Faculty Bibliography

The Kidney Donor Profile Index (KDPI) has been introduced as an aid to evaluating deceased donor kidney offers, but the relative benefit of high-KDPI kidney transplantation (KT) versus the clinical alternative (remaining on the waitlist until receipt of a lower KDPI kidney) remains unknown. Using time-dependent Cox regression, we evaluated the mortality risk associated with high-KDPI KT (KDPI 71-80, 81-90 or 91-100) versus a conservative, lower KDPI approach (remain on waitlist until receipt of KT with KDPI 0-70, 0-80 or 0-90) in first-time adult registrants, adjusting for candidate characteristics. High-KDPI KT was associated with increased short-term but decreased long-term mortality risk. Recipients of KDPI 71-80 KT, KDPI 81-90 KT and KDPI 91-100 KT reached a "break-even point" of cumulative survival at 7.7, 18.0 and 19.8 months post-KT, respectively, and had a survival benefit thereafter. Cumulative survival at 5 years was better in all three high-KDPI groups than the conservative approach (p < 0.01 for each comparison). Benefit of high-KDPI KT was greatest in patients age >50 years and patients at centers with median wait time ≥33 months. Recipients of high-KDPI KT can enjoy better long-term survival; a high-KDPI score does not automatically constitute a reason to reject a deceased donor kidney.

The field of organ transplantation benefits from large, comprehensive, transplant-specific national data sets available to researchers. In addition to the widely used Organ Procurement and Transplantation Network (OPTN)-based registries (the United Network for Organ Sharing and Scientific Registry of Transplant Recipients data sets) and United States Renal Data System (USRDS) data sets, there are other publicly available national data sets, not specific to transplantation, which have historically been underutilized in the field of transplantation. Of particular interest are the Nationwide Inpatient Sample and State Inpatient Databases, produced by the Agency for Healthcare Research and Quality. The USRDS database provides extensive data relevant to studies of kidney transplantation. Linkage of publicly available data sets to external data sources such as private claims or pharmacy data provides further resources for registry-based research. Although these resources can transcend some limitations of OPTN-based registry data, they come with their own limitations, which must be understood to avoid biased inference. This review discusses different registry-based data sources available in the United States, as well as the proper design and conduct of registry-based research.

BACKGROUND:Racial disparities in health outcomes after living donation have been reported, but generalizability is not known. METHODS:We linked Organ Procurement and Transplantation Network (OPTN) registry data for 4,007 living kidney donors in 1987 to 2008 with Medicare billing claims (2000-2008). Cox regression with left and right censoring was used to estimate the frequencies and relative risks of postdonation medical diagnoses according to race. Patterns were compared with findings from a previous linkage of OPTN donor records and private insurance claims. RESULTS:Among the Medicare-insured donors, 8% were African American and 5.7% were Hispanic. Diagnosis frequencies at 5 years after donation in the Medicare- versus privately insured donors included the following: malignant hypertension, 5.0% versus 0.9%; diabetes, 18.5% versus 4.1%; and chronic kidney disease, 21.8% versus 4.9%. After age and sex adjustment in the Medicare sample, African Americans, as compared with white donors, experienced higher risks of any hypertension diagnosis, including 2.4 times the likelihood of malignant hypertension (adjusted hazard ratio [aHR], 2.35; 95% confidence interval [CI], 1.40-3.93), and more common diabetes (aHR, 1.50; 95% CI, 1.12-2.04), chronic kidney disease (aHR, 1.84; 95% CI, 1.37-2.47), and proteinuria (aHR, 2.44; 95% CI, 1.45-4.11) diagnoses. Relative patterns for privately insured African American versus white donors were similar, including approximately three times the risk of malignant hypertension (aHR, 3.27; 95% CI, 1.82-5.88) and twice the relative risks of chronic kidney disease and proteinuria. CONCLUSIONS:Consistent demonstration of racial variation in postdonation medical conditions regardless of sample/payer source supports the need for continued study of mediators and consequences of outcomes in non-white donors.

Despite improved overall liver transplant outcomes, biliary complications remain a significant cause of morbidity. A national data set linking transplant registry and Medicare claims data for 17,012 liver transplant recipients was used to identify all recipients with a posttransplant biliary diagnosis code within the first 6 months after transplantation. Patients were further categorized as follows: a diagnosis without a procedure, a diagnosis and an associated radiological or endoscopic procedure, or a diagnosis treated with surgery. Overall, 15.0% had a biliary diagnosis, 11.2% required a procedure, and 2.2% had a surgical revision. Factors independently associated with biliary complications included donation after cardiac death (DCD), donor age, recipient age, split grafts, and long cold ischemia times. Graft loss was significantly more common for patients with biliary diagnoses [adjusted hazard ratio (aHR) = 1.89, confidence interval (CI) = 1.63-2.19], interventions (aHR = 2.08, CI = 1.77-2.44), and surgical procedures (aHR = 1.80, CI = 1.31-2.49). Mortality after transplantation was also markedly increased for patients with biliary diagnoses (aHR = 2.18, CI = 1.97-2.40), procedures (aHR = 2.21, CI = 1.99-2.46), and surgeries (aHR = 1.77, CI = 1.41-2.23). In stratified analyses, the impact of early biliary complications was greater for DCD liver recipients, but they remained highly significant for recipients of allografts from brain-dead donors as well. Reducing biliary complications should improve posttransplant survival and reduce graft loss.

OBJECTIVE:To investigate changes in pediatric kidney transplant outcomes over time and potential variations in these changes between the early and late posttransplant periods and across subgroups based on recipient, donor, and transplant characteristics. METHODS:Using multiple logistic regression and multivariable Cox models, graft and patient outcomes were analyzed in 17,446 pediatric kidney-only transplants performed in the United States between 1987 and 2012. RESULTS:Ten-year patient and graft survival rates were 90.5% and 60.2%, respectively, after transplantation in 2001, compared with 77.6% and 46.8% after transplantation in 1987. Primary nonfunction and delayed graft function occurred in 3.3% and 5.3%, respectively, of transplants performed in 2011, compared with 15.4% and 19.7% of those performed in 1987. Adjusted for recipient, donor, and transplant characteristics, these improvements corresponded to a 5% decreased hazard of graft loss, 5% decreased hazard of death, 10% decreased odds of primary nonfunction, and 5% decreased odds of delayed graft function with each more recent year of transplantation. Graft survival improvements were lower in adolescent and female recipients, those receiving pretransplant dialysis, and those with focal segmental glomerulosclerosis. Patient survival improvements were higher in those with elevated peak panel reactive antibody. Both patient and graft survival improvements were most pronounced in the first posttransplant year. CONCLUSIONS:Outcomes after pediatric kidney transplantation have improved dramatically over time for all recipient subgroups, especially for highly sensitized recipients. Most improvement in graft and patient survival has come in the first year after transplantation, highlighting the need for continued progress in long-term outcomes.

OBJECTIVES/OBJECTIVE:To explore whether disparities in age and sex in access to kidney transplantation (KT) originate at the time of prereferral discussions about KT. DESIGN/METHODS:Cross-sectional survey. SETTING/METHODS:Outpatient dialysis centers in Maryland (n = 26). PARTICIPANTS/METHODS:Individuals who had recently initiated hemodialysis treatment (N = 416). MEASUREMENTS/METHODS:Participants reported whether medical professionals (nephrologist, primary medical doctor, dialysis staff) and social group members (significant other, family member, friend) discussed KT with them and, when applicable, rated the tone of discussions. Relative risks were estimated using modified Poisson regression. RESULTS:Participants aged 65 and older were much less likely than those who were younger to have had discussions with medical professionals (44.5% vs 74.8%, P < .001) or social group members (47.3% vs 63.1%, P = .005). Irrespective of sex and independent of race, health-related factors, and dialysis-related characteristics, older adults were more likely not to have had discussions with medical professionals (relative risk (RR) = 1.13, 95% confidence interval (CI) = 1.03-1.24, for each 5-year increase in age through 65; RR = 1.28, 95% CI = 1.14-1.42, for each 5-year increase in age beyond 65). Irrespective of age, women were more likely (RR = 1.45, 95% CI = 1.12-1.89) not to have had discussions with medical professionals. For each 5-year increase in age, men (RR = 1.04, 95% CI = 0.99-1.10) and women (RR = 1.17, 95% CI = 1.10-1.24) were more likely not to have discussions with social group members. Of those who had discussions with medical professionals or social group members, older participants described these discussions as less encouraging (all P < .01). CONCLUSION/CONCLUSIONS:Older adults and women undergoing hemodialysis are less likely than younger adults and men to have discussions about KT as a treatment option, supporting a need for better clinical guidelines and education for these individuals, their social network, and their providers.

Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL-12 production and T-cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV-V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22). Along with a statistically significant reduction in mDC levels, reduced CD8(+) T-cell levels were also demonstrated in the kidney disease groups compared with HC. Reduced PB mDC and monocyte-derived DC (MoDC) IL-12 production was observed after in vitro LPS stimulation in the HD versus HC groups. Finally, ELISpot assays demonstrated less robust CD3(+) INF-γ responses by MoDCs pulsed with CMV pp65 peptide from HD patients compared with HC. PB mDC level deficiency in patients with kidney disease is associated with deficient IL-12 production and T-cell level/function, which may explain the known correlation of CD8(+) T-cell lymphopenia with deficient post-transplant antiviral responses.

Recent allocation policy changes have increased the sharing of deceased donor livers across local boundaries, and sharing even broader than this has been proposed as a remedy for persistent geographic disparities in liver transplantation. It is possible that broader sharing may increase cold ischemia times (CITs) and thus harm recipients. We constructed a detailed model of transport modes (car, helicopter, and fixed-wing aircraft) and transport times between all hospitals, and we investigated the relationship between the transport time and the CIT for deceased donor liver transplants. The median estimated transport time was 2.0 hours for regionally shared livers and 1.0 hour for locally allocated livers. The model-predicted transport mode was flying for 90% of regionally shared livers but for only 22% of locally allocated livers. The median CIT was 7.0 hours for regionally shared livers and 6.0 hours for locally allocated livers. Variation in the transport time accounted for only 14.7% of the variation in the CIT, and the transport time on average composed only 21% of the CIT. In conclusion, nontransport factors play a substantially larger role in the CIT than the transport time. Broader sharing will have only a marginal impact on the CIT but will significantly increase the fraction of transplants that are transported by flying rather than driving.