Faculty Bibliography

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

BACKGROUND:In order to counter the lack of sufficient kidney donors, there has been interest in expanding the utilization of organs from increased infectious-risk donors. Negative nucleic acid testing of increased infectious-risk organs has been shown to increase their use as compared to only enzyme-linked immunosorbent assay negativity. However, it is not known how the expanded use of nucleic acid testing on a national scale might affect total donor utilization. OBJECTIVE:The objective of this paper was to determine if a national screening policy requiring the use of nucleic acid testing in both increased infectious-risk and non-increased infectious-risk renal transplant donors would increase the donor organ pool. METHODS:This study used decision-tree analysis to determine the cost-effectiveness of four US national screening policies based on an increasingly expansive use of nucleic acid testing for increased infectious-risk and non-increased infectious-risk kidneys. Parameters were taken from the literature. All costs were reported in 2020 US dollars using a Medicare payer perspective and a life-time horizon. RESULTS:The use of nucleic acid screening solely for increased infectious-risk organs was the dominant strategy. Our results were robust to deterministic and probabilistic sensitivity analyses. One of the main driving factors of cost-effectiveness was the false-positive rate of nucleic acid testing. CONCLUSION:Before implementing nucleic acid screening outside of increased infectious-risk organs, its false-positivity rate should be directly studied to ensure that its use does not detrimentally affect transplantation numbers, quality-adjusted life-years, and costs.

COVID-19 has profoundly affected the American health care system; its effect on the liver transplant (LT) waitlist based on COVID-19 incidence has not been characterized. Using SRTR data, we compared observed LT waitlist registrations, waitlist mortality, deceased donor LTs (DDLT), and living donor LTs (LDLT) 3/15/2020-8/31/2020 to expected values based on historical trends 1/2016-1/2020, stratified by statewide COVID-19 incidence. Overall, from 3/15 to 4/30, new listings were 11% fewer than expected (IRR = _0.84 0.89_0.93 ), LDLTs were 49% fewer (IRR = _0.37 0.51_0.72 ), and DDLTs were 9% fewer (IRR = _0.85 0.91_0.97 ). In May, new listings were 21% fewer (IRR = _0.74 0.79_0.84 ), LDLTs were 42% fewer (IRR = _0.39 0.58_0.85 ) and DDLTs were 13% more (IRR = _1.07 1.15_1.23 ). Centers in states with the highest incidence 3/15-4/30 had 59% more waitlist deaths (IRR = _1.09 1.59_2.32 ) and 34% fewer DDLTs (IRR = _0.50 0.66_0.86 ). By August, waitlist outcomes were occurring at expected rates, except for DDLT (13% more across all incidences). While the early COVID-affected states endured major transplant practice changes, later in the pandemic the newly COVID-affected areas were not impacted to the same extent. These results speak to the adaptability of the transplant community in addressing the pandemic and applying new knowledge to patient care.

Importance:Historically, deceased organ donation was lower among Black compared with White populations, motivating efforts to reduce racial disparities. The overarching effect of these efforts in Black and other racial/ethnic groups remains unclear. Objective:To examine changes in deceased organ donation over time. Design, Setting, and Participants:This population-based cohort study used data from January 1, 1999, through December 31, 2017, from the Scientific Registry of Transplant Recipients to quantify the number of actual deceased organ donors, and from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Detailed Mortality File to quantify the number of potential donors (individuals who died under conditions consistent with organ donation). Data were analyzed from December 2, 2019, to May 14, 2020. Exposures:Race and ethnicity of deceased and potential donors. Main Outcomes and Measures:For each racial/ethnic group and year, a donation ratio was calculated as the number of actual deceased donors divided by the number of potential donors. Direct age and sex standardization was used to allow for group comparisons, and Poisson regression was used to quantify changes in donation ratio over time. Results:A total of 141 534 deceased donors and 5 268 200 potential donors were included in the analysis. Among Black individuals, the donation ratio increased 2.58-fold from 1999 to 2017 (yearly change in adjusted incidence rate ratio [aIRR], 1.05; 95% CI, 1.05-1.05; P < .001). This increase was significantly greater than the 1.60-fold increase seen in White individuals. Nevertheless, substantial racial differences remained, with Black individuals still donating at only 69% the rate of White individuals in 2017 (P < .001). Among other racial minority populations, changes were less drastic. Deceased organ donation increased 1.80-fold among American Indian/Alaska Native and 1.40-fold among Asian or Pacific Islander populations, with substantial racial differences remaining in 2017 (American Indian/Alaska Native population donation at 28% and Asian/Pacific Islander population donation at 85% the rate of the White population). Deceased organ donation differences between Hispanic/Latino and non-Hispanic/Latino populations increased over time (4% lower in 2017). Conclusions and Relevance:The findings of this cohort study suggest that differences in deceased organ donation between White and some racial minority populations have attenuated over time. The greatest gains were observed among Black individuals, who have been the primary targets of study and intervention. Despite improvements, substantial differences remain, suggesting that novel approaches are needed to understand and address relatively lower rates of deceased organ donation among all racial minorities.

BACKGROUND:clinical and imaging investigations allow a detailed assessment of an organ donor, but a quota of cancer still elude detection. Complete autopsy of donors is even less frequently performed, due to economic issues and increasing availability of high-quality imaging. The aim of this study is to gather evidence from the literature on donor malignancy discovered at autopsy following organ donation and to discuss the utility and limitations of autopsy practice in the field of transplantation. METHODS:A systematic search according to PRISMA guidelines was carried out in Pubmed and Embase databases until September 2020 to select articles with reporting of cancer discovered in a donor at postmortem examination. Cancer discover in not-transplant setting were excluded. A descriptive synthesis was provided. RESULTS:Of 7388 articles after duplicates removal, 56 were included. Fifty-one studies reported on complete autopsy, while 5 dealt only with limited autopsy (prostate and central nervous system). The number of autopsies ranged between 1 and 246 with a total of 823 autopsies performed. The most frequent cancer discovered at autopsy was lymphoma (n = 13, 15%), followed by renal cell carcinoma (RCC) (n = 11, 13%), non-small cell lung cancer (NSCLC) (n = 10, 11%), melanoma (n = 10, 11%), choriocarcinoma (n = 6, 7%) and glioblastoma (GBM) (n = 6, 7%). CONCLUSIONS:Lymphoma and melanoma are still difficult-to-detect cancers both during donor investigation and at procurement, whilst prostate cancer and choriocarcinoma are almost always easily detected nowadays thank to blood markers and clinical examination. There have been improvements with time in pre-donation detection procedures which are now working well, particularly when complete imaging investigations are performed, given that detection rate of CT/MRI is high and accurate. Autopsy can play a role to help to establish the correct donor management pathways in case of cancer discover. Furthermore, it helps to better understand which cancers are still eluding detection and consequently to refine guidelines' assessment procedures.

Background/UNASSIGNED:Despite the revolutionary role of direct-acting antivirals for hepatitis C virus (HCV), the treatment timing for liver transplant candidates remains controversial. We hypothesize that deferring treatment until after liver transplantation improves access to a larger and higher-quality donor pool without a detrimental impact on post-liver transplantation outcomes. Methods/UNASSIGNED:This single-center study includes recipients that underwent deceased-donor liver transplant with HCV as the primary indication January 1, 2014, to December 31, 2018. For recipients that were untreated (n = 87) versus treated (n = 42) pre-LT, we compared post-LT mortality using Cox regression with inverse probability of treatment-weighted data. Results/UNASSIGNED: = 0.06). Conclusions/UNASSIGNED:Deferring HCV treatment improves access to higher-quality donors and may improve post-LT survival.

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.77 1.40_2.56 ,P = .3) and moderately (wIRR = _0.88 1.35_2.06 ,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.33 2.22_3.72 ,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.62 3.57_4.88 , P < .001) and death-censored graft loss (wHR = _1.15 4.01_13.95 ,P = .03). Post-KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = _1.03 1.68_2.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = _1.45 2.09_3.02 ; PFNC = _1.67 2.40_3.46 ; PCC = _1.48 2.24_3.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = _1.34 1.62_1.95 ) than CLDKT (aHR = _1.96 2.29_2.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.