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Background Frailty is associated with poor outcomes in surgical patients including kidney transplant (KT) recipients. Transplant centers that measure frailty have better pre- and postoperative outcomes. However, clinical utility of existing tools is low due to time constraints. To address this major barrier to implementation in the preoperative 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 KT candidates and tested for efficiency (time to completion) in 20 candidates evaluation (January 2009 to March 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 (AUC = 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  = .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. [ABSTRACT FROM AUTHOR]

Background Short and long sleep durations are associated with cognitive dysfunction. Given the increased prevalence of sleep abnormalities in the chronic kidney disease (CKD) population, we tested whether the association between sleep duration and cognitive function differed between older adults with and without CKD. Methods This was a study of 3215 older adults (age ≥60 years) enrolled in the National Health and Nutrition Examination Survey (2011–14) evaluating sleep duration, cognitive function (immediate recall, delayed recall, verbal fluency, executive function and processing speed and global cognition) and kidney function. We quantified the association between sleep duration and cognitive function using linear regression and tested whether the associations differed among those with CKD and without using a Wald test for interaction. Results Among 3215 participants, 13.3% reported 2–5 hours of sleep/day, 75.2% reported 6–8 hours, and 11.5% reported ≥9 hours. Persons with CKD were more likely to sleep ≥9 hours [odds ratio 1.73 (95% confidence interval 1.22–2.46)]. Among participants with CKD, those with a sleep duration ≥9 hours demonstrated worse global cognitive function (P for interaction = .01), immediate recall (P for interaction = .01) and verbal fluency (P for interaction = .004) than those with a sleep duration of 6–8 h; no differences were observed for participants with CKD who slept 2–5 hours. Among participants without CKD, sleep was not associated with any measures of cognitive function. Conclusions Longer sleep duration is associated with worse cognitive function only among persons with CKD, and global cognition, delayed recall and verbal fluency are particularly affected. Studies should identify interventions to improve sleep patterns and quality in this population. [ABSTRACT FROM AUTHOR]

Background Frailty is common and associated with poor outcomes among kidney transplant (KT) recipients. While frailty improves in the first 3 months post-KT with restored kidney function, longer-term trajectories are likely to plateau/decline due to aging and other stressors (eg, immunosuppression). We evaluated longer-term post-KT trajectories of the physical frailty phenotype (PFP) and its components in adult patients at 2 centers. Methods PFP components were measured at admission, 1, 3, 6 months, 1 year, and annually thereafter post-KT. We used adjusted mixed-effects models to describe repeated measures of continuous components (weight, gait speed, grip strength, activity) and generalized estimating equations to quantify longitudinal, binomial response patterns (PFP; exhaustion). Results Among 1 336 recipients (mean age = 53) followed for a median of 1.9 years (interquartile range [IQR] = 0.1–3.2), likelihood of frailty declined in the first 2.5 years post-KT (adjusted odds ratio [aOR] = 0.96, 95% confidence interval [CI]: 0.95, 0.98), but increased after 2.5 years post-KT (aOR = 1.03, 95% CI: 1.00, 1.05). In the first 2.5 years post-KT, recipients demonstrated increases in weight (0.4 lbs/month, 95% CI: 0.3, 0.5), grip strength (0.2 kg/month, 95% CI: 0.1, 0.2), and activity (23.9 kcal/month, 95% CI: 17.5, 30.2); gait speed remained stable (−0.01 s/month, 95% CI: 0.01, 0.003). Additionally, likelihood of becoming exhausted declined post-KT (OR = 0.99, 95% CI: 0.98, 1.00). After 2.5 years post-KT, recipients demonstrated decreased grip strength (−0.07 kg/month, 95% CI: −0.12, −0.01) and activity (−20 kcal/month, 95% CI: −32.3, −8.2); they had stable weight (−0.003 lbs/month, 95% CI: −0.17, 0.16), gait speed (−0.003 s/month, 95% CI: −0.02, 0.01), and likelihood of becoming exhausted (OR = 1.01, 95% CI: 0.99, 1.02). Conclusion Despite frailty improvements in the first 2.5 years, recipients' frailty worsened after 2.5 years post-KT. Specifically, they experienced gains in strength, activity, and exhaustion in the first 2.5 years post-KT, but declined in strength and activity after 2.5 years post-KT while experiencing persistent slowness. Clinicians should consider monitoring recipients for worsening frailty after 2.5 years despite shorter-term improvements. [ABSTRACT FROM AUTHOR]

Background Cognitive impairment is common among persons with chronic kidney disease (CKD), due in part to reduced kidney function. Given that physical activity (PA) is known to mitigate cognitive decline, we examined whether associations between CKD stage and global/domain-specific cognitive function differ by PA. Methods We leveraged 3223 participants (≥60 years of age) enrolled in National Health and Nutrition Examination Survey (NHANES, 2011–2014), with at least one measure of objective cognitive function [immediate recall (CERAD-WL), delayed recall (CERAD-DR), verbal fluency (AF), executive function/processing speed (DSST), global (average of four tests) or self-perceived memory decline (SCD)]. We quantified the association between CKD stage {no CKD: estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 and albuminuria [albumin:creatinine ratio (ACR)] <30 mg/g; stages G1–G3: eGFR ≥60 mL/min/1.73 m2 and ACR ≥30 mg/g or eGFR 30–59 mL/min/1.73 m2; stages G4 and G5: eGFR <30 mL/min/1.73 m2} and cognitive function using linear regression (objective measures) and logistic regression (SCD), accounting for sampling weights for nationally representative estimates. We tested whether associations differed by PA [Global Physical Activity Questionnaire, high PA ≥600 metabolic equivalent of task (MET) · min/week versus low PA <600 MET · min/week] using a Wald test. Results Among NHANES participants, 34.9% had CKD stages G1–G3, 2.6% had stages G4 and G5 and 50.7% had low PA. CKD stages G4 and G5 were associated with lower global cognitive function {difference = −0.38 standard deviation [SD] [95% confidence interval (CI) −0.62 to −0.15]}. This association differed by PA (Pinteraction = 0.01). Specifically, among participants with low PA, those with CKD stages G4 and G5 had lower global cognitive function [difference = −0.57 SD (95% CI −0.82 to −0.31)] compared with those without CKD. Among those with high PA, no difference was found [difference = 0.10 SD (95% CI −0.29–0.49)]. Similarly, the CKD stage was only associated with immediate recall, verbal fluency, executive function and processing speed among those with low PA; no associations were observed for delayed recall or self-perceived memory decline. Conclusions CKD is associated with lower objective cognitive function among those with low but not high PA. Clinicians should consider screening older patients with CKD who have low PA for cognitive impairment and encourage them to meet PA guidelines. [ABSTRACT FROM AUTHOR]

Background Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT. Methods Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure. Results Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56–0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (P interaction = .02) and race (P interaction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54–0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46–0.57) or Black race (aHR = 0.51, 95% CI: 0.48–0.53) having a greatest reduction in dementia risk. Conclusion Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients. [ABSTRACT FROM AUTHOR]

Introduction: A comprehensive geriatric assessment (CGA) tailored to the chronic kidney disease (CKD) population would yield a more targeted approach to assessment and care. We aimed to identify domains of a CKD-specific CGA (CKD-CGA), characterize patterns of these domains, and evaluate their predictive utility on adverse health outcomes. Methods: We used data from 864 participants in the Chronic Renal Insufficiency Cohort aged ≥55 years and not on dialysis. Constituents of the CKD-CGA were selected a priori. Latent class analysis informed the selection of domains and identified classes of participants based on their domain patterns. The predictive utility of class membership on mortality, dialysis initiation, and hospitalization was examined. Model discrimination was assessed with C-statistics. Results: The CKD-CGA included 16 domains: cardiovascular disease, diabetes, five frailty phenotype components, depressive symptoms, cognition, five kidney disease quality-of-life components, health literacy, and medication use. A two-class latent class model fit the data best, with 34.7% and 65.3% in the high- and low-burden of geriatric conditions classes, respectively. Relative to the low-burden class, participants in the high-burden class were at increased risk of mortality (aHR = 2.09; 95% CI: 1.56, 2.78), dialysis initiation (aHR = 1.63; 95% CI: 1.06, 2.52), and hospitalization (aOR = 2.00; 95% CI: 1.38, 2.88). Model discrimination was the strongest for dialysis initiation (C-statistics = 0.86) and moderate for mortality and hospitalization (C-statistics = 0.70 and 0.66, respectively). Conclusion: With further validation in an external cohort, the CKD-CGA has the potential to be used in nephrology practices for assessing and managing geriatric conditions in older adults with CKD. [ABSTRACT FROM AUTHOR]

The allocation of scarce deceased donor kidneys is a complex process. Transplant providers are increasingly relying on constructs such as frailty and cognitive function to guide kidney transplant (KT) candidate selection. Patient views of the ethical issues surrounding the use of such constructs are unclear. We sought to assess KT candidates' attitudes and beliefs about the use of frailty and cognitive function to guide waitlist selection. KT candidates were randomly recruited from an ongoing single-center cohort study of frailty and cognitive function. Semi-structured interviews were conducted, and thematic analysis was performed. Inductively derived themes were mapped onto bioethics principles. Twenty interviews were conducted (65% contact rate, 100% participation rate) (60% male; 70% White). With respect to the use of frailty and cognitive function in waitlisting decisions, four themes emerged in which participants: (1) valued maximizing a scarce resource (utility); (2) prioritized equal access to all patients (equity); (3) appreciated a proportional approach to the use of equity and utility (precautionary utility); and (4) sought to weigh utility- and equity-based concerns regarding social support. While some participants believed frailty and cognitive function were useful constructs to maximize utility, others believed their use would jeopardize equity. Patients were uncomfortable with using single factors such as frailty or cognitive impairment to deny someone access to transplantation; participants instead encouraged using the constructs to identify opportunities for intervention to improve frailty and cognitive function prior to KT. KT candidates' values mirrored the current allocation strategy, seeking to balance equity and utility in a just manner, albeit with conflicting viewpoints on the appropriate use of frailty and cognitive impairment in waitlisting decisions. [ABSTRACT FROM AUTHOR]

Background: Younger kidney transplant (KT) candidates and recipients may have cognitive impairment due to chronic diseases and reliance on dialysis. Methods: To quantify cognitive impairment burden by age across the KT care continuum, we leveraged a two‐center cohort study of 3854 KT candidates at evaluation, 1114 recipients at admission, and 405 recipients at 1‐year post‐KT with measured global cognitive performance (3MS) or executive function (Trail Making Test). We also estimated burden of severe cognitive impairment that affects functional dependence (activities of daily living [ADL] < 6 or instrumental activities of daily living [IADL] < 8). Results: Among KT candidates, global cognitive impairment (18–34 years: 11.1%; 35–49 years: 14.0%; 50–64 years: 19.5%; ≥65 years: 22.0%) and severe cognitive impairment burden (18–34 years: 1.1%; 35–49 years: 3.0%; 50–64 years: 6.2%; ≥65 years: 7.7%) increased linearly with age. Among KT recipients at admission, global cognitive impairment (18–34 years: 9.1%; 35–49 years: 6.1%; 50–64 years: 9.3%; ≥65 years: 15.7%) and severe cognitive impairment burden (18–34 years: 1.4%; 35–49 years: 1.4%; 50–64 years: 2.2%; ≥65 years: 4.6%) was lower. Despite lowest burden of cognitive impairment among KT recipients at 1‐year post‐KT across all ages (18–34 years: 1.7%; 35–49 years: 3.4%; 50–64 years: 4.3%; ≥65 years: 6.5%), many still exhibited severe cognitive impairment (18–34 years:.0%; 35–49 years: 1.9%; 50–64 years: 2.4%; ≥65 years: 3.5%). Conclusion: Findings were consistent for executive function impairment. While cognitive impairment increases with age, younger KT candidates have a high burden comparable to community‐dwelling older adults, with some potentially suffering from severe forms. Transplant centers should consider routinely screening patients during clinical care encounters regardless of age. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives frail older adults may be more vulnerable to stressors, resulting in steeper declines in cognitive function. Whether the frailty–cognition link differs by cognitive domain remains unclear; however, it could lend insight into underlying mechanisms. Methods we tested whether domain-specific cognitive trajectories (clock-drawing test, (CDT), immediate and delayed recall, orientation to date, time, president and vice-president naming) measured annually (2011–2016) differ by baseline frailty (physical frailty phenotype) in the National Health and Aging Trends Study (n  = 7,439), a nationally representative sample of older adult U.S. Medicare beneficiaries, using mixed effects models to describe repeated measures of each cognitive outcome. To determine if the association between frailty and subsequent cognitive change differed by education, we tested for interaction using the Wald test. Results we observed steeper declines for frail compared to non-frail participants in each domain-specific outcome, except for immediate recall. Largest differences in slope were observed for CDT (difference = −0.12 (standard deviations) SD/year, 95%CI: −0.15, −0.08). By 2016, mean CDT scores for frail participants were 1.8 SD below the mean (95%CI: −1.99, −1.67); for non-frail participants, scores were 0.8 SD below the mean (95%CI: −0.89, −0.69). Associations differed by education for global cognitive function (P interaction < 0.001) and for each domain-specific outcome: CDT (P interaction < 0.001), orientation (P interaction < 0.001), immediate (P interaction < 0.001) and delayed (P interaction < 0.001) word recalls. Conclusion frailty is associated with lower levels and steeper declines in cognitive function, with strongest associations for executive function. These findings suggest that aetiologies are multifactorial, though primarily vascular related; further research into its association with dementia sub-types and related pathologies is critical. [ABSTRACT FROM AUTHOR]

Background: Frailty (physical frailty phenotype [PFP]) and its criteria (slow gait, weakness, weight loss, low activity, and exhaustion) are each associated with cognitive dysfunction. The extent to which the PFP is associated with cognition beyond that expected from its component parts remains uncertain.Method: We used the National Health and Aging Trends Study to quantify associations between PFP criteria and cognitive performance (level/change) using adjusted mixed effects models. We tested whether frailty was associated with excess cognitive vulnerability (synergistic/excess effects, Cohen's d) beyond criteria contributions by assessing interactions between each criterion and frailty.Results: Among 7439 community-dwelling older adults (mean age = 75.2 years) followed for a mean of 3.2 years (SE = 0.03), 14.1% were frail. The PFP and PFP criteria were all associated with lower baseline cognitive performance, among which slow gait (-0.31 SD, SE = 0.02) and frailty (-0.23 SD, SE = 0.02) were strongest. Only slow gait (-0.03 SD/year, SE = 0.01), frailty (-0.02 SD/year, SE = 0.01), weight loss (-0.02 SD/year, SE = 0.01), and weakness (-0.02 SD/year, SE = 0.01) were associated with cognitive decline. Frailty was associated with cognitive performance above and beyond each criterion (excess effects ranging from -0.07 SD [SE = -0.05] for slow gait to -0.23 SD [SE = 0.03] for weakness); the same was not true for cognitive decline. Slow gait was the only criterion associated with cognitive change among both frail and nonfrail participants (frail: Cohen's d/year = -0.03, SE = 0.01; nonfrail: Cohen's d/year = -0.02, SE = 0.01).Conclusions: PFP is an important frailty measure that is cross-sectionally associated with lower cognitive performance, but not with subsequent cognitive decline, above and beyond its criteria contributions. Further research into the construct of frailty as a "syndrome" correlated with cognition and other adverse outcomes is needed. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation (KT) candidates often present with multiple comorbidities. These patients also have a substantial burden of frailty, which is also associated with increased mortality. However, it is unknown if frailty is merely a surrogate for comorbidity, itself an independent domain of risk, or if frailty and comorbidity have differential effects. Better understanding the interplay between these 2 constructs will improve clinical decision making in KT candidates.Objective: To test whether comorbidity is equally associated with waitlist mortality among frail and nonfrail KT candidates and to test whether measuring both comorbidity burden and frailty improves mortality risk prediction.Methods: We studied 2,086 candidates on the KT waitlist (November 2009 - October 2017) in a multicenter cohort study, in whom frailty and comorbidity were measured at evaluation. We quantified the association between Charlson comorbidity index (CCI) adapted for end-stage renal disease and waitlist mortality using an adjusted Cox proportional hazards model and tested whether this association differed between frail and nonfrail candidates.Results: At evaluation, 18.1% of KT candidates were frail and 51% had a high comorbidity burden (CCI score ≥2). Candidates with a high comorbidity burden were at 1.38-fold (95% CI 1.01-1.89) increased risk of waitlist mortality. However, this association differed by frailty status (p for interaction = 0.01): among nonfrail candidates, a high comorbidity burden was associated with a 1.66-fold (95% CI 1.17-2.35) increased mortality risk; among frail candidates, here was no statistically significant association (HR 0.75, 95% CI 0.44-1.29). Adding this interaction between comorbidity and frailty to a mortality risk estimation model significantly improved prediction, increasing the c-statistic from 0.640 to 0.656 (p < 0.001).Conclusions: Nonfrail candidates with a high comorbidity burden at KT evaluation have an increased risk of waitlist mortality. Importantly, comorbidity is less of a concern in already high-risk patients who are frail. [ABSTRACT FROM AUTHOR]

Background: Fine particulate matter (particulate matter with diameter <2.5 µm [PM2.5]) is associated with CKD progression and may impact the health of patients living with kidney failure. While older (aged ≥65 years) adults are most vulnerable to the impact of PM2.5, it is unclear whether older patients on dialysis are at elevated risk of mortality when exposed to fine particulate matter.Methods: Older adults initiating dialysis (2010-2016) were identified from US Renal Data System (USRDS). PM2.5 concentrations were obtained from NASA's Socioeconomic Data and Application Center (SEDAC) Global Annual PM2.5 Grids. We investigated the association between PM2.5 and all-cause mortality using Cox proportional hazard models with linear splines [knot at the current Environmental Protection Agency (EPA) National Ambient Air Quality Standard for PM2.5 of 12 μg/m3] and robust variance.Results: For older dialysis patients who resided in areas with high PM2.5, a 10 μg/m3 increase in PM2.5 was associated with 1.16-fold (95% CI: 1.08-1.25) increased risk of mortality; furthermore, those who were female (aHR = 1.26, 95% CI: 1.13-1.42), Black (aHR = 1.31, 95% CI: 1.09-1.59), or had diabetes as a primary cause of kidney failure (aHR = 1.25, 95% CI: 1.13-1.38) were most vulnerable to high PM2.5. While the mortality risk associated with PM2.5 was stronger at higher levels (aHR = 1.19, 95% CI: 1.08-1.32), at lower levels (≤12 μg/m3), PM2.5 was significantly associated with mortality risk (aHR = 1.04, 95% CI: 1.00-1.07) among patients aged ≥75 years (Pslope difference = 0.006).Conclusions: Older adults initiating dialysis who resided in ZIP codes with PM2.5 levels >12 μg/m3 are at increased risk of mortality. Those aged >75 were at elevated risk even at levels below the EPA Standard for PM2.5. [ABSTRACT FROM AUTHOR]

Background: Physical frailty phenotype is characterized by decreased physiologic reserve to stressors and associated with poor outcomes, such as delirium and mortality, that may result from post-kidney transplant (KT) inflammation. Despite a hypothesized underlying pro-inflammatory state, conventional measures of frailty typically do not incorporate inflammatory biomarkers directly. Among KT candidates and recipients, we evaluated the inclusion of inflammatory biomarkers with traditional physical frailty phenotype components.Methods: Among 1154 KT candidates and recipients with measures of physical frailty phenotype and inflammation (interleukin 6 [IL6], tumor necrosis factor alpha [TNFα], C-reactive protein [CRP]) at 2 transplant centers (2009-2017), we evaluated construct validity of inflammatory-frailty using latent class analysis. Inflammatory-frailty measures combined 5 physical frailty phenotype components plus the addition of an individual inflammatory biomarkers, separately (highest tertiles) as a sixth component. We then used Kaplan-Meier methods and adjusted Cox proportional hazards to assess post-KT mortality risk by inflammatory-frailty (n = 378); Harrell's C-statistics assessed risk prediction (discrimination).Results: Based on fit criteria, a 2-class solution (frail vs nonfrail) for inflammatory-frailty was the best-fitting model. Five-year survival (frail vs nonfrail) was: 81% versus 93% (IL6-frailty), 87% versus 89% (CRP-frailty), and 83% versus 91% (TNFα-frailty). Mortality was 2.07-fold higher for IL6-frail recipients (95% CI: 1.03-4.19, p = .04); there were no associations between the mortality and the other inflammatory-frailty indices (TNFα-frail: 1.88, 95% CI: 0.95-3.74, p = .07; CRP-frail: 1.02, 95% CI: 0.52-2.03, p = .95). However, none of the frailty-inflammatory indices (all C-statistics = 0.71) improved post-KT mortality risk prediction over the physical frailty phenotype (C-statistics = 0.70).Conclusions: Measurement of IL6-frailty at transplantation can inform which patients should be targeted for pre-KT interventions. However, the traditional physical frailty phenotype is sufficient for post-KT mortality risk prediction. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: To obtain national and regional estimates of prevalence of frailty with or without cognitive impairment, and cognitive impairment with or without frailty among older adults in the United States, and to identify profiles of characteristics that distinguish their joint versus separate occurrence. DESIGN: Cross‐sectional. SETTING: Community or non–nursing home residential care settings. PARTICIPANTS: A U.S. nationally representative sample of 7,497 older adults aged 65 and older from the National Health and Aging Trends Study. MEASUREMENTS: Frailty was measured by the physical frailty phenotype. Cognitive impairment was assessed by cognitive performance testing of executive function and memory or by proxy reports. Multinomial logistic regression was used to identify profiles of demographic, socioeconomic, health, behavioral, and psychosocial characteristics that distinguish four subgroups: not‐frail and cognitively intact ("neither"), not‐frail and cognitively impaired ("Cog. only"), frail and cognitively intact ("frailty only"), and frail and cognitively impaired ("both"). RESULTS: The prevalence of "Cog. only," "frailty only," and "both" was 25.5%, 5.6%, and 8.7%, respectively. Individuals with"frailty only" had the highest prevalence of obesity, current smoking, comorbidity, lung disease, and history of surgery. The "both" group had the highest prevalence of dementia, depression, cardiovascular diseases, and disability. No significant differences were found between the "Cog. only" group and the "neither" group with respect to history of surgery and comorbidity burden. The prevalence of dementia in the "Cog. only" was less than half of that in the "both" group. CONCLUSION: The finding of sizable subgroups having physical frailty but not cognitive impairment, and vice versa, suggests that the two cannot be considered necessarily as antecedent or sequela of one another. The study provided empirical data supporting the prioritization of comorbidity, obesity, surgery history, and smoking status in clinical screening of frailty and cognitive impairment before formal diagnostic assessments. [ABSTRACT FROM AUTHOR]

Background Disability in general has been associated with poor outcomes in kidney transplant (KT) recipients. However, disability can be derived from various components, specifically visual, hearing, physical and walking impairments. Different impairments may compromise the patient through different mechanisms and might impact different aspects of KT outcomes. Methods In our prospective cohort study (June 2013–June 2017), 465 recipients reported hearing, visual, physical and walking impairments before KT. We used hybrid registry-augmented Cox regression, adjusting for confounders using the US KT population (Scientific Registry of Transplant Recipients, N  = 66 891), to assess the independent association between impairments and post-KT outcomes [death-censored graft failure (DCGF) and mortality]. Results In our cohort of 465 recipients, 31.6% reported one or more impairments (hearing 9.3%, visual 16.6%, physical 9.1%, walking 12.1%). Visual impairment was associated with a 3.36-fold [95% confidence interval (CI) 1.17–9.65] higher DCGF risk, however, hearing [2.77 (95% CI 0.78–9.82)], physical [0.67 (95% CI 0.08–3.35)] and walking [0.50 (95% CI 0.06–3.89)] impairments were not. Walking impairment was associated with a 3.13-fold (95% CI 1.32–7.48) higher mortality risk, however, visual [1.20 (95% CI 0.48–2.98)], hearing [1.01 (95% CI 0.29–3.47)] and physical [1.16 (95% CI 0.34–3.94)] impairments were not. Conclusions Impairments are common among KT recipients, yet only visual impairment and walking impairment are associated with adverse post-KT outcomes. Referring nephrologists and KT centers should identify recipients with visual and walking impairments who might benefit from targeted interventions pre-KT, additional supportive care and close post-KT monitoring. [ABSTRACT FROM AUTHOR]

Background: Frailty, originally characterized in community-dwelling older adults, is increasingly being studied and implemented for adult patients with end-stage kidney disease (ESKD) of all ages (>18 years). Frailty prevalence and manifestation are unclear in younger adults (18-64 years) with ESKD; differences likely exist based on whether the patients are treated with hemodialysis (HD) or kidney transplantation (KT).Methods: We leveraged 3 cohorts: 378 adults initiating HD (2008-2012), 4,304 adult KT candidates (2009-2019), and 1,396 KT recipients (2008-2019). The frailty phenotype was measured within 6 months of dialysis initiation, at KT evaluation, and KT admission. Prevalence of frailty and its components was estimated by age (≥65 vs. <65 years). A Wald test for interactions was used to test whether risk factors for frailty differed by age.Results: In all 3 cohorts, frailty prevalence was higher among older than younger adults (HD: 71.4 vs. 47.3%; candidates: 25.4 vs. 18.8%; recipients: 20.8 vs. 14.3%). In all cohorts, older patients were more likely to have slowness and weakness but less likely to report exhaustion. Among candidates, older age (odds ratio [OR] = 1.79, 95% CI: 1.47-2.17), non-Hispanic black race (OR = 1.30, 95% CI: 1.08-1.57), and dialysis type (HD vs. no dialysis: OR = 2.06, 95% CI: 1.61-2.64; peritoneal dialysis vs. no dialysis: OR = 1.78, 95% CI: 1.28-2.48) were associated with frailty prevalence, but sex and Hispanic ethnicity were not. These associations did not differ by age (pinteractions > 0.1). Similar results were observed for recipients and HD patients.Conclusions: Although frailty prevalence increases with age, younger patients have a high burden. Clinicians caring for this vulnerable population should recognize that younger patients may experience frailty and screen all age groups. [ABSTRACT FROM AUTHOR]

Background Approximately half of the patients who progress to end-stage kidney disease (ESKD) and undergo dialysis develop difficulties carrying out essential self-care activities, leading to institutionalization and mortality. It is unclear what percentage of kidney transplant (KT) candidates, a group of ESKD patients selected to be healthy enough to withstand transplantation, are functionally independent and whether independence is associated with better access to KT and reduced waitlist mortality. Methods We studied a prospective cohort of 3168 ESKD participants (January 2009 to June 2018) who self-reported functional independence in more basic self-care Activities of Daily Living (ADL) (needing help with eating, dressing, walking, grooming, toileting and bathing) and more complex instrumental ADL (IADL) (needing help using a phone, shopping, cooking, housework, washing, using transportation, managing medications and managing money). We estimated adjusted associations between functional independence (separately) and listing (Cox), waitlist mortality (competing risks) and transplant rates (Poisson). Results At KT evaluation, 92.4% were independent in ADLs, but only 68.5% were independent in IADLs. Functionally independent participants had a higher chance of listing for KT [ADL: adjusted hazard ratio (aHR) = 1.55, 95% confidence interval (CI) 1.30–1.87; IADL: aHR = 1.39, 95% CI 1.26–1.52]. Among KT candidates, ADL independence was associated with lower waitlist mortality risk [adjusted subdistribution HR (aSHR) = 0.66, 95% CI 0.44–0.98] and higher rate of KT [adjusted incidence rate ratio (aIRR) = 1.58, 95% CI 1.12–2.22]; the same was not observed for IADL independence (aSHR = 0.86, 95% CI 0.65–1.12; aIRR = 1.01, 95% CI 0.97–1.19). Conclusions Functional independence in more basic self-care ADL was associated with better KT access and lower waitlist mortality. Nephrologists, geriatricians and transplant surgeons should screen KT candidates for ADLs, and identify interventions to promote independence and improve waitlist outcomes. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQOL) reflects a patient's perceived disease burden, treatment effectiveness, and health status. Given the time burden and physiologic effects of hemodialysis, patients who spend dialysis time (9-15 h/week) physically or intellectually engaged may have better HRQOL. We characterized the intradialytic activities and explored their association with HRQOL.Methods: In a cross-sectional study of 431 hemodialysis patients, we ascertained kidney-disease-specific quality of life, measured frailty, and surveyed participants about their usual active intradialytic activities (reading, playing games, doing puzzles, chatting, or other) and passive intradialytic activities (watching TV or sleeping). We used adjusted ordered logistic regression to identify correlates of the activity index (the sum of active intradialytic activities) and adjusted linear regression to quantify the association between the activity index and physical-, mental-, and kidney-disease-specific HRQOL.Results: The 2 most common intradialytic activities were passive activities (watching TV = 87.9%; sleeping = 72.4%). Participants who were female (aOR 1.85, 95% CI 1.28-2.66; p = 0.001), nonfrail (aOR 1.70, 95% CI 1.06-2.70; p = 0.03), and nonsmokers (aOR 2.61, 95% CI 1.39-4.90; p = 0.003) had a higher intradialytic activity index after adjustment. Higher intradialytic activity index was associated with better mental- (0.83 points, 95% CI 0.04-1.62; p = 0.04) and kidney-disease-specific HRQOL (1.70 points, 95% CI 0.47-2.93; p = 0.007), but not physical HRQOL.Conclusions: Hemodialysis patients with more active intradialytic activities report better mental and kidney-disease-specific HRQOL. These results should be confirmed in a prospective study with a broader cohort of hemodialysis patients. Dialysis providers may consider offering patients with low levels of activity additional support and opportunities to engage in beneficial intradialytic activities. [ABSTRACT FROM AUTHOR]

Background: Frailty and cognitive impairment (CI) are associated and often coexist in older adults. Whether temporal patterns of occurrence reflect different etiologies remain unknown.Methods: Participants from the National Health and Aging Trends Study were assessed annually (2011-2016) for frailty (Fried's criteria) and CI (bottom quintile of clock drawing test or immediate and delayed recall; proxy-report of dementia diagnosis or AD8 ≥ 2). We used the Fine & Gray model to identify correlates of frailty onset before CI, CI onset before frailty, and frailty-CI co-occurrence, accounting for death as a competing risk.Results: Of 3,848 free of frailty, CI, and dementia at baseline, 2,183 (61.2%) developed neither frailty nor CI during the 5-year follow-up; 343 (8.3%) developed frailty first; 1,014 (24.4%) developed CI first; and 308 (6.0%) developed frailty-CI co-occurrence. Incident dementia, as a marker of underlying neuropathologies, was associated with greater likelihood of CI onset first (subdistribution hazard ratios [SHR] = 2.60, 95% confidence interval [ci] 2.09 to 3.24), and frailty-CI co-occurrence (SHR = 8.77, 95% ci 5.79 to 13.28), but lower likelihood of frailty onset first (SHR = 0.38, 95% ci 0.21 to 0.68). Number of comorbidities was only associated with frailty occurrence first (1 comorbidity: SHR = 2.51, 95% ci 1.15 to 5.47; 4+ comorbidities: SHR = 6.48, 95% ci 2.78 to 15.48).Conclusions: Different patterns of frailty and CI occurrence exist, and dementia-related pathologies and comorbidities may be important correlates of order of emergence, potentially reflecting different etiologies. Future investigation into relationships between these patterns and dementia subtypes and related pathologies is needed to elucidate etiologic pathways and to provide new targets for prevention, intervention, and risk screening. [ABSTRACT FROM AUTHOR]