Faculty Bibliography

BACKGROUND:Frailty, a phenotype characterized by decreased physiologic reserve and the inability to recover following confrontation with a stressor like hemodialysis, may help identify which patients on incident hemodialysis will experience longer postdialysis recovery times. Recovery time is associated with downstream outcomes, including quality of life and mortality. We characterized postdialysis recovery times among patients new to hemodialysis and quantified the association between frailty and hemodialysis recovery time. METHODS:Among 285 patients on hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, frailty was measured using the Fried phenotype. Self-reported recovery time was obtained by telephone interview. We estimated the association of frailty (intermediately frail and frail versus nonfrail) and postdialysis recovery time using adjusted negative binomial regression. RESULTS:Median time between dialysis initiation and study enrollment was 3.4 months (IQR, 2.7-4.9), and that between initiation and recovery time assessment was 11 months (IQR, 9.3-15). Mean age was 55 years, 24% were >65 years, and 73% were Black; 72% of individuals recovered in ≤1 hour, 20% recovered in 1-6 hours, 5% required 6-12 hours to recover, and <5% required >12 hours to recover. Those with intermediate frailty, frailty, and age ≤65 years had 2.56-fold (95% CI, 1.45 to 4.52), 1.72-fold (95% CI, 1.03 to 2.89), and 2.35-fold (95% CI, 1.44 to 3.85) risks, respectively, of longer recovery time independent of demographic characteristics, comorbidity, and dialysis-related factors. CONCLUSIONS:In adults new to hemodialysis, frailty was independently associated with prolonged postdialysis recovery. Future studies should assess the effect of frailty-targeted interventions on recovery time to improve clinical outcomes.

BACKGROUND:Weight loss before kidney transplant (KT) is a known risk factor for weight gain and mortality, however, while unintentional weight loss is a marker of vulnerability, intentional weight loss might improve health. We tested whether pre-KT unintentional and intentional weight loss have differing associations with post-KT weight gain, graft loss and mortality. METHODS:Among 919 KT recipients from a prospective cohort study, we used adjusted mixed-effects models to estimate post-KT BMI trajectories, and Cox models to estimate death-uncensored graft loss, death-censored graft loss and all-cause mortality by 1-year pre-KT weight change category [stable weight (change ≤ 5%), intentional weight loss (loss > 5%), unintentional weight loss (loss > 5%) and weight gain (gain > 5%)]. RESULTS:The mean age was 53 years, 38% were Black and 40% were female. In the pre-KT year, 62% of recipients had stable weight, 15% had weight gain, 14% had unintentional weight loss and 10% had intentional weight loss. In the first 3 years post-KT, BMI increases were similar among those with pre-KT weight gain and intentional weight loss and lower compared with those with unintentional weight loss {difference +0.79 kg/m2/year [95% confidence interval (CI) 0.50-1.08], P < 0.001}. Only unintentional weight loss was independently associated with higher death-uncensored graft loss [adjusted hazard ratio (aHR) 1.80 (95% CI 1.23-2.62)], death-censored graft loss [aHR 1.91 (95% CI 1.12-3.26)] and mortality [aHR 1.72 (95% CI 1.06-2.79)] relative to stable pre-KT weight. CONCLUSIONS:This study suggests that unintentional, but not intentional, pre-KT weight loss is an independent risk factor for adverse post-KT outcomes.

BACKGROUND:Belatacept may impair humoral immunity, impacting the effectiveness of SARS-CoV-2 mRNA vaccines in transplant recipients. We investigated immunogenicity after SARS-CoV-2 mRNA vaccines in kidney transplant recipients who are and are not taking belatacept. METHODS:Participants were recruited between December 9, 2020, and April 1, 2021. Blood samples were collected after dose 1 and dose 2 (D1, D2) and analyzed using either an anti-SARS-CoV-2 enzyme immunoassay against the S1 domain of the SARS-CoV-2 spike protein or immunoassay against the receptor-binding domain of the SARS-CoV-2 spike protein. Stabilized inverse probability of treatment weights was used to compare immunogenicity, and a weighted logistics regression was used to calculate fold change of positive response. RESULTS:Among the 609 participants studied, 24 (4%) were taking belatacept. After dose 1, 0/24 (0%) belatacept patients had detectable antibodies, compared with 77 of 568 (14%) among the equivalent nonbelatacept population (P = 0.06). After dose 2, 1/19 (5%) belatacept patients had detectable antibodies, compared with 190/381 (50%) among the equivalent nonbelatacept population (P < 0.001). Belatacept use was associated with 16.7-fold lower odds of having a positive post-D2 titer result (P < 0.01). CONCLUSIONS:Additional measures need to be explored to protect kidney transplant recipients taking belatacept. Best safety practices should be continued despite vaccination among this population.

BACKGROUND:With stressors of dialysis prekidney transplantation (KT) and restoration of kidney function post-KT, it is likely that KT recipients experience a decline in functional status while on the waitlist and improvements post-KT. METHODS:We leveraged 224 832 KT recipients from the national registry (SRTR, February 1990-May 2019) with measured Karnofsky Performance Status (KPS, 0%-100%) at listing, KT admission, and post-KT. We quantified the change in KPS from listing to KT using generalized linear models. We described post-KT KPS trajectories using adjusted mixed-effects models and tested whether those trajectories differed by age, sex, race, and diabetes status using a Wald test among all KT recipients. We then quantified risk adverse post-KT outcomes (mortality and all-cause graft loss [ACGL]) by preoperative KPS and time-varying KPS. RESULTS:Mean KPS declined from listing (83.7%) to admission (78.9%) (mean = 4.76%, 95% confidence interval [CI]: -4.82, -4.70). After adjustment, mean KPS improved post-KT (slope = 0.89%/y, 95% CI: 0.87, 0.91); younger, female, non-Black, and diabetic recipients experienced greater post-KT improvements (Pinteractions < 0.001). Lower KPS (per 10% decrease) at admission was associated with greater mortality (adjusted hazard ratio [aHR] = 1.11, 95% CI: 1.10, 1.11) and ACGL (aHR = 1.08, 95% CI: 1.08, 1.09) risk. Lower post-KT KPS (per 10% decrease; time-varying) were more strongly associated with mortality (aHR = 1.93, 95% CI: 1.92, 1.94) and ACGL (aHR = 1.84, 95% CI: 1.83, 1.85). CONCLUSIONS:Functional status declines pre-KT and improves post-KT in the national registry. Despite post-KT improvements, poorer functional status at KT and post-KT are associated with greater mortality and ACGL risk. Because of its dynamic nature, clinicians should repeatedly screen for lower functional status pre-KT to refer vulnerable patients to prehabilitation in hopes of reducing risk of adverse post-KT outcomes.

In this study of 12 people with HIV (PWH) who received the first dose of SARS-CoV-2 mRNA vaccination, anti-SARS-CoV-2 receptor-binding domain antibodies were detectable in all participants; lower antibody levels were seen in those with lower CD4+ counts, and vaccine reactions were generally mild.

Background/UNASSIGNED:) transplantation involves ethical considerations related to safety, consent, stigma, and privacy, which could be better understood through studying patients' actual experiences. Methods/UNASSIGNED:transplantation at 4 centers regarding their decision-making process, the informed consent process, and posttransplant experiences. Participants were interviewed at-transplant (≤3 wk after transplant), posttransplant (≥3 mo after transplant), or both time points. Interviews were analyzed thematically using constant comparison of inductive and deductive coding. Results/UNASSIGNED:transplant candidates were unable to receive HIV-noninfected donor organs. Conclusions/UNASSIGNED:transplant candidates regarding available treatment options and for transplant teams regarding privacy and stigma concerns would be beneficial.

The SRTR maintains the liver-simulated allocation model (LSAM), a tool for estimating the impact of changes to liver allocation policy. Integral to LSAM is a model that predicts the decision to accept or decline a liver for transplant. LSAM implicitly assumes these decisions are made identically for adult and pediatric liver transplant (LT) candidates, which has not been previously validated. We applied LSAM's decision-making models to SRTR offer data from 2013 to 2016 to determine its efficacy for adult (≥18) and pediatric (<18) LT candidates, and pediatric subpopulations-teenagers (≥12 to <18), children (≥2 to <12), and infants (<2)-using the area under the receiver operating characteristic (ROC) curve (AUC). For nonstatus 1A candidates, all pediatric subgroups had higher rates of offer acceptance than adults. For non-1A candidates, LSAM's model performed substantially worse for pediatric candidates than adults (AUC 0.815 vs. 0.922); model performance decreased with age (AUC 0.898, 0.806, 0.783 for teenagers, children, and infants, respectively). For status 1A candidates, LSAM also performed worse for pediatric than adult candidates (AUC 0.711 vs. 0.779), especially for infants (AUC 0.618). To ensure pediatric candidates are not unpredictably or negatively impacted by allocation policy changes, we must explicitly account for pediatric-specific decision making in LSAM.