Background and objectivesFrailty, a syndrome distinct from comorbidity and disability, is clinically manifested as a decreased resistance to stressors and is present in up to 35% of patient with ESKD. It is associated with falls, hospitalizations, poor cognitive function, and mortality. Also, frailty is associated with poor outcomes after kidney transplant, including delirium and mortality. Frailty is likely also associated with decreased access to kidney transplantation, given its association with poor outcomes on dialysis and post-transplant. Yet, clinicians have difficulty identifying which patients are frail; therefore, we sought to quantify if frail kidney transplant candidates had similar access to kidney transplantation as nonfrail candidates.Design, setting, participants, & measurementsWe studied 7078 kidney transplant candidates (2009–2018) in a three-center prospective cohort study of frailty. Fried frailty (unintentional weight loss, grip strength, walking speed, exhaustion, and activity level) was measured at outpatient kidney transplant evaluation. We estimated time to listing and transplant rate by frailty status using Cox proportional hazards and Poisson regression, adjusting for demographic and health factors.ResultsThe mean age was 54 years (SD 13; range, 18–89), 40% were women, 34% were black, and 21% were frail. Frail participants were almost half as likely to be listed for kidney transplantation (hazard ratio, 0.62; 95% confidence interval, 0.56 to 0.69; P<0.001) compared with nonfrail participants, independent of age and other demographic factors. Furthermore, frail candidates were transplanted 32% less frequently than nonfrail candidates (incidence rate ratio, 0.68; 95% confidence interval, 0.58 to 0.81; P<0.001).ConclusionsFrailty is associated with lower chance of listing and lower rate of transplant, and is a potentially modifiable risk factor.

Frailty and markers of inflammation were associated with increased waitlist mortality risk, but only markers of inflammation significantly improved ESRD risk prediction. These findings help clarify the accelerated aging physiology of ESRD and highlight easy-to-measure markers of increased waitlist mortality risk.

†Co-first authors.Prediction models for post-kidney transplantation mortality have had limited success (C-statistics ≤0.70). Adding objective measures of potentially modifiable factors may improve prediction and, consequently, kidney transplant (KT) survival through intervention. The Short Physical Performance Battery (SPPB) is an easily administered objective test of lower extremity function consisting of three parts (balance, walking speed, chair stands), each with scores of 0-4, for a composite score of 0-12, with higher scores indicating better function. SPPB performance and frailty (Fried frailty phenotype) were assessed at admission for KT in a prospective cohort of 719 KT recipients at Johns Hopkins Hospital (8/2009 to 6/2016) and University of Michigan (2/2013 to 12/2016). The independent associations between SPPB impairment (SPPB composite score ≤10) and composite score with post-KT mortality were tested using adjusted competing risks models treating graft failure as a competing risk. The 5-year posttransplantation mortality for impaired recipients was 20.6% compared to 4.5% for unimpaired recipients (p < 0.001). Impaired recipients had a 2.30-fold (adjusted hazard ratio [aHR] 2.30, 95% confidence interval [CI] 1.12-4.74, p = 0.02) increased risk of postkidney transplantation mortality compared to unimpaired recipients. Each one-point decrease in SPPB score was independently associated with a 1.19-fold (95% CI 1.09-1.30, p < 0.001) higher risk of post-KT mortality. SPPB-derived lower extremity function is a potentially highly useful and modifiable objective measure for pre-KT risk prediction.

Despite decreased physiologic reserve, frail recipients experience improvement in post-KT physical and kidney disease-specific HRQOL better than nonfrail recipients.

Frail kidney transplant (KT) recipients may be particularly vulnerable to surgical stressors, resulting in delirium and subsequent adverse outcomes. We sought to identify the incidence, risk factors, and sequelae of post-KT delirium. We studied 125,304 adult KT recipients (1999-2014) to estimate delirium incidence in national registry claims. Additionally, we used a validated chart abstraction algorithm to identify post-KT delirium in 893 adult recipients (2009-2017) from a cohort study of frailty. Delirium sequelae were identified using adjusted logistic regression (length of stay ≥2 weeks and institutional discharge [skilled nursing or rehabilitation facility]) and adjusted Cox regression (death-censored graft loss and mortality). Only 0.8% of KT recipients had a delirium claim. In the cohort study, delirium incidence increased with age (18-49 years old: 2.0%; 50-64 years old: 4.6%; 65-75 years old: 9.2%; and ≥75 years old: 13.8%) and frailty (9.0% versus 3.9%); 20.0% of frail recipients aged ≥75 years old experienced delirium. Frailty was independently associated with delirium (odds ratio [OR], 2.05; 95% confidence interval [95% CI], 1.02 to 4.13; =0.04), but premorbid global cognitive function was not. Recipients with delirium had increased risks of ≥2-week length of stay (OR, 5.42; 95% CI, 2.76 to 10.66;<0.001), institutional discharge (OR, 22.41; 95% CI, 7.85 to 63.98; <0.001), graft loss (hazard ratio [HR], 2.73; 95% CI, 1.14 to 6.53; =0.03), and mortality (HR, 3.12; 95% CI, 1.76 to 5.54;<0.001). Post-KT delirium is a strong risk factor for subsequent adverse outcomes, yet it is a clinical entity that is often missed.

Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients. We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each. In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18-question Center for Epidemiologic Studies-Depression Scale (CES-D). Using adjusted Poisson regression and survival analysis, we tested whether depressive symptoms (CES-D score > 14) and frailty were associated with KT length of stay (LOS), death-censored graft failure (DCGF), and mortality. At KT admission, 10.0% of patients exhibited depressive symptoms, 16.3% were frail, and 3.6% had both. Recipients with depressive symptoms were more likely to be frail (aOR = 3.97, 95% CI: 2.28-6.91, P < 0.001). Recipients with both depressive symptoms and frailty had a 1.88 times (95% CI: 1.70-2.08, P < 0.001) longer LOS, 6.20-fold (95% CI:1.67-22.95, P < 0.01) increased risk of DCGF, and 2.62-fold (95% CI:1.03-6.70, P = 0.04) increased risk of mortality, compared to those who were nonfrail and without depressive symptoms. There was only evidence of synergistic effect of frailty and depressive symptoms on length of stay (P for interaction< 0.001). Interventions aimed at reducing pre-KT depressive symptoms and frailty should be explored for their impact on post-KT outcomes.

More than one-third of US adults have limited health literacy, putting them at risk of adverse clinical outcomes. We evaluated the prevalence of limited health literacy among 1578 adult kidney transplant (KT) candidates (May 2014-November 2017) and examined its association with listing for transplant and waitlist mortality in this pilot study. Limited health literacy was assessed at KT evaluation by using a standard cutoff score ≤5 on the Brief Health Literacy Screen (score range 0-12, lower scores indicate worse health literacy). We used logistic regression and adjusted Cox proportional hazards models to identify risk factors for limited health literacy and to quantify its association with listing and waitlist mortality. We found that 8.9% of candidates had limited health literacy; risk factors included less than college education (adjusted odds ratio [aOR] = 2.87, 95% confidence interval [CI]:1.86-4.43), frailty (aOR = 1.85, 95% CI:1.22-2.80), comorbidity (Charlson comorbidity index [1-point increase] aOR = 1.12, 95% CI: 1.04-1.20), and cognitive impairment (aOR = 3.45, 95% CI: 2.20-5.41) after adjusting for age, sex, race, and income. Candidates with limited health literacy had a 30% (adjusted hazard ratio = 0.70, 95% CI: 0.54-0.91) decreased likelihood of listing and a 2.42-fold (95% CI: 1.16- to 5.05-fold) increased risk of waitlist mortality. Limited health literacy may be a salient mechanism in access to KT; programs to aid candidates with limited health literacy may improve outcomes and reduce disparities.

IntroductionCognitive decline is common and increases mortality risk in hemodialysis patients. Intradialytic interventions like cognitive training (CT) and exercise training (ET) may preserve cognitive function.MethodsWe conducted a pilot randomized controlled trial of 20 hemodialysis patients to study the impact of 3 months of intradialytic CT (tablet-based brain games) (n = 7), ET (foot peddlers) (n = 6), or standard of care (SC) (n = 7) on cognitive function. Global cognitive function was measured by the Modified Mini Mental Status Exam (3MS), psychomotor speed was measured by Trail Making Tests A and B (TMTA and TMTB), and executive function was assessed by subtracting (TMTB − TMTA). Lower 3MS scores and slower TMTA and TMTB times reflected worse cognitive function. P values for differences were generated using analysis of variance, and 95% confidence intervals (CIs) and P values were generated from linear regression.ResultsPatients with SC experienced a decrease in psychomotor speed and executive function by 3 months (TMTA: 15 seconds; P = 0.055; TMTB: 47.4 seconds; P = 0.006; TMTB − TMTA; 31.7 seconds; P = 0.052); this decline was not seen among those with CT or ET (all P > 0.05). Compared with SC, the difference in the mean change in 3MS score was −3.29 points (95% CI: −11.70 to 5.12; P = 0.42) for CT and 4.48 points (95% CI: −4.27 to 13.22; P = 0.30) for ET. Compared with SC, the difference in mean change for TMTA was −15.13 seconds (95% CI: −37.64 to 7.39; P = 0.17) for CT and −17.48 seconds (95% CI: −41.18 to 6.22; P = 0.14) for ET, for TMTB, the difference was −46.72 seconds (95% CI: −91.12 to −2.31; P = 0.04) for CT and −56.21 seconds (95% CI: −105.86 to −6.56; P = 0.03) for ET, and for TMTB – TMTA, the difference was −30.88 seconds (95% CI: −76.05 to 14.28; P = 0.16) for CT and −34.93 seconds (95% CI: −85.43 to 15.56; P = 0.16) for ET.ConclusionPreliminary findings of our pilot study suggested that cognitive decline in psychomotor speed and executive function is possibly prevented by intradialytic CT and ET. These preliminary pilot findings should be replicated.