rates based on casemix of adult LDKT-eligible patients at 207 centers between 2006 and 2011 using SRTR data. From 2006 to 2008, KPD transplants became more evenly distributed across centers, but from 2008 to 2011 the distribution remained unchanged (Gini coefficient = 0.91 for 2006, 0.76 for 2008 and 0.77 for 2011), showing an unfortunate stall in dissemination. At the 10% of centers with the highest KPD rates, 9.9-38.5% of LDKTs occurred through KPD during 2009-2011; if all centers adopted KPD at rates observed in the very high-KPD centers, the number of KPD transplants per year would increase by a factor of 3.2 (from 494 to 1593). Broader implementation of KPD across a wide number of centers is crucial to properly serve transplant candidates with healthy but incompatible live donors.

Organ shortage has led to increased utilization of higher risk liver allografts. In kidneys, aggressive center-level use of one type of higher risk graft clustered with aggressive use of other types. In this study, we explored center-level behavior in liver utilization. We aggregated national liver transplant recipient data between 2005 and 2009 to the center-level, assigning each center an aggressiveness score based on relative utilization of higher risk livers. Aggressive centers had significantly more patients reaching high MELDs (RR 2.19, 2.33 and 2.28 for number of patients reaching MELD>20, MELD>25 and MELD>30, p<0.001), a higher organ shortage ratio (RR 1.51, 1.60 and 1.51 for number of patients reaching MELD>20, MELD>25 and MELD>30 divided by number of organs recovered at the OPO, p<0.04), and were clustered within various geographic regions, particularly regions 2, 3 and 9. Median MELD at transplant was similar between aggressive and nonaggressive centers, but average annual transplant volume was significantly higher at aggressive centers (RR 2.27, 95% CI 1.47-3.51, p<0.001). In cluster analysis, there were no obvious phenotypic patterns among centers with intermediate levels of aggressiveness. In conclusion, highwaitlist disease severity, geographic differences in organ availability, and transplant volume are the main factors associated with the aggressive utilization of higher risk livers.