Faculty Bibliography

Human immunodeficiency virus (HIV) is no longer a contraindication to transplantation. For HIV-infected patients, HIV-infected deceased donors (HIVDD) could attenuate the organ shortage and waitlist mortality. However, this practice would violate United States federal law. The goal of this study was to estimate the potential impact of legalizing transplantation of HIV-infected organs by quantifying the potential pool of HIVDD. Using Nationwide Inpatient Sample (NIS) data, HIV-infected deaths compatible with donation were enumerated. Using HIV Research Network (HIVRN) data, CD4 count, plasma HIV-1 RNA level, AIDS-defining illnesses and causes of death were examined in potential HIVDD. Using UNOS data, evaluated donors who later demonstrated unanticipated HIV infections were studied. From NIS, a yearly average of 534 (range: 481-652) potential HIVDD were identified, with 63 (range: 39-90) kidney-only, 221 (range: 182-255) liver-only and 250 (range: 182-342) multiorgan donors. From HIVRN, a yearly average of 494 (range: 441-533) potential HIVDD were identified. Additionally, a yearly average of 20 (range: 11-34) donors with unanticipated HIV infection were identified from UNOS. Deceased HIV-infected patients represent a potential of approximately 500-600 donors per year for HIV-infected transplant candidates. In the current era of HIV management, a legal ban on the use of these organs seems unwarranted and likely harmful.

The OPTN classifies high infectious risk donors (HRDs) based on criteria originally intended to identify people at risk for HIV infection. These donors are sometimes referred to as 'CDC high risk donors' in reference to the CDC-published guidelines adopted by the OPTN. However, these guidelines are also being used to identify deceased donors at increased risk of window period (WP) hepatitis C virus (HCV) infection, although not designed for this purpose. The actual risk of WP HCV infection in HRDs is unknown. We performed a systematic review of 3476 abstracts and identified 37 eligible estimates of HCV incidence in HRD populations in the United States/Canada. Pooled HCV incidence was derived and used to estimate the risk of WP infection for each HRD category. Risks ranged from 0.26 to 300.6 per 10,000 donors based on WP for ELISA and 0.027 to 32.4 based on nucleic acid testing (NAT). Injection drug users were at highest risk (32.4 per 10,000 donors by NAT WP), followed by commercial sex workers and donors exhibiting high risk sexual behavior (12.3 per 10,000), men who have sex with men (3.5 per 10,000), incarcerated donors (0.8 per 10,000), donors exposed to HIV infected blood (0.4 per 10,000) and hemophiliacs (0.027 per 10,000). NAT reduced WP risk by approximately 10-fold in each category.

The OPTN defines high risk donors (HRDs), colloquially known as 'CDC high risk donors', as those thought to carry an increased risk of HIV window period (WP) infection prior to serologic detectability. However, the true risk of such infection remains unknown. To quantify the risk of WP infection in each HRD behavior category, we performed a systematic review and meta-analysis of studies of HIV prevalence and incidence. Of 3476 abstracts reviewed, 27 eligible studies of HIV infection in HRD populations were identified. Pooled HIV incidence estimates were calculated for each category of HRD behavior and used to calculate the risk of WP HIV infection. Risks ranged from 0.09-12.1 per 10 000 donors based on WP for ELISA and 0.04-4.9 based on nucleic acid testing (NAT), with NAT reducing WP risk by over 50% in each category. Injection drug users had the greatest risk of WP infection (4.9 per 10 000 donors by NAT WP), followed by men who have sex with men (4.2:10 000), commercial sex workers (2.7:10 000), incarcerated donors (0.9:10 000), donors exposed to HIV through blood (0.6:10 000), donors engaging in high-risk sex (0.3:10 000) and hemophiliacs (0.035:10 000). These estimates can help inform patient and provider decision making regarding HRDs.

BACKGROUND: Kidney transplants from pediatric donors after cardiac death (PDCD) have quadrupled in the past 9 years, but little data exist on outcomes using these donors. We hypothesized that pediatric organs might be more sensitive to the pathophysiology of cardiac death. METHODS: We evaluated outcomes and rates of discard of more than 12,000 pediatric kidneys recovered between 2000 and 2009. We compared short- and long-term graft function among adult and pediatric recipients of PDCD kidneys compared with recipients of pediatric kidneys from donors after brain death (PDBD). RESULTS: Overall, 6.3% of pediatric kidneys recovered were PDCD and 93.7% were PDBD. Discard rates were higher for PDCD kidneys (adjusted odds ratio=1.69, 95% confidence interval [CI]=1.31-2.18, P<0.001). Delayed graft function (DGF) was twice as common in recipients of PDCD grafts compared with PDBD (26.2% vs. 13.0%, P<0.001); however, among pediatric recipients, DGF rates were half of those observed in adults, and a statistically significant difference in DGF could not be detected between PDBD and PDCD grafts (6.9% vs. 4.9%, P=0.6). Among all recipients, PDCD kidneys had a greater risk of graft loss compared with PDBD kidneys (adjusted hazard ratio=1.32, 95% CI=1.06-1.65, P=0.01), although among pediatric recipients this increased risk was not statistically significant (adjusted hazard ratio=2.01, 95% CI=0.89-4.54, P=0.1). CONCLUSIONS: The differences in outcomes between adult recipients of PDCD and PDBD kidneys, and the attenuation of these differences among pediatric recipients, should be weighed against risks of prolonged waitlist time in recipients being considered for these grafts.

Optimizing the possibilities for kidney-paired donation (KPD) requires the participation of donor-recipient pairs from wide geographic regions. Initially it was envisaged that donors would travel to the recipient center; however, to minimize barriers to participation and simplify logistics, recent trends have involved transporting the kidneys rather than the donors. The goal of this study was to review outcomes of this practice. KPD programs throughout the United States were directly queried about all transplants involving live donor kidney transport. Early graft function was assessed by urine output in the first 8 h, postoperative serum creatinine trend, and incidence of delayed graft function. Between April 27, 2007 and April 29, 2010, 56 live donor kidneys were transported among 30 transplant centers. Median CIT was 7.2 h (IQR 5.5-9.7, range 2.5-14.5). Early urine output was robust (>100 cc/h) in all but four patients. Creatinine nadir was <2.0 mg/dL in all (including the four with lower urine output) but one patient, occurring at a median of 3 days (IQR 2-5, range 1-49). No patients experienced delayed graft function as defined by the need for dialysis in the first week. Current evidence suggests that live donor kidney transport is safe and feasible.

Incompatibility between the candidate recipient and the prospective donor is a major obstacle to living donor kidney transplant. Kidney paired donation (KPD) can circumvent the incompatibility by matching them to another candidate and living donor for an exchange of transplants such that both transplants are compatible. KPD has faced legal, logistical, and ethical challenges since its inception in the 1980s. Although the full potential of this modality for facilitating transplant for individuals with incompatible donors is unrealized, great strides have been made. In this review article, we detail how several impediments to KPD have been overcome to the benefit of ever greater numbers of patients. Limitations and questions that have been addressed include blood group type O imbalance, reciprocal match requirements, simultaneous donor nephrectomy requirements, combining KPD with desensitization, the role of list-paired donation, geographic barriers, legal barriers, concerns regarding living donor safety, fragmented registries, and inefficient matching algorithms.

OBJECTIVE: On November 13, 2007, the first reported case in 20 years of HIV (human immunodeficiency virus) transmission from a Centers for Disease Control and Prevention high-risk donor (HRD) made national headlines. We sought to characterize change in the practice of transplant surgeons resulting from this rare event. DESIGN: We performed a survey between January 17, 2008, and April 15, 2008, assessing attitudes and practices of transplant surgeons regarding HRDs. Descriptions of changes in practice after the event were categorized, and associations between responses and regional-, center-, and physician-level factors were studied. SETTING: Transplant centers in the United States. PARTICIPANTS: Four hundred twenty-two transplant surgeons in current practice. MAIN OUTCOME MEASURE: Changing practice following the 2007 HIV transmission event. RESULTS: Among surgeons who responded to the survey, 31.6% changed their practice following the event. Also, 41.7% decreased use of HRDs, 34.5% increased emphasis on informed consent, 16.7% increased use of nucleic acid testing, and 6.0% implemented a formal policy. Ranking fear of being sued or hospital pressure as important disincentives to HRD use was associated with more than 2-fold higher odds of changing practice. Ranking medical risks of HIV as an important disincentive was associated with 8.29-fold higher odds of decreasing HRD use. CONCLUSION: The most common responses to this rare event were avoidance (decreased HRD use) and assurance (increased emphasis on informed consent) behaviors rather than patient safety measures (increased use of nucleic acid testing and implementation of formal policies), suggesting that fear of legal or regulatory consequences was the biggest driver of physician decision making and that the current litigious environment is failing to protect patient interests.