Faculty Bibliography

BACKGROUND:Living-donor kidney transplantation (KT) is encouraged for children with end-stage renal disease due to superior long-term graft survival compared with deceased-donor KT. Despite this, there has been a steady decrease in the use of living-donor KT for pediatric recipients. Due to their young age at transplantation, most pediatric recipients eventually require retransplantation, and the optimal order of donor type is not clear. METHODS:Using the Scientific Registry of Transplant Recipients, we analyzed first and second graft survival among 14,799 pediatric (<18 years old) recipients undergoing KT between 1987 and 2010. RESULTS:Living-donor grafts had longer survival compared with deceased-donor grafts, similarly among both first (adjusted hazard ratio [aHR], 0.78; 95% confidence interval [CI], 0.73-0.84; P<0.001) and second (aHR, 0.74; 95% CI, 0.64-0.84; P<0.001) transplants. Living-donor second grafts had longer survival compared with deceased-donor second grafts, similarly after living-donor (aHR, 0.68; 95% CI, 0.56-0.83; P<0.001) and deceased-donor (aHR, 0.77; 95% CI, 0.63-0.95; P=0.02) first transplants. Cumulative graft life of two transplants was similar regardless of the order of deceased-donor and living-donor transplantation. CONCLUSIONS:Deceased-donor KT in pediatric recipients followed by living-donor retransplantation does not negatively impact the living-donor graft survival advantage and provides similar cumulative graft life compared with living-donor KT followed by deceased-donor retransplantation. Clinical decision-making for pediatric patients with healthy, willing living donors should consider these findings in addition to the risk of sensitization, aging of the living donor, and deceased-donor waiting times.

BACKGROUND AND OBJECTIVE/OBJECTIVE:The risk of graft loss after pediatric kidney transplantation increases during late adolescence and early adulthood, but the extent to which this phenomenon affects all recipients is unknown. This study explored interactions between recipient factors and this high-risk age window, searching for a recipient phenotype that may be less susceptible during this detrimental age interval. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:With use of Scientific Registry of Transplant Recipients data from 1987 to 2010, risk of graft loss across recipient age was quantified using a multivariable piecewise-constant hazard rate model with time-varying coefficients for recipient risk factors. RESULTS:Among 16,266 recipients, graft loss during ages ≥17 and <24 years was greater than that for both 3-17 years (adjusted hazard ratio [aHR], 1.61; P<0.001) and ≥24 years (aHR, 1.28; P<0.001). This finding was consistent across age at transplantation, sex, race, cause of renal disease, insurance type, pretransplant dialysis history, previous transplant, peak panel-reactive antibody (PRA), and type of induction immunosuppression. The high-risk window was seen in both living-donor and deceased-donor transplant recipients, at all levels of HLA mismatch, regardless of centers' pediatric transplant volume, and consistently over time. The relationship between graft loss risk and donor type, PRA, transplant history, insurance type, and cause of renal disease was diminished upon entry into the high-risk window. CONCLUSIONS:No recipient subgroups are exempt from the dramatic increase in graft loss during late adolescence and early adulthood, a high-risk window that modifies the relationship between typical recipient risk factors and graft loss.

BACKGROUND/PURPOSE/OBJECTIVE:Living donor kidney transplantation is encouraged for children with end-stage renal disease given the superior survival of living donor grafts, but pediatric candidates are also given preference for kidneys from younger deceased donors. METHODS:Death-censored graft survival of pediatric kidney-only transplants performed in the U.S. between 1987-2012 was compared across living related (LRRT) (n=7741), living unrelated (LURT) (n=618), and deceased donor renal transplants (DDRT) (n=8945) using Kaplan-Meier analysis, multivariable Cox proportional hazards models, and matched controls analysis. RESULTS:As expected, HLA mismatch was greater among LURT compared to LRRT (p<0.001). Unadjusted graft survival was lower, particularly long-term, for LURT compared to LRRT (p=0.009). However, LURT graft survival was still superior to DDRT graft survival, even when compared only to deceased donors under age 35 (p=0.002). The difference in graft survival between LURT and LRRT was not seen when adjusting for HLA mismatch, year of transplantation, and donor and recipient characteristics using a Cox model (aHR=1.04, 95% CI: 0.87-1.24, p=0.7) or matched controls (HR=1.02, 95% CI: 0.82-1.27, p=0.9). CONCLUSION/CONCLUSIONS:Survival of LURT grafts is superior to grafts from younger deceased donors and equivalent to LRRT grafts when adjusting for other factors, most notably differences in HLA mismatch.

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.