Faculty Bibliography

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.

IMPORTANCE:Living donor kidney transplant (LDKT) is the ideal treatment for end-stage kidney disease, but racial disparities in LDKT have increased over the last 2 decades. Recipient clinical and social factors do not account for LDKT racial inequities, although comprehensive measures of community-level vulnerability have not been assessed. OBJECTIVE:To determine if racial disparities persist in LDKT independent of community-level vulnerability. DESIGN, SETTING, AND PARTICIPANTS:This retrospective, multicenter, cross-sectional study included data from 19 287 adult kidney-only transplant recipients in the Scientific Registry of Transplant Recipients. The study included individuals who underwent transplant between January 1 and December 31, 2018. EXPOSURES:Recipient race and the 2018 US Centers for Disease Control and Prevention Social Vulnerability Index (SVI). Census tract-level SVI data were linked to census tracts within each recipient zip code. The median SVI measure among the census tracts within a zip code was used to describe community-level vulnerability. MAIN OUTCOMES AND MEASURES:Kidney transplant donor type (deceased vs living). Modified Poisson regression was used to evaluate the association between SVI and LDKT, and to estimate LDKT likelihood among races, independent of community-level vulnerability and recipient-level characteristics. RESULTS:Among 19 287 kidney transplant recipients, 6080 (32%) received LDKT. A total of 11 582 (60%) were male, and the median (interquartile range) age was 54 (43-63) years. There were 760 Black LDKT recipients (13%), 4865 White LDKT recipients (80%), and 455 LDKT recipients of other races (7%; American Indian, Asian, multiracial, and Pacific Islander). Recipients who lived in communities with higher SVI (ie, more vulnerable) had lower likelihood of LDKT compared with recipients who lived in communities with lower SVI (ie, less vulnerable) (adjusted relative risk [aRR], 0.97; 95% CI, 0.96-0.98; P < .001). Independent of community-level vulnerability, compared with White recipients, Black recipients had 37% lower likelihood (aRR, 0.63; 95% CI, 0.59-0.67; P < .001) and recipients of other races had 24% lower likelihood (aRR, 0.76; 95% CI, 0.70-0.82; P < .001) of LDKT. The interaction between SVI and race was significant among Black recipients, such that the disparity in LDKT between Black and White recipients increased with greater community-level vulnerability (ratio of aRRs, 0.67; 95% CI, 0.51-0.87; P = .003). CONCLUSIONS AND RELEVANCE:Community-level vulnerability is associated with access to LDKT but only partially explains LDKT racial disparities. The adverse effects of living in more vulnerable communities were worse for Black recipients. The interaction of these constructs is worrisome and suggests evaluation of other health system factors that may contribute to LDKT racial disparities is needed.

BACKGROUND & AIMS:Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry. METHODS:A retrospective review of this prospective, multicenter cohort study of all APAP-ALF patients enrolled during the study period (1998-2018) was completed. Primary outcomes evaluated were the 21-day transplant-free survival (TFS) and neurologic complications. Covariates evaluated included enrollment cohort (early, 1998-2007; recent, 2008-2018), intentionality, psychiatric comorbidity, and use of organ support including continuous renal replacement therapy (CRRT). RESULTS:Of 1190 APAP-ALF patients, recent cohort patients (n = 608) had significantly improved TFS (recent, 69.8% vs early, 61.7%; P = .005). Recent cohort patients were more likely to receive CRRT (22.2% vs 7.6%; P < .001), and less likely to develop intracranial hypertension (29.9% vs 51.5%; P < .001) or die by day 21 from cerebral edema (4.5% vs 11.6%; P < .001). Grouped by TFS status (non-TFS, n = 365 vs TFS, n = 704), there were no differences in psychiatric comorbidity (51.5% vs 55.0%; P = .28) or intentionality (intentional, 39.7% vs 41.6%; P = .58). On multivariable logistic regression adjusting for vasopressor support, development of grade 3/4 hepatic encephalopathy, King's College criteria, and MELD score, the use of CRRT (odds ratio, 1.62; P = .023) was associated with significantly increased TFS (c-statistic, 0.86). In a second model adjusting for the same covariates, recent enrollment was associated significantly with TFS (odds ratio, 1.42; P = .034; c-statistic, 0.86). CONCLUSIONS:TFS in APAP-ALF has improved in recent years and rates of intracranial hypertension/cerebral edema have decreased, possibly related to increased CRRT use.

BACKGROUND:There are little data to compare the post-transplant survival between lung-liver transplant (LLT) and liver-alone recipients. This study was undertaken to compare survival between LLT and liver-alone transplant. METHODS:UNOS data for patients undergoing LLT from 2002 to 2017 was analyzed. LLT recipients (n = 81) were matched 1:4 to liver-alone recipients (n = 324) by propensity score and patient survival was compared in the matched cohorts. RESULTS:Unadjusted 1, 3, and 5-year patient survival in the matched cohort was significantly worse in the LLT (82.5%, 72.2%, and 62.2%) versus liver-alone (92.2%, 82.8%, and 80.9%; p = 0.005). This difference persisted after adjusting for covariates with residual imbalance (HR 2.05, 95% CI 1.37-3.08; p = 0.001). CONCLUSION/CONCLUSIONS:LLT has significantly worse survival than liver-alone transplant. With an increasing organ shortage, medical necessity criteria such as those developed for simultaneous liver-kidney transplantation should be developed for simultaneous lung-liver transplants to assure liver allografts are only allocated when truly needed.

OBJECTIVE:The aim of this study was to characterize end-stage renal disease (ESRD) patients with obesity as their only contraindication to listing and to quantify wait-list and transplant access. METHODS:Using the US Renal Data System, a retrospective cohort study of incident dialysis cases (2012 to 2014) was performed. The primary outcomes were time to wait-listing and time to transplantation. RESULTS:Of 157,572 dialysis patients not already listed, 39,844 had BMI as their only demonstrable transplant contraindication. They tended to be younger, female, and Black. Compared with patients with BMI < 35, those with BMI 35 to 39.9, 40 to 44.9, and ≥45 were, respectively, 15% (adjusted hazard ratio [aHR] 0.85; 95% CI: 0.83-0.88; p < 0.001), 45% (aHR 0.55; 95% CI: 0.52-0.57; p < 0.001), and 71% (aHR 0.29; 95% CI: 0.27-0.31; p < 0.001) less likely to be wait-listed. Wait-listed patients with BMI 35 to 39.9 were 24% less likely to achieve transplant (aHR 0.76; 95% CI: 0.72-0.80; p < 0.0001), BMI 40 to 44.9 were 21% less likely (aHR 0.79; 95% CI: 0.72-0.86; p < 0.0001), and BMI ≥ 45 were 15% less likely (aHR 0.85; 95% CI: 0.75-0.95; p = 0.004) compared with patients with BMI < 35. CONCLUSIONS:Obesity was the sole contraindication to wait-listing for 40,000 dialysis patients. They were less likely to be wait-listed. For those who were, they had a lower likelihood of transplant. Aggressive weight-loss interventions may help this population achieve wait-listing and transplant.

Several well-described manifestations of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. Among them, a transient elevation of liver enzymes is the typical presentation of coronavirus disease 2019 (COVID-19) liver-related injury. The mechanism of liver involvement is likely a combination of viral injury and immune-mediated inflammation. In contrast, acute liver failure in the setting of COVID-19 has rarely been reported. Herein, we report a case of pediatric acute liver failure in a previously healthy female adolescent infected with SARS-CoV-2 with biopsy evidence of replicating virus in hepatocytes, which has not been previously reported.