Faculty Bibliography

BACKGROUND:Extended-course enoxaparin is increasingly used after bariatric surgery to prevent venous thromboembolism (VTE), the leading cause of death after bariatric surgery. Direct oral anticoagulants are widely used for extended thromboprophylaxis outside of bariatric surgery and offered to patients in our program who cannot tolerate or obtain enoxaparin. We evaluated the safety and efficacy of apixaban 2.5 mg twice daily relative to a weight-based dose of enoxaparin 40 mg or 60 mg twice daily for 30 days after discharge following sleeve gastrectomy. METHODS:Patients aged ≥18 years who underwent laparoscopic sleeve gastrectomy from 2019 to 2024 at a single high-volume urban academic center were included. Bleeding and thrombosis outcomes within 30 days were compared between patients receiving enoxaparin 40 mg twice daily or apixaban 2.5 mg twice daily. Weighted modified Poisson analyses were used to obtain covariate balance and assess differences in bleeding and thrombosis events. RESULTS:A total of 5921 patients were included for analysis (5274 enoxaparin 40 mg twice daily, 486 enoxaparin 60 mg twice daily, and 161 apixaban 2.5 mg twice daily). The 30-day thrombosis rate was significantly lower with enoxaparin versus apixaban (.1% versus 1.9%, P < .001). The composite outcome (VTE, portomesenteric venous thrombosis, and major/minor bleeding) was also significantly lower with enoxaparin versus apixaban (1.7% versus 5.6%, P < .01). In adjusted analyses, apixaban was associated with a relative risk of 12.09 for thrombosis (95% confidence interval [CI], 5.71-31.18), 1.93 for bleeding (95% CI, 1.27-3.00), and 2.59 (95% CI, 2.06-3.27) for any adverse outcome relative to enoxaparin. CONCLUSION/CONCLUSIONS:Enoxaparin is associated with both lower thrombosis and bleeding rates compared with apixaban for extended thromboprophylaxis after sleeve gastrectomy.

BACKGROUND:Due to high prevalence of Kaposi Sarcoma (KS)-Associated Herpesvirus (KSHV) among people with HIV, KSHV-associated disease (KAD) may be increased after kidney transplantation from donors with HIV (HIV D+) to recipients with HIV (HIV R+). METHODS:Anti-KSHV antibodies were measured in HIV R+ and donors with and without HIV (HIV D-) using a 30-antigen multiplex assay within three multicenter kidney transplantation studies. KSHV seropositivity was defined as reactivity to conventional KSHV antigens (≥1 ORF73 or K8.1); reactivity to expanded 5-antigen and 30-antigen panels were also reported. Risk factors were identified using modified Poisson regression. Recipients were monitored for post-transplant anti-KSHV antibody changes and KAD. RESULTS:KSHV seroprevalence was 40.6% (143/352) among HIV R+, 25.2% (33/131) among HIV D+, and 7.5% (4/53) among HIV D-. In the multivariable model, only men who have sex with men (MSM) was associated with KSHV seropositivity: relative risk 1.51 (95% confidence interval [CI] 1.07-2.14) in recipients and 2.39 (95%CI 1.03-5.53) in donors. Among 418 HIV R+ (215 HIV D+/R+, 203 HIV D-/R+), there were 5 KAD cases (incidence 0.63 cases/100 person-years, 95%CI 0.26-1.52): 3 skin-only KS, 1 multicentric Castleman disease, 1 allograft KS. The allograft KS occurred in a female HIV D+/R+ and was likely donor-derived. Remaining KAD cases occurred in male HIV D-/R+ and were likely recipient KSHV reactivation or acquisition. CONCLUSIONS:In the United States, KSHV seroprevalence in donors and recipients with HIV was high, particularly among MSM. Reassuringly, KSHV-associated disease was rare, and primarily attributed to recipient rather than donor-derived KSHV.

BACKGROUND:Transplanting kidneys from donors with HIV to recipients with HIV has become standard clinical practice. However, donors with HIV may have higher prevalence of viral and bacterial infections and autoimmunity that could increase allograft rejection in recipients. METHODS:We included deceased kidney donors (60 with HIV and 41 without HIV) who participated in a multicenter prospective study of HIV kidney transplantation between April 2018-September 2021. Using Phage ImmunoPrecipitation Sequencing, we compared the human antibody repertoire (allergens, autoantibodies, viruses and bacterial toxins) between donors with and without HIV, and evaluated their association with recipient allograft rejection. Moderated t-tests were used to assess reactivity and a multivariate logistic regression model adjusted for donor sex and KDPI assessed the association between donor adenovirus reactivity and recipient allograft rejection. RESULTS:Compared to donors without HIV, donors with HIV had lower BMI and were more likely to be African American. The median number of positive autoantibodies was marginally higher among donors with HIV (499 [IQR = 357, 579]) compared to donors without HIV (395 [IQR = 256, 538] (P = 0.058). Donors with HIV additionally had significantly higher antibody reactivity to Epstein-Barr virus and cytomegalovirus (q < 0.05). Among all donors with and without HIV, antibodies to adenovirus were significantly associated with increased rejection among recipients, including after adjusting for false discovery (q < 0.05) and also adjusting for demographic factors using multivariable logistic regression (odds ratio = 4.97, 95% CI = 1.89-13.61). CONCLUSION/CONCLUSIONS:The presence of antibodies to adenovirus infection in kidney donors with HIV may be associated with allograft rejection. CLINICALTRIALS/RESULTS:gov NCT03500315. FUNDING/BACKGROUND:US National Institute of Health.

Pediatric deceased donor kidneys with acute kidney injury (ped-AKI) are at increased risk for non-utilization. To evaluate the post-transplant outcomes of ped-AKI recipients, we conducted a retrospective cohort study, comparing 17,731 adult recipients of kidneys from pediatric donors without AKI (ped-non-AKI, terminal serum creatinine (SCr)<1 mg/dL) to 1,589 ped-AKI recipients (SCr≥2 mg/dL). We used weighted logistic regression to estimate the association between ped-AKI and delayed graft function (DGF), and weighted Cox regression to estimate the association between ped-AKI and primary non-function (PNF) and all-cause graft failure (ACGF). Ped-AKI kidney recipients were at 6.0-fold (aOR=_5.325.98_6.72), 1.9-fold (aHR=_1.361.87_2.58), and 1.4-fold (aHR=_1.161.43_1.76) higher risk of DGF, PNF, and 1-year ACGF compared to ped-non-AKI recipients. En bloc ped-AKI recipients were at 5.6-fold (aOR=_3.295.57_9.43), 3.3-fold (aHR=_1.723.25_6.15), and 2.9-fold (aHR=_1.702.92_5.01) higher risk of DGF, PNF, 1-year ACGF compared to en bloc ped-non-AKI recipients. Among recipients of single kidneys from donors<20kg, ped-AKI recipients were at 8.9-fold (aOR=_4.348.87_18.12), 5-fold (aHR=_1.694.99_14.75), and 3.4-fold (aHR=_1.473.44_8.05) higher risk of DGF, PNF, 1-year ACGF compared to ped-non-AKI recipients. Ped-AKI kidney recipients have higher risks of early graft complications and failure. Risks are greatest for recipients of single kidneys from donors<20kg. Careful recipient selection and counseling are prudent when considering ped-AKI kidney offers.

BACKGROUND:Organ Procurement and Transplantation Network (OPTN) policy requires 2 years of follow-up for living kidney donors (LKDs); however, many transplant hospitals struggle to meet this requirement. We developed and tested a mobile health (mHealth) system for LKD follow-up in a pilot randomized-controlled trial (RCT). METHODS:LKDs were randomly assigned to either the intervention (mHealth + standard of care) or control arm (standard of care). We assessed OPTN policy-defined completeness and timeliness of 6-month, 1-year, and 2-year follow-ups. Four hundred LKDs were enrolled in the study (June 2018 to February 2021). RESULTS:At 6-month follow-up, a higher proportion of the intervention arm participants completed composite visits (97.5% vs. 91.5%, p = 0.01). Both arms had similar compliance rates at 1- and 2-year follow-up (92.0% vs. 89.5%, p = 0.49, and 66.5% vs. 65.0%, p = 0.83). Intervention arm participants completed 6-month follow-up 11 days earlier than their counterparts (p = 0.009). CONCLUSION/CONCLUSIONS:mHealth technologies improved 6-month follow-up, but did not impact 1- and 2-year LKD follow-up in this single-center RCT. Other strategies, such as providing services beyond data collection, may be necessary to improve donor engagement and support LDK's long-term follow-up.

BACKGROUND:Before KAS250 (circles-based allocation), donor service area (DSA) of listing was the largest contributor to deceased donor kidney transplantation (DDKT) rate disparities. Both before and after KAS250, it is unclear to what extent DSA-level disparities are attributable to center-level practice variation. We aimed to disentangle contributions to DDKT rate variation from: (1) center practices, (2) kidney distribution within sharp policy boundaries (DSAs, OPTN Regions), and (3) other geographic variation in kidney scarcity. METHODS:With national transplant registry data, we studied transplant rate variation in the pre-KAS250 era, which prioritized patients based on DSAs and Regions, and under KAS250, which prioritizes patients within 250 nautical mile circles. We modeled candidate DDKT rates with multilevel Poisson regression, adjusting for candidate factors, and calculated median incidence rate ratios (MIRR) to summarize variation attributable to DSAs, OPTN regions, states, census divisions, and to centers within those units. RESULTS:). Adjusted center-level DDKT rates under KAS250 were highly associated with offer acceptance rates (ρ = 0.60, p < 0.001). CONCLUSIONS:Though geographic disparities are driven primarily by center-level practice differences including offer acceptance, KAS250 did reduce DSA-level disparities. Further allocation policy changes are unlikely to substantially reduce geographic variation in DDKT rates.

INTRODUCTION/BACKGROUND:Predicting graft failure risk in pediatric liver transplantation (LT) recipients could identify areas for improving management. Persistent cognitive, motor, academic, and functional deficits are common in recipients and their impact on graft survival following LT helps inform risk prediction. METHODS:Using SRTR data 2008-2023, we evaluated the cognitive, motor, academic, and functional deficits of LT recipients at time of transplant to 14 years post-LT. We compared all cause graft failure (ACGF) among patients with versus without pre-LT and 1-year post-LT deficits using Cox regression, adjusting for recipient characteristics. We calculated an individual risk score for ACGF. RESULTS:In 8062 pediatric LT recipients median age 3 (IQR: 1, 10), 28.0%, 29.5%, 35.0%, and 79.8% of recipients had pre-LT deficits in cognition, motor, academic activity, and functional status respectively. This decreased to 23.0%, 18.1%, 14.2%, and 38.7% 1-year post-LT. Increased hazard of ACGF was noted in recipients with pre-LT decreased functional status (aHR = 1.13 (per 10% decrease), 95% CI: 1.10-1.15, p < 0.001), definite motor delay (aHR = 1.60, 95% CI: 1.21-2.10, p < 0.001), and inability to participate in academics (aHR = 1.49, 95% CI: 1.08-1.89, p = 0.01), but not delays in cognition (aHR = 0.91, 95% CI: 0.69-1.21, p = 0.19). Our risk score predicting ACGF demonstrated improved predictive performance compared to clinical parameters alone (C-statistic = 0.70 (0.67, 0.72) vs. 0.66 (0.64, 0.69), p < 0.001). CONCLUSIONS:Pediatric LT recipients with pre- or post-LT motor, academic, and functional deficits are at higher risk for ACGF. Care should be taken to assess deficits to identify patients who may benefit from functional intervention to potentially reduce ACGF risk.

BACKGROUND:Kidney transplantation (KT) from donors with human immunodeficiency virus (HIV-1) to recipients with HIV (HIV D+/R+) is noninferior to KT from donors without HIV (HIV D-/R+) with regard to safety. However, there may be differences in posttransplant infections. METHODS:We performed a secondary analysis of the HOPE in Action KT Study (NCT02602262) comparing the time to first clinically relevant infection within 24 months posttransplantation in 99 HIV D+/R+ versus 99 HIV D-/R+. Secondary outcomes included incidence rates, infection-related death, and timing of clinically relevant infection, each stratified by donor HIV status. RESULTS:The cumulative incidence of a clinically relevant infection at 24 months posttransplantation was 73.8% (95% confidence interval [CI]: 63.1%-81.2%) for HIV D+/R+ versus 64.7% (95% CI: 53.0%-73.4%) for HIV D-/R+. Comparing time to first clinically relevant infection in HIV D+/R+ versus HIV D-/R+, the adjusted hazard ratio (aHR) was 1.44 (95% CI: 1.01-2.04) at 24 months posttransplantation; for infections associated with hospitalization, the aHR was not significantly higher (1.21 [95% CI: .78-1.86). There were no significant differences in the number of infections, death from infection, duration, or site of infection between HIV D+/R+ versus HIV D-/R+, though viral infections were numerically more common in HIV D+/R+ (40% vs 35%). CONCLUSIONS:Although there was a statistically significant association between receipt of a kidney from a donor with HIV and time to first clinically relevant infection in the 24 months posttransplantation, there were no differences in infections associated with hospitalization. These data are overall reassuring as this emerging practice expands into clinical care. Clinical Trials Registration. NCT02602262.