Faculty Bibliography

Deceased donors are labeled increased risk for disease transmission (IRD) if they meet certain criteria. New PHS guidelines were recently implemented; the impact of these changes remains unknown. We aimed to quantify the impact of the new guidelines on the proportion of deceased donors labeled IRD, as well as demographic and clinical characteristics. We used Poisson regression with an interaction term for era (new vs. old guidelines) to quantify changes. Under the new guidelines, 19.5% donors were labeled IRD, compared to 10.4%, 12.2%, and 12.3% in the 3 most recent years under the old guidelines (IRR = 1.45, p < 0.001). Increases were consistent across OPOs: 44/59 had an increase in the percent of donors labeled IRD, and 14 OPOs labeled 25% of their donors IRD under the new guidelines (vs. 5 OPOs under the old). African-Americans were 52% more likely to be labeled IRD under the new guidelines (RR = 1.52, p = 0.01). There has been a substantial increase in donors labeled IRD under the new PHS guidelines; it is important to understand the mechanism and consequences to ensure an optimal balance of patient safety and organ utilization is achieved.

We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01-4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.

In June 2013, a change to the liver waitlist priority algorithm was implemented. Under Share 35, regional candidates with MELD ≥ 35 receive higher priority than local candidates with MELD < 35. We compared liver distribution and mortality in the first 12 months of Share 35 to an equivalent time period before. Under Share 35, new listings with MELD ≥ 35 increased slightly from 752 (9.2% of listings) to 820 (9.7%, p = 0.3), but the proportion of deceased-donor liver transplants (DDLTs) allocated to recipients with MELD ≥ 35 increased from 23.1% to 30.1% (p < 0.001). The proportion of regional shares increased from 18.9% to 30.4% (p < 0.001). Sharing of exports was less clustered among a handful of centers (Gini coefficient decreased from 0.49 to 0.34), but there was no evidence of change in CIT (p = 0.8). Total adult DDLT volume increased from 4133 to 4369, and adjusted odds of discard decreased by 14% (p = 0.03). Waitlist mortality decreased by 30% among patients with baseline MELD > 30 (SHR = 0.70, p < 0.001) with no change for patients with lower baseline MELD (p = 0.9). Posttransplant length-of-stay (p = 0.2) and posttransplant mortality (p = 0.9) remained unchanged. In the first 12 months, Share 35 was associated with more transplants, fewer discards, and lower waitlist mortality, but not at the expense of CIT or early posttransplant outcomes.

BACKGROUND:Induction immunosuppression is a mainstay of rejection prevention after transplantation. Studies have suggested a connection between antibody induction agents and cancer development, potentially limiting important immunosuppression protocols. METHODS:We used a linkage of U.S. transplantation data and cancer registries to explore the relationship between induction and cancer after transplantation. A total of 111,857 kidney recipients (1987-2009) in the Transplant Cancer Match Study, which links the Scientific Registry for Transplant Recipients and U.S. Cancer Registries, were included. Poisson regression models were used to estimate adjusted incidence rate ratios (aIRR) of non-Hodgkin lymphoma (NHL) and other cancers with increased incidence after transplantation (lung, colorectal, kidney, and thyroid cancers, plus melanoma). RESULTS:Two thousand seven hundred sixty-three cancers of interest were identified. Muromonab-CD3 was associated with increased NHL (aIRR, 1.37; 95% CI, 1.06-1.76). Alemtuzumab was associated with increased NHL (aIRR, 1.79; 95% CI, 1.02-3.14), colorectal cancer (aIRR, 2.46; 95% CI, 1.03-5.91), and thyroid cancer (aIRR, 3.37; 95% CI, 1.55-7.33). Polyclonal induction was associated with increased melanoma (aIRR, 1.50; 95% CI, 1.06-2.14). CONCLUSION/CONCLUSIONS:Our findings highlight the relative safety with regard to cancer risk of the most common induction therapies, the need for surveillance of patients treated with alemtuzumab, and the possible role for increased melanoma screening for those patients treated with polyclonal anti-T-cell induction.

BACKGROUND:Young women wishing to become living kidney donors frequently ask whether nephrectomy will affect their future pregnancies. METHODS:We conducted a retrospective cohort study of living kidney donors involving 85 women (131 pregnancies after cohort entry) who were matched in a 1:6 ratio with 510 healthy nondonors from the general population (788 pregnancies after cohort entry). Kidney donations occurred between 1992 and 2009 in Ontario, Canada, with follow-up through linked health care databases until March 2013. Donors and nondonors were matched with respect to age, year of cohort entry, residency (urban or rural), income, number of pregnancies before cohort entry, and the time to the first pregnancy after cohort entry. The primary outcome was a hospital diagnosis of gestational hypertension or preeclampsia. Secondary outcomes were each component of the primary outcome examined separately and other maternal and fetal outcomes. RESULTS:Gestational hypertension or preeclampsia was more common among living kidney donors than among nondonors (occurring in 15 of 131 pregnancies [11%] vs. 38 of 788 pregnancies [5%]; odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P=0.01). Each component of the primary outcome was also more common among donors (odds ratio, 2.5 for gestational hypertension and 2.4 for preeclampsia). There were no significant differences between donors and nondonors with respect to rates of preterm birth (8% and 7%, respectively) or low birth weight (6% and 4%, respectively). There were no reports of maternal death, stillbirth, or neonatal death among the donors. Most women had uncomplicated pregnancies after donation. CONCLUSIONS:Gestational hypertension or preeclampsia was more likely to be diagnosed in kidney donors than in matched nondonors with similar indicators of baseline health. (Funded by the Canadian Institutes of Health Research and others.).

Whether the liver allocation system shifts organs from better performing organ procurement organizations (OPOs) to poorer performing OPOs has been debated for many years. Models of OPO performance from the Scientific Registry of Transplant Recipients make it possible to study this question in a data-driven manner. We investigated whether each OPO's net liver import was correlated with 2 performance metrics [observed to expected (O:E) liver yield and liver donor conversion ratio] as well as 2 alternative explanations [eligible deaths and incident listings above a Model for End-Stage Liver Disease (MELD) score of 15]. We found no evidence to support the hypothesis that the allocation system transfers livers from better performing OPOs to centers with poorer performing OPOs. Also, having fewer eligible deaths was not associated with a net import. However, having more incident listings was strongly correlated with the net import, both before and after Share 35. Most importantly, the magnitude of the variation in OPO performance was much lower than the variation in demand: although the poorest performing OPOs differed from the best ones by less than 2-fold in the O:E liver yield, incident listings above a MELD score of 15 varied nearly 14-fold. Although it is imperative that all OPOs achieve the best possible results, the flow of livers is not explained by OPO performance metrics, and instead, it appears to be strongly related to differences in demand.

BACKGROUND AND OBJECTIVES/OBJECTIVE:African Americans are disproportionately affected by ESRD, but few receive a living donor kidney transplant. Surveys assessing attitudes toward donation have shown that African Americans are less likely to express a willingness to donate their own organs. Studies aimed at understanding factors that may facilitate the willingness of African Americans to become organ donors are needed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:A novel formative research method was used (the nominal group technique) to identify and prioritize strategies for facilitating increases in organ donation among church-attending African Americans. Four nominal group technique panel interviews were convened (three community and one clergy). Each community panel represented a distinct local church; the clergy panel represented five distinct faith-based denominations. Before nominal group technique interviews, participants completed a questionnaire that assessed willingness to become a donor; 28 African-American adults (≥19 years old) participated in the study. RESULTS:In total, 66.7% of participants identified knowledge- or education-related strategies as most important strategies in facilitating willingness to become an organ donor, a view that was even more pronounced among clergy. Three of four nominal group technique panels rated a knowledge-based strategy as the most important and included strategies, such as information on donor involvement and donation-related risks; 29.6% of participants indicated that they disagreed with deceased donation, and 37% of participants disagreed with living donation. Community participants' reservations about becoming an organ donor were similar for living (38.1%) and deceased (33.4%) donation; in contrast, clergy participants were more likely to express reservations about living donation (33.3% versus 16.7%). CONCLUSIONS:These data indicate a greater opposition to living donation compared with donation after one's death among African Americans and suggest that improving knowledge about organ donation, particularly with regard to donor involvement and donation-related risks, may facilitate increases in organ donation. Existing educational campaigns may fall short of meeting information needs of African Americans.

IMPORTANCE/OBJECTIVE:Based on evidence of survival benefit when initiating hemodialysis (HD) via arteriovenous fistula (AVF) or arteriovenous graft (AVG) vs hemodialysis catheter (HC), the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative published practice guidelines in 1997 recommending 50% or greater AVF rates in incident HD patients. A decade after, lapses exist and the impact on HD outcomes is uncertain. OBJECTIVE:To assess the achievement of the practice goals for incident vascular access and the effects on HD outcomes. DESIGN, SETTING, AND PARTICIPANTS/METHODS:This retrospective cohort study was conducted using the US Renal Data System. All patients with end-stage renal disease in the United States without prior renal replacement therapy who had incident vascular access for HD created between January 1, 2006, and December 31, 2010 (N = 510 000) were included. MAIN OUTCOMES AND MEASURES/METHODS:Incident vascular access use rates and mortality. Relative mortality was quantified using multivariable Cox proportional hazard models. Coarsened exact matching and propensity score-matching techniques were used to better account for confounding by indication. RESULTS:Of 510 000 patients included in this study, 82.6% initiated HD via HC, 14.0% via AVF, and 3.4% via AVG. Arteriovenous fistula use increased only minimally, from 12.2% in 2006 to 15.0% in 2010. Patients initiating HD with AVF had 35% lower mortality than those with HC (adjusted hazard ratio, 0.65; 95% CI, 0.64-0.66; P < .001). Those initiating HD with AVF had 23% lower mortality than those initiating with an HC while awaiting maturation of an AVF (adjusted hazard ratio, 0.77; 95% CI, 0.76-0.79; P < .001). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Current incident AVF practice falls exceedingly short years after recommendations were made in 1997. The impact of this shortcoming on mortality for patients with end-stage renal disease is enormous. Functioning permanent access at initiation of HD confers lower mortality even compared with patients temporized with an HC while awaiting maturation of permanent access. A change of current policies and structured multidisciplinary efforts are required to establish matured fistulae prior to HD to ameliorate this deficit in delivering care.