Faculty Bibliography

Kidney transplant recipients (KTRs) develop decreased antibody titers to SARS-CoV-2 vaccination compared to healthy controls (HCs), but whether KTRs generate antibodies against key epitopes associated with neutralization is unknown. Plasma from 78 KTRs from a clinical trial of third doses of SARS-CoV-2 vaccines and 12 HCs underwent phage display immunoprecipitation and sequencing (PhIP-Seq) to map antibody responses against SARS-CoV-2. KTRs had lower antibody reactivity to SARS-CoV-2 than HCs, but KTRs and HCs recognized similar epitopes associated with neutralization. Thus, epitope gaps in antibody breadth of KTRs are unlikely responsible for decreased efficacy of SARS-CoV-2 vaccines in this immunosuppressed population.

BACKGROUND:Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D+), it is crucial to understand whether this has impacted transplant rates for this population. METHODS:Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D+ kidneys (HOPE) compared with 46 025 candidates not listed for D+ kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D+, false-positive [FP; donor with false-positive HIV testing], D- [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS:HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D+, 34% D-, 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D-, 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates (P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS:Listing for D+ kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

BACKGROUND:Cytomegalovirus (CMV)-seronegative lung transplant recipients (LTRs) with seropositive donors (CMV D+/R-) have the highest mortality of all CMV serostatuses. Due to immunosenescence and other factors, we hypothesized CMV D+/R- status might disproportionately impact older LTRs. Thus, we investigated whether recipient age modified the relationship between donor CMV status and mortality among CMV-seronegative LTRs. METHODS:Adult, CMV-seronegative first-time lung-only recipients were identified through the Scientific Registry of Transplant Recipients between May 2005 and December 2019. We used adjusted multivariable Cox regression to assess the relationship of donor CMV status and death. Interaction between recipient age and donor CMV was assessed via likelihood ratio testing of nested Cox models and by the relative excess risk due to interaction (RERI) and attributable proportion (AP) of joint effects. RESULTS:We identified 11,136 CMV-seronegative LTRs. The median age was 59 years; 65.2% were male, with leading transplant indication of idiopathic pulmonary fibrosis (35.6%); and 60.8% were CMV D+/R-. In multivariable modeling, CMV D+/R- status was associated with 27% increased hazard of death (adjusted hazard ratio: 1.27, 95% confidence interval: 1.21-1.34) compared to CMV D-/R-. Recipient age ≥60 years significantly modified the relationship between donor CMV-seropositive status and mortality on the additive scale, including RERI 0.24 and AP 11.4% (p = 0.001), that is, the interaction increased hazard of death by 0.24 and explained 11.4% of mortality in older CMV D+ recipients. CONCLUSIONS:Among CMV-seronegative LTRs, donor CMV-seropositive status confers higher risk of posttransplant mortality, which is amplified in older recipients. Future studies should define optimal strategies for CMV prevention and management in older D+/R- LTRs.

Obesity is a chronic, relapsing disease that increases the risks of living kidney donation; at the same time, transplant centers have liberalized body mass index constraints for donors. With the increasing number of anti-obesity medications available, the treatment of obesity with anti-obesity medications may increase the pool of potential donors and enhance donor safety. Anti-obesity medications are intended for long-term use given the chronic nature of obesity. Cessation of treatment can be expected to lead to weight regain and increases the risk of comorbidity rebound/development. In addition, anti-obesity medications are meant to be used in conjunction with-rather than in replacement of-diet and physical activity optimization. Anti-obesity medication management includes selecting medications that may ameliorate any co-existing medical conditions, avoiding those that are contraindicated in such conditions, and being sensitive to any out-of-pocket expenses that may be incurred by the potential donor. A number of questions remain regarding who will and should shoulder the costs of long-term obesity treatment for donors. In addition, future studies are needed to quantify the degree of weight loss and duration of weight loss maintenance needed to normalize the risk of adverse kidney outcomes relative to comparable non-donors and lower weight donors.

BACKGROUND:Frailty is associated with poor outcomes in surgical patients including kidney transplant recipients. Transplant centers that measure frailty have better pre- and post-operative outcomes. However, clinical utility of existing tools is low due to time constraints. To address this major barrier to implementation in the pre-operative evaluation of patients, we developed an abridged frailty phenotype. METHODS:The abridged frailty phenotype was developed by simplifying the 5 Physical Frailty Phenotype (PFP) components in a two-center prospective cohort of 3,220 kidney transplant candidates and tested for efficiency (time to completion) in 20 candidates evaluation (1/2009-3/2020). We examined area under curve (AUC) and Cohen's kappa agreement to compare the abridged assessment with the PFP. We compared waitlist mortality risk (competing risks models) by frailty using the PFP and abridged assessment, respectively. Model discrimination was assessed using Harrell's C-statistic. RESULTS:Of 3,220 candidates, the PFP and abridged assessment identified 23.8% and 27.4% candidates as frail, respectively. The abridged frailty phenotype had substantial agreement (kappa=0.69, 95%CI:0.66-0.71) and excellent discrimination (area under the curve=0.861). Among 20 patients at evaluation, abridged assessment took 5-7 minutes to complete. The PFP and abridged assessment had similar associations with waitlist mortality (subdistribution hazard ratio [SHR]=1.62, 95%CI:1.26-2.08 vs. SHR=1.70, 95%CI:1.33-2.16) and comparable mortality discrimination (p=0.51). CONCLUSIONS:The abridged assessment is an efficient and valid way to identify frailty. It predicts waitlist mortality without sacrificing discrimination. Surgical departments should consider utilizing the abridged assessment to evaluate frailty in patients when time is limited.

BACKGROUND:Biliary complications (BCs) continue to impact patient and graft survival after liver transplant (LT), despite improvements in organ preservation, surgical technique, and posttransplant care. Real-world evidence provides a national estimate of the incidence of BC after LT, implications for patient and graft outcomes, and attributable cost not available in transplant registry data. METHODS:An administrative health claims-based BC identification algorithm was validated using electronic health records (N = 128) and then applied to nationally linked Medicare and transplant registry claims. RESULTS:The real-world evidence algorithm identified 97% of BCs in the electronic health record review. Nationally, the incidence of BCs within 1 y of LT appears to have improved from 22.2% in 2002 to 20.8% in 2018. Factors associated with BCs include donor type (living versus deceased), recipient age, diagnosis, prior transplant, donor age, and donor cause of death. BCs increased the risk-adjusted hazard ratio (aHR) for posttransplant death (aHR, 1.43; P  < 0.0001) and graft loss (aHR, 1.48; P  < 0.0001). Nationally, BCs requiring intervention increased risk-adjusted first-year Medicare spending by $39 710 ( P  < 0.0001). CONCLUSIONS:BCs remain an important cause of morbidity and expense after LT and would benefit from a systematic quality-improvement program.

BACKGROUND:Disparities in pediatric kidney transplantation (KT) result in reduced access and worse outcomes for minority children. We assessed the impact of recent systems changes on these disparities. METHODS:This is a retrospective cohort study of pediatric patients utilizing data from the US Renal Data System (n = 7547) and Scientific Registry of Transplant Recipients (n = 6567 waitlisted and n = 6848 transplanted patients). We compared access to transplantation, time to deceased donor kidney transplant (DDKT), and allograft failure (ACGF) in the 5 years preceding implementation of the Kidney Allocation System (KAS) to the 5 years post-KAS implementation 2010-2014 vs. 2015-2019, respectively. RESULTS:p = 0.05) while there was no difference in 3- or 5-year ACGF among LDKT recipients. CONCLUSIONS:After KAS implementation, there is equity in time to DDKT. Pre-KAS increased hazard of ACGF among Black children has decreased in the post-KAS era; however, persistent disparities exist in time to transplant listing among Black and Hispanic children when compared to white children. A higher resolution version of the Graphical abstract is available as Supplementary information.