Faculty Bibliography

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.

Maximizing deceased donation rates can decrease the organ shortage. Non-transplant physicians play a critical role in facilitating conversion of potential deceased donors to actual donors, but studies suggest that physicians lack knowledge about the organ donation process. As residency and fellowship are often the last opportunities for formal medical training, we hypothesized that deficiencies in knowledge might originate in residency and fellowship. We conducted a cross-sectional survey to assess knowledge about organ donation, experience in donor conversion, and opinions of the process among residents and fellows after their intensive care unit rotations at the Johns Hopkins Hospital. Of 40 participants, 50% had previously facilitated donor conversion, 25% were familiar with the guidelines of the organ procurement organization (OPO), and 10% had received formal instruction from the OPO. The median score on the knowledge assessment was five of 10; higher knowledge score was not associated with level of medical training, prior training in or experience with donor conversion, or with favorable opinions about the OPO. We identified a pervasive deficit in knowledge among residents and fellows at an academic medical center with an active transplant program that may help explain attending-level deficits in knowledge about the organ donation process.

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.

BACKGROUND: The correlation between histopathologic phenotypes and allograft outcomes among patients desensitized for donor-specific antibody (HLA-incompatible) is unknown. METHODS: We analyzed 1-year biopsies from desensitized recipients transplanted between 1999 and 2010 and estimated graft survival for each histologic phenotype identified. Median time posttransplant for the 1-year biopsy was 367 days (interquartile range 357-388 days) and median follow-up of all patients post-1-year biopsy was 42 months (interquartile range 19.5-65 months). RESULTS: Transplant glomerulopathy was present in 25.0% of biopsies and resulted in worse graft survival (66.7% vs. 96.7%, P<0.001). C4d positivity and transplant glomerulopathy together portended exceptionally poor graft survival (33.3% vs. 97.2%, P<0.001). Microcirculation inflammation was prevalent, with glomerulitis and peritubular capillaritis found in 60.0% and 47.6% of 1-year biopsies, respectively. Glomerulitis was associated with worse graft survival (82.1% vs. 98.1%, P=0.004), whereas capillaritis was not (88.1% vs. 97.7% respectively, P=0.091). Among C4d-negative HLA-incompatible recipients (82.6% of biopsies), no difference in graft survival was observed between patients with or without microcirculation inflammation in contrast to previous reports by other investigators. Patients who had no C4d deposition, transplant glomerulopathy, or microcirculation inflammation had a 100.0% graft survival. On Cox regression analysis, no independent histopathological parameter was associated with graft survival. CONCLUSIONS: We have identified several histopathologic phenotypes in HLA-incompatible kidney recipients that correlate with allograft outcomes. Characterization of these phenotypes is the first step towards better understanding the pathophysiologic basis of chronic antibody-mediated allograft injury and individualizing therapeutic intervention.

Current studies of complications following donor hepatectomy may not be generalizable to all hospitals performing this procedure. To address this, live liver donors were identified in the Nationwide Inpatient Sample (2000-2008). Complications after donor hepatectomy were categorized using International Classification of Diseases, Ninth Revision codes and risk factors for complications were tested using logistic regression. Negative binomial regression models were used to estimate the increase in length of stay and hospital charge associated with complications. Among 555 donors (representing 2783 donors nationwide), 23% had 1 or more complications and 5% had a major complication. The most common complications were ileus (27%) and atelectasis (26%). No patient or hospital factors were associated with complications. Having any complication was associated with increased length of stay (incidence rate ratio, 1.36; 95% CI, 1.16-1.58; P < .001) and hospital charge (incidence rate ratio, 1.25; 95% CI, 1.09-1.44; P = .002). Approximately 25% of liver donors have complications immediately postoperatively but most are minor, lending support to current practices in live liver donation and donor selection.

BACKGROUND: Kidney transplantation (KT) is the treatment for end-stage renal disease in appropriate HIV-positive individuals. However, acute rejection (AR) rates are over twice those of HIV-negative recipients. METHODS: To better understand optimal immunosuppression for HIV-positive KT recipients, we studied associations between immunosuppression regimen, AR at 1 year, and survival in 516 HIV-positive and 93,027 HIV-negative adult kidney-only recipients using Scientific Registry of Transplant Recipients data from 2003 to 2011. RESULTS: Consistent with previous reports, HIV-positive patients had twofold higher risk of AR (adjusted relative risk [aRR], 1.77; 95% confidence interval [CI], 1.45-2.2; P<0.001) than their HIV-negative counterparts as well as a higher risk of graft loss (adjusted hazard ratio, 1.51; 95% CI, 1.18-1.94; P=0.001), but these differences were not seen among patients receiving antithymocyte globulin (ATG) induction (aRR for AR, 1.16; 95% CI, 0.41-3.35, P=0.77; adjusted hazard ratio for graft loss, 1.54; 95% CI, 0.73-3.25; P=0.26). Furthermore, HIV-positive patients receiving ATG induction had a 2.6-fold lower risk of AR (aRR, 0.39; 95% CI, 0.18-0.87; P=0.02) than those receiving no antibody induction. Conversely, HIV-positive patients receiving sirolimus-based therapy had a 2.2-fold higher risk of AR (aRR, 2.15; 95% CI, 1.20-3.86; P=0.01) than those receiving calcineurin inhibitor-based regimens. CONCLUSION: These findings support a role for ATG induction, and caution against the use of sirolimus-based maintenance therapy, in HIV-positive individuals undergoing KT.

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.