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.

BACKGROUND: More than 25% of pediatric kidney transplants are lost within 7 years, necessitating dialysis or retransplantation. Retransplantation practices and the outcomes of repeat transplantations, particularly among those with early graft loss, are not clear. METHODS: We examined retransplantation practice patterns and outcomes in 14,799 pediatric (ages <18 years) patients between 1987 and 2010. Death-censored graft survival was analyzed using extended Cox models and retransplantation using competing risks regression. RESULTS: After the first graft failure, 50.4% underwent retransplantation and 12.1% died within 5 years; after the second graft failure, 36.1% underwent retransplantation and 15.4% died within 5 years. Prior preemptive transplantation and graft loss after 5 years were associated with increased rates of retransplantation. Graft loss before 5 years, older age, non-Caucasian race, public insurance, and increased panel-reactive antibody were associated with decreased rates of retransplantation. First transplants had lower risk of graft loss compared with second (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.64-0.80; P<0.001), third (aHR, 0.62; 95% CI, 0.49-0.78; P<0.001), and fourth (aHR, 0.44; 95% CI, 0.24-0.78; P=0.005) transplants. However, among patients receiving two or more transplants (conditioned on having lost a first transplant), second graft median survival was 8.5 years despite a median survival of 4.5 years for the first transplant. Among patients receiving three or more transplants, third graft median survival was 7.7 years despite median survivals of 2.1 and 3.1 years for the first and second transplants. CONCLUSIONS: Among pediatric kidney transplant recipients who experience graft loss, racial and socioeconomic disparities exist with regard to retransplantation, and excellent graft survival can be achieved with retransplantation despite poor survival of previous grafts.

BACKGROUND:The clinical characteristics and outcomes of patients with glycogen storage disease (GSD) who undergo liver transplantation (LT) have not been well defined. In this study, our objective was to determine the outcome of LT in patients with GSD and compare it with a comparable group of patients without GSD (matched controls). METHODS:UNOS data from 1986 to 2007 were used for this study. For each GSD patient (n = 95; men 62%) who was transplanted, three patients (n = 285, men 60%) without GSD (case controls) matched for age ± five yr, year of transplantation and donor risk index (DRI) ± 0.2 were identified from the UNOS database in a random manner. Unadjusted patient survival was determined by Kaplan-Meier survival analysis and significance determined by log-rank test. RESULTS:The mean age of the group was 17.9 yr. GSD patients had lower BMI (22 vs. 24, p = 0.002), lower serum bilirubin (2.7 vs. 13.5 mg/dL, p < 0.0001), higher serum albumin (3.7 vs. 3.1 g/dL, p < 0.0001), and higher wait-list time (239 vs. 74 d, p < 0.0001) compared to case controls. Recipient age and DRI were similar between the groups. Tumors were more common in GSD group (13.7% vs. 5%). Patient survival was significantly better (p = 0.024) in GSD group at one, five, and 10 yr (82%, 76%, and 64%) than non-GSD (73%, 65%, and 59%) group. CONCLUSIONS:In this matched-control study, patients who underwent LT for GSD had a better long-term survival than a comparable group of patients without GSD.

Expanding the pool of available deceased donor kidneys is critical for improving the outcomes of prospective and current renal transplant candidates. A number of interventions have been proposed that may increase the pool of donors in the US. However, these interventions have variable levels of empirical evidence supporting their potential beneficial impact. Proposed interventions include the instigation of policies for presumed donor consent, the expansion of donor registration, increased quality oversight of transplant providers, financial incentives for donors, increased reimbursement for higher risk donors, alterations in organ allocation policies and distribution, and the selective use of donors with potential or known risk for disease transmission. Many of these interventions have contentious elements that may have delayed or impeded their implementation; however, these options should be considered in the context of the diminishing prognoses for prospective transplant patients, given the increasing scarcity of donor organs relative to the population need. In this Review, we outline the proposed interventions and briefly discuss salient issues that characterize the debates concerning their implementation and effectiveness. Ultimately, any intervention must be based on the best evidence available, with consideration of numerous stakeholders and in conjunction with a careful evaluation of long-term and potential unintended consequences.