Faculty Bibliography

Impaired cognition in liver recipients has been studied in the immediate posttransplant period but is poorly understood in the long term, despite its importance to quality of life. In a single-center cohort of liver recipients transplanted in 2010-2022 and >1 year after transplant, we assessed cognitive performance using a telephone-based battery. We compared depression, anxiety, and self-reported function by cognitive performance using descriptive statistics. Among 120 participants (median age 65, median 7.3 y after transplant), 25% had below-expectation cognition, 53% at-expectation cognition, and 22% above-expectation. Baseline characteristics were similar between groups. Below-expectation performance was most commonly observed in verbal learning (28%) and verbal memory (22%). Overall, 46% had symptoms of depression (38%) and/or anxiety (28%); anxiety was less common among those with above-expectation cognition (0%) versus below-expectation (34%) or at-expectation cognition (38%, p=0.01). The impaired global daily function was reported by 36% of recipients but was not associated with objective cognitive performance. Below-expectation cognition was prevalent among 25% of liver recipients at least 1 year after transplant and was associated with a higher likelihood of reporting psychiatric distress. These findings underscore the need for longitudinal assessment of cognitive and mental health outcomes among recipients of liver transplants.

INTRODUCTION/BACKGROUND:Early post-kidney transplant (KT) changes likely impact body composition, resulting in adverse post-KT outcomes. We estimated post-KT trajectories of computed tomography (CT)-based muscle quantity/quality and tested whether they were associated with mortality and death-censored graft loss (DCGL) among frail and nonfrail recipients. METHODS:We leveraged a cohort of 294 adult KT recipients (December 2008-February 2020) with CT measurements (muscle quantity: skeletal muscle index; muscle quality: skeletal muscle radiation attenuation). We used mixed linear regression models to estimate 3-year post-KT muscle quantity/quality trajectories. Cox proportional hazard models quantified the association between time-varying pre-/post-KT muscle mass measurements and post-KT mortality and DCGL. RESULTS:) was associated with elevated mortality risk (aHR: 2.00, 95% CI: 1.08-3.70), but not among nonfrail recipients. Among older (≥65 years) recipients, lower muscle quantity was associated with increased DCGL risk (aHR: 2.70, 95% CI: 1.04-7.04), but not among younger recipients. Lower muscle quality (per 10 HU) was associated with elevated mortality (aHR: 2.23, 95% CI: 1.61-3.08) and DCGL (aHR: 1.90, 95% CI: 1.16-3.12) risk. CONCLUSION/CONCLUSIONS:Lower pre-/post-KT muscle quantity/quality were associated with higher risks of post-KT adverse outcomes. Pre-/post-KT rehabilitation to improve muscle quantity/quality may be an effective clinical intervention to minimize risks of adverse post-KT outcomes.

Kidney transplantation from donors with HIV has recently become standard clinical practice, but the plasma inflammatory profile is not well characterized. Thirty-two cytokines and chemokines were evaluated among donors with HIV (n = 63) and without HIV (n = 41). Wilcoxon rank sum test was used to compare cytokines between groups. Donors with and without HIV were generally similar in terms of characteristics, except those with HIV had a non-significantly lower kidney donor profile index, reflecting better graft survival, creatinine, and body mass index. Most cytokine and chemokine levels were similar between groups. However, median IL-8 levels were higher (p < 0.0015) in donors without HIV (32.6 pg/mL, IQR = 13.8-394.9) compared to donors with HIV (15.1 pg/mL, IQR = 8.4-35.5). There were no significant correlations between cytokine and chemokine concentrations and CD4 counts or HIV viral load. In summary, inflammatory profiles were similar or lower among donors with HIV compared to donors without HIV supporting the safety of this emerging kidney transplantation practice.

OBJECTIVE:Peripheral artery disease (PAD) is a common comorbidity among patients waitlisted for deceased donor kidney transplant (DDKT). However, some centers consider PAD a contraindication for transplant given the higher risk of post-operative complications. We aimed to examine the survival benefit of DDKT among patients with and without PAD. METHODS:We used data from the Scientific Registry of Transplant Recipients (SRTR) from January 2003 to December 2022 to identify all DDK waitlist candidates. Kaplan-Meier survival estimates and multivariable Cox proportional hazards models were used to compare patient mortality for those who received a DDKT versus those remaining on the waitlist, stratified by PAD status. RESULTS:506,785 candidates were listed for adult kidney-only transplant during the study period, of which 8.7% had PAD and 36.0% received a DDKT. After a median follow-up time of 3.21 years from waitlist activation [interquartile range 1.11-7.03 years], mortality varied significantly according to DDKT and PAD status. After adjusting for baseline differences, DDKT was associated with a significantly lower hazard of death compared to remaining on the waitlist, regardless of PAD status [adjusted hazards ratio (aHR) 0.45-0.60, P<0.001]. Further stratifying by sex, race and ethnicity, and diabetes status did not substantially alter these results. CONCLUSION/CONCLUSIONS:PAD includes a spectrum of diseases with varying mortality risks. As captured and dichotomized in the SRTR database, DDKT conferred a similar long-term benefit relative to remaining on the waitlist for candidates with and without PAD. Therefore, PAD should not be an absolute contraindication to DDKT.

[This corrects the article DOI: 10.1016/j.lana.2024.100895.].

Transplantation from donors with hepatitis C virus (HCV) viremia to recipients without HCV-viremia (HCV D⁺/R^-) is common, but no data exist for recipients with HIV or donors with HCV/HIV coinfection. We assessed outcomes of HCV D⁺/R^- transplants within 3 HIV Organ Policy Equity Act studies of HIV⁺ abdominal transplantation to recipients with HIV between 2017 and 2023. Eighteen kidney and 6 liver transplant recipients with HIV received organs from 19 donors with HCV viremia, including 7 with HCV/HIV coinfection. Median recipient age was 58 years, 96% were male, and median waitlist time was 1 year. All recipients had undetectable HIV RNA at time of transplant with median cluster of differentiation 4 count 499 cells/mm³. HCV/HIV-coinfected donors had median cluster of differentiation 4 count 210 cells/mm³, and 4 of the 7 had detectable HIV RNA. HCV treatment with direct-acting antivirals was initiated at median 33 days after transplant and sustained virologic response was achieved in 23 of the 23 treated recipients without HCV-related adverse events; data unavailable for 1 participant. Kaplan-Meier survival analysis demonstrated 100% 1-year and 96% 3-year survival. Graft survival was 96% at 1 and 3 years. HCV D⁺/R^- abdominal transplantation, including donors with HCV/HIV coinfection, demonstrates favorable patient and graft survival in recipients with HIV and is a viable strategy to increase organ utilization.

BACKGROUND:Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS:In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS:A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS:Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.

Human leukocyte antigen-level matching in US kidney allocation has been deemphasized due to its role in elevating racial disparities. Molecular matching based on eplets might improve risk stratification compared to antigen matching, but the magnitude of racial disparities in molecular matching is not known. To assign eplets unambiguously, we utilized a cohort of 5193 individuals with high-resolution allele-level human leukocyte antigen genotypes from the National Kidney Registry. Using repeated random sampling to simulate donor-recipient genotype pairings based on the ethnic composition of the historical US deceased-donor pool, we profiled the percentage of well-matched donors available for candidates by ethnicity. The prevalence of well-matched donors with 0-DR/DQ eplet mismatch was 3-fold less racially disparate for Black and Asian candidates and 2-fold less for Latino candidates compared to 0-ABDR antigen mismatches. Compared to 0-DR antigen mismatch, 0-DR eplet mismatch was 1.33-fold more racially disparate for Asian and 1.28-fold more for Latino, with similar disparity for Black candidates, whereas 0-DQ eplet mismatch reduced disparities, showing 1.26-fold less disparity for Black, 1.14-fold less for Latino, but 1.26-fold higher for Asian candidates. The prevalence of well-matched donors for candidates of different ethnicities varied according to which molecules were chosen to define a low-risk match.

Unauthorized immigrants and permanent residents may experience challenges in accessing kidney transplantation due to limited healthcare access, socioeconomic and cultural barriers. Understanding the United States (US) national landscape of kidney transplantation for non-citizens may inform policy changes. To evaluate this, we utilized two cohorts from the US national registry (2013-2023): 287,481 adult candidates for first transplant listing and 190,176 adult first transplant recipients. Citizenship was categorized as US citizen (reference), permanent resident, and presumed unauthorized immigrant. Negative binomial regression was used to quantify the incidence rate ratio over time by citizenship status. Cause-specific hazards models, with clustering at the state of listing/transplant, were used to calculate the adjusted hazard ratio of waitlist mortality, kidney transplant, and post-transplant outcomes (mortality/death-censored graft failure) by citizenship category. The crude proportion of presumed unauthorized immigrants listed increased over time (2013: 0.9%, 2023:1.9%). However, after accounting for case mix and waitlist size, there was no change in listing over time. Presumed unauthorized immigrants were less likely to experience waitlist mortality (adjusted Hazard Ratio 0.54, 95% Confidence Interval: 0.46-0.62), were more likely to obtain deceased donor kidney transplant (1.11: 1.05-1.18), but less likely to receive live donor (0.80: 0.71-0.90) or preemptive kidney transplant (0.52: 0.43- 0.62). When stratified by insurance status, presumed unauthorized immigrants on Medicaid were less likely to receive deceased donor kidney transplants compared to their citizen counterparts; however, presumed unauthorized immigrants with Private insurance or Medicare were more likely to receive deceased donor kidney transplants. Presumed unauthorized immigrants were less likely to experience post-transplant death (0.56: 0.43-0.69) and graft failure (0.69: 0.57-0.84). Residents had similar pre- and post-transplant outcomes. Despite the barriers to kidney transplantation faced by presumed unauthorized immigrants and residents in the US, better post-transplant outcomes for presumed unauthorized immigrants compared to citizens persisted, even after accounting for differences in patient characteristics.