Faculty Bibliography

BACKGROUND: Human leukocyte antigen (HLA) sensitization presents a major obstacle for patients awaiting renal transplantation. HLA antibody reduction and favorable transplantation rates have been reported after treatment with high-dose intravenous immunoglobulin (IVIg). METHODS: We enrolled 27 patients whose median flow cytometric calculated panel reactive antibody (CPRA) was 100% and mean wait-list time exceeded 4 years in a protocol whereby high-dose IVIg was administered, HLA antibody profiles of sera obtained before and after treatment were characterized, and cross-match tests were performed with all blood group identical kidney offers. RESULTS: Whereas 12.8% of a similarly sensitized historic control cohort underwent transplantation in the course of a year, 41% of the IVIg-treated group underwent transplantation during the study period. Surprisingly, HLA antibody profiles, measured by CPRA, showed no significant change in response to IVIg treatment. In fact, retrospective cross-match testing using pretreatment sera of those receiving deceased-donor allografts showed that all patients would have been eligible for transplantation with their respective donors before IVIg infusions. CONCLUSIONS: This study does not corroborate previous reports of CPRA reduction leading to increased deceased-donor transplantation rates in broadly sensitized patients undergoing desensitization with high-dose IVIg. The increased rate of transplantation relative to historic controls is not related to improved cross-match eligibility and likely resulted from frequent crossmatching using a cytotoxic strength threshold, improved medical readiness for transplantation, and newly recognized options for live-donor transplantation, all of which could have been achieved without IVIg treatment.

Kidney paired donation represented 10% of living kidney donation in the United States in 2011. National registries around the world and several separate registries in the United States arrange paired donations, although with significant variations in their practices. Concerns about ethical considerations, clinical advisability, and the quantitative effectiveness of these approaches in paired donation result in these variations. For instance, although donor travel can be burdensome and might discourage paired donation, it was nearly universal until convincing analysis showed that living donor kidneys can sustain many hours of cold ischemia time without adverse consequences. Opinions also differ about whether the last donor in a chain of paired donation transplants initiated by a nondirected donor should donate immediately to someone on the deceased donor wait-list (a domino or closed chain) or should be asked to wait some length of time and donate to start another sequence of paired donations later (an open chain); some argue that asking the donor to donate later may be coercive, and others focus on balancing the probability that the waiting donor withdraws versus the number of additional transplants if the chain can be continued. Other controversies in paired donation include simultaneous versus nonsimultaneous donor operations, whether to enroll compatible pairs, and interactions with desensitization protocols. Efforts to expand public awareness of and participation in paired donation are needed to generate more transplant opportunities.

BACKGROUND: Lack of education and reluctance to initiate a conversation about live donor kidney transplantation is a common barrier to finding a donor. Although transplant candidates are often hesitant to discuss their illness, friends or family members are often eager to spread awareness and are empowered by advocating for the candidates. We hypothesized that separating the advocate from the patient is important in identifying live donors. METHODS: We developed an intervention to train a live donor champion (LDC; a friend, family member, or community member willing to advocate for the candidate) for this advocacy role. We compared outcomes of 15 adult kidney transplant candidates who had no prospective donors and underwent the LDC intervention with 15 matched controls from our waiting list. RESULTS: Comfort in initiating a conversation about transplantation increased over time for LDCs. Twenty-five potential donors contacted our center on behalf of LDC participants; four participants achieved live donor kidney transplantation and three additional participants have donors in evaluation, compared with zero among matched controls (P < 0.001). CONCLUSIONS: Transplant candidates are ill equipped to seek live donors; by separating the advocate from the patient, understandable concerns about initiating conversations are reduced.

BACKGROUND: On average, African Americans attain living donor kidney transplantation (LDKT) at decreased rates compared with their non-African American counterparts. However, center-level variations in this disparity or the role of center-level factors is unknown. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 247,707 adults registered for first-time kidney transplants from 1995-2007 as reported by the Scientific Registry of Transplant Recipients. PREDICTORS: Patient-level factors (age, sex, body mass index, insurance status, education, blood type, and panel-reactive antibody level) were adjusted for in all models. The association of center-level characteristics (number of candidates, transplant volume, LDKT volume, median time to transplant, percentage of African American candidates, percentage of prelisted candidates, and percentage of LDKT) and degree of racial disparity in LDKT was quantified. OUTCOMES: Hierarchical multivariate logistic regression models were used to derive center-specific estimates of LDKT attainment in African American versus non-African American candidates. RESULTS: Racial parity was not seen at any of the 275 transplant centers in the United States. At centers with the least racial disparity, African Americans had 35% lower odds of receiving LDKT; at centers with the most disparity, African Americans had 76% lower odds. Higher percentages of African American candidates (interaction term, 0.86; P = 0.03) and prelisted candidates (interaction term, 0.80; P = 0.001) at a given center were associated with increased racial disparity at that center. Higher rates of LDKT (interaction term, 1.25; P < 0.001) were associated with less racial disparity. LIMITATIONS: Some patient-level factors are not captured, including a given patient's pool of potential donors. Geographic disparities in deceased donor availability might affect LDKT rates. Center-level policies and practices are not captured. CONCLUSIONS: Racial disparity in attainment of LDKT exists at every transplant center in the country. Centers with higher rates of LDKT attainment for all races had less disparity; these high-performing centers might provide insights into policies that might help address this disparity.

BACKGROUND: ABO incompatible (ABOi) kidney transplantation is an important modality to facilitate living donor transplant for incompatible pairs. To date, reports of the outcomes from this practice in the United States have been limited to single-center studies. METHODS: Using the Scientific Registry of Transplant Recipients, we identified 738 patients who underwent live-donor ABOi kidney transplantation between January 1, 1995, and March 31, 2010. These were compared with matched controls that underwent ABO compatible live-donor kidney transplantation. Subgroup analyses among ABOi recipients were performed according to donor blood type, recipient blood type, and transplant center ABOi volume. RESULTS: When compared with ABO compatible-matched controls, long-term patient survival of ABOi recipients was not significantly different between the cohorts (P=0.2). However, graft loss was significantly higher, particularly in the first 14 days posttransplant (subhazard ratio, 2.34; 95% confidence interval, 1.43-3.84; P=0.001), with little to no difference beyond day 14 (subhazard ratio, 1.28; 95% confidence interval, 0.99-1.54; P=0.058). In subgroup analyses among ABOi recipients, no differences in survival were seen by donor blood type, recipient blood type, or transplant center ABOi volume. CONCLUSIONS: These results support the use and dissemination of ABOi transplantation when a compatible live donor is not available, but caution that the highest period of risk is immediately posttransplant.

INTRODUCTION: Deceased donors are considered high infectious risk donors (IRDs) based on criteria thought to be associated with risk of HIV transmission. Significant variation exists in provider willingness to utilize IRD kidneys. Little is known about how patients view these organs. Our aim was to explore patient attitudes toward IRDs and IRD kidney transplantation. METHODS: Patients were recruited from a single-center deceased donor waitlist. Focus groups stratified by age and race were conducted to ascertain patient attitudes toward IRD kidney transplantation. Transcripts were examined using standard qualitative methods. RESULTS: Patients considered IRD kidneys most appropriate for patients at high risk of death or with poor quality of life on dialysis. Patients felt unprepared to receive organ offers, especially from IRDs. They desired information about IRD behaviors, kidney quality, and probability of undetected infection. Patients weighed the opinion of their nephrologist most heavily when deciding about organ offers. A brief education session about donor screening resulted in increased willingness to consider IRD kidneys. CONCLUSIONS: Lack of preparedness contributes to patient apprehension toward IRD organs. Ongoing transplant education seems necessary. The non-transplant nephrologist seems to be the most trusted source of information.

The ability to predict outcomes following a kidney transplant is limited by the complex physiologic decline of kidney failure, a latent factor that is difficult to capture using conventional comorbidity assessment. The frailty phenotype is a recently described inflammatory state of increased vulnerability to stressors resulting from decreased physiologic reserve and dysregulation of multiple physiologic systems. We hypothesized that frailty would be associated with delayed graft function, based on putative associations between inflammatory cytokines and graft dysfunction. We prospectively measured frailty in 183 kidney transplant recipients between December 2008 and April 2010. Independent associations between frailty and delayed graft function were analyzed using modified Poisson regression. Preoperative frailty was independently associated with a 1.94-fold increased risk for delayed graft function (95% CI, 1.13-3.36; P = .02). The assessment of frailty may provide further insights into the pathophysiology of allograft dysfunction and may improve our ability to preoperatively risk-stratify kidney transplant recipients.

BACKGROUND & AIMS: We sought to estimate the risk of perioperative mortality or acute liver failure for live liver donors in the United States and avoid selection or ascertainment biases and sample size limitations. METHODS: We followed up 4111 live liver donors in the United States between April 1994 and March 2011 for a mean of 7.6 years; deaths were determined from the Social Security Death Master File. Survival data were compared with those from live kidney donors and healthy participants of the National Health and Nutrition Examination Survey (NHANES) III. RESULTS: Seven donors had early deaths (1.7 per 1000; 95% confidence interval [CI], 0.7-3.5); risk of death did not vary with age of the liver recipient (1.7 per 1000 for adults vs 1.6 per 1000 for pediatric recipients; P = .9) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 1.5 per 1000 for right lobe; P = .8). There were 11 catastrophic events (early deaths or acute liver failures; 2.9 per 1000; 95% CI, 1.5-5.1); similarly, risk did not vary with recipient age (3.1 per 1000 adult vs 1.6 per 1000 pediatric; P = .4) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 3.3 per 1000 for right lobe; P = .9). Long-term mortality of live liver donors was comparable to that of live kidney donors and NHANES participants (1.2%, 1.2%, and 1.4% at 11 years, respectively; P = .9). CONCLUSIONS: The risk of early death among live liver donors in the United States is 1.7 per 1000 donors. Mortality of live liver donors does not differ from that of healthy, matched individuals over a mean of 7.6 years.

OBJECTIVES: To develop a prediction model for kidney transplantation (KT) outcomes specific to older adults with end-stage renal disease (ESRD) and to use this model to estimate the number of excellent older KT candidates who lack access to KT. DESIGN: Secondary analysis of data collected by the United Network for Organ Sharing and U.S. Renal Disease System. SETTING: Retrospective analysis of national registry data. PARTICIPANTS: Model development: Medicare-primary older recipients (aged >/= 65) of a first KT between 1999 and 2006 (N = 6,988). Model application: incident Medicare-primary older adults with ESRD between 1999 and 2006 without an absolute or relative contraindication to transplantation (N = 128,850). MEASUREMENTS: Comorbid conditions were extracted from U.S. Renal Disease System Form 2728 data and Medicare claims. RESULTS: The prediction model used 19 variables to estimate post-KT outcome and showed good calibration (Hosmer-Lemeshow P = .44) and better prediction than previous population-average models (P < .001). Application of the model to the population with incident ESRD identified 11,756 excellent older transplant candidates (defined as >87% predicted 3-year post-KT survival, corresponding to the top 20% of transplanted older adults used in model development), of whom 76.3% (n = 8,966) lacked access. It was estimated that 11% of these candidates would have identified a suitable live donor had they been referred for KT. CONCLUSION: A risk-prediction model specific to older adults can identify excellent KT candidates. Appropriate referral could result in significantly greater rates of KT in older adults.