Faculty Bibliography

Kidney transplantation (KT) experts did not support the use of subjective unintentional weight loss to measure shrinking in the physical frailty phenotype (PFP); a clinically feasible and predictive measure of shrinking is needed. To test whether unintentional weight loss could be replaced by an assessment of sarcopenia using existing CT scans, we performed a prospective cohort study of adult KT recipients with original PFP (oPFP) measured at admission (December 2008-February 2020). We ascertained sarcopenia by calculating skeletal muscle index from available, clinically obtained CTs within 1-year pre-KT (male < 50 cm² /m² ; female < 39 cm² /m² ) and combined it with the original four components to determine new PFP (nPFP) scores. Frailty was classified by frailty score: 0: non-frail; 1-2: pre-frail; ≥3: frail. Mortality and graft loss hazard ratios (HRs) were estimated using adjusted Cox proportional hazard models. Model discrimination was quantified using Harrell's C-statistic. Among 1113 recipients, 18.6% and 17.1% were frail by oPFP and nPFP, respectively. Compared to non-frail recipients, frail patients by either PFP had higher risks of mortality (oPFP HR = 1.67, 95% CI: 1.07-2.62, C = 0.710; nPFP HR = 1.68, 95% CI: 1.06-2.66, C = 0.710) and graft loss (oPFP HR = 1.67, 95% CI: 1.17-2.40, C = 0.631; nPFP HR = 1.66, 95% CI: 1.15-2.40, C = 0.634) with similar discriminations. oPFP and nPFP are equally useful in risk prediction for KT recipients; oPFP may aid in screening patients for pre-KT interventions, while nPFP may assist in nuanced clinical decision-making.

Background/UNASSIGNED:Posttransplant diabetes (PTD), a major complication after kidney transplantation (KT), is often attributable to immunosuppression. The risk of PTD may increase with more potent steroid maintenance and older recipient age. Methods/UNASSIGNED:Using United States Renal Data System data, we studied 12 488 adult first-time KT recipients (2010-2015) with no known pre-KT diabetes. We compared the risk of PTD among recipients who underwent early steroid withdrawal (ESW) versus continued steroid maintenance (CSM) using Cox regression with inverse probability weighting to adjust for confounding. We tested whether the risk of PTD resulting from ESW differed by recipient age (18-29, 30-54, and ≥55 y). Results/UNASSIGNED:). Conclusions/UNASSIGNED:The beneficial association of ESW with decreased PTD was more pronounced among recipients aged ≥55, supporting an age-specific assessment of the risk-benefit balance regarding ESW.

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.

UNLABELLED:The unplanned use of dual induction therapy with interleukin-2 receptor-blocking antibodies (IL2rAb) and antithymocyte globulin (ATG) may portend adverse outcomes. METHODS/UNASSIGNED:]). RESULTS/UNASSIGNED: < 0.0001). CONCLUSIONS/UNASSIGNED:Further research is needed to develop risk-prediction tools to further inform optimal, individualized induction protocols for kidney transplant recipients.

Purpose of Review/UNASSIGNED:To summarize the research on post-operative delirium among patients undergoing solid organ transplantation in efforts to improve recognition, evaluation, and management, as well as highlight areas for future research. Recent Findings/UNASSIGNED:Delirium is a common complication in patients with organ failure before and after undergoing solid organ transplant (range: 4.7-47%). However, it is frequently unrecognized and underdiagnosed-even among those closely monitored after major surgery-given that its manifestation is often variable and inconsistent. Delirium has multifactorial etiologies comprising of a complex mix of predisposing recipient, donor, and transplant factors, as well as intraoperative and perioperative factors. Evidence suggests that delirium risk increases with presence of a greater number of such risk factors, and can lead to adverse outcomes such as increased hospital length of stay, time in the ICU, time on mechanical ventilators, graft dysfunction, graft loss, and mortality. Though no trials have been conducted among transplant populations specifically, delirium has been shown to be preventable among hospitalized older adults generally. Multicomponent, primary prevention strategies designed to target multiple risk factors of delirium, such as cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration, have been identified as most effective. Whether these approaches translate to improvements in quality of life and long-term health outcomes among patients with organ failure before and after transplantation is yet to be determined. Summary/UNASSIGNED:Delirium is an important, common, yet potentially preventable complication among patients with organ failure. Future studies are needed to test the efficacy of multicomponent, primary prevention strategies on long-term health outcomes among these vulnerable populations.

PURPOSE OF REVIEW:Clinicians treating end-stage kidney disease (ESKD) and kidney transplant patients face unique challenges in their care because of the high burden of frailty in these patients. Frailty has gained significant attention by medical and surgical specialties for risk stratification in the past decades. This review highlights the importance of measuring frailty in kidney transplant candidates and recipients. RECENT FINDINGS:Emerging data support that frailty is present even at younger ages among patients undergoing dialysis, transplant evaluation, or transplantation. It is estimated that 18.8% of younger (18-64 years) candidates, 25.2% of older (≥65 years) candidates, 14.3% of younger recipients, and 20.8% of older recipients are frail. Additionally, frailty is dynamic and subject to change pretransplantation and posttransplantation. Although many patients and clinicians are aware of the importance of measuring frailty, further studies addressing the need for interventions to reduce frailty burden are needed. SUMMARY:Frailty is independently associated with many adverse outcomes in ESKD and kidney transplant populations. Given the growing number of ESKD and kidney transplant patients, it is pivotal to expand the utility of frailty measurement in clinical practice, recognize the burden of frailty, and identify appropriate interventions to mitigate the adverse effects of frailty.

Rationale & Objective/UNASSIGNED:Social support in older adults with chronic kidney disease (CKD) is a potentially modifiable factor that may affect important clinical outcomes such as health-related quality of life, cognitive function, and frailty. However, limited data about the effects of social support in older patients with non-dialysis-dependent CKD exist. Our objective was to evaluate the association of social support with health-related quality of life, cognitive function, and frailty in older adults with CKD. Study Design/UNASSIGNED:Cross-sectional analysis of a prospective cohort study. Setting & Population/UNASSIGNED:1,851 participants older than 65 years with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Exposure/UNASSIGNED:Social support (Lubben Social Network Scale [LSNS]). Outcomess/UNASSIGNED:Health-related quality of life (Kidney Disease Quality of Life-36), cognitive function (Modified Mini-Mental State Examination, Trail Making Test A & B, and Buschke Selective Reminder Tests), and frailty (modified Fried frailty criteria). Analytic Approach/UNASSIGNED:Multivariable, linear, and logistic regression to determine the association between social support and health-related quality of life, cognitive function, and frailty. Results/UNASSIGNED:Low social support, defined as LSNS score < 12, was present in 22% of participants. On multivariable analysis, higher social support was associated with higher health-related quality of life (β coefficient per 1-SD increase in LSNS score; burden subscale, 2.57 (95% CI, 1.57-3.56); effects subscale, 2.21 (95% CI, 1.52-2.9); symptoms subscale, 1.64 (95% CI, 0.88-2.41); mental health composite subscale, 1.91 (95% CI, 1.40-2.43); and physical health composite score, 0.64 (95% CI, 0.03-1.24)). Higher social support was associated with better cognitive function (β coefficient per 1-SD increase in LSNS score; Modified Mini-Mental State Examination, 0.81 (95% CI, 0.44 to 1.19); Trail Making Test A & B, -2.53 (95% CI, -4.29 to -0.76) and -6.53 (95% CI, -10.07 to -2.99), respectively; Buschke Selective Reminder Test 1, 2, and 3, 0.19 (95% CI, 0.07 to 0.30); 1.59 (95% CI, 0.96 to 2.22); and 0.40 (95% CI, 0.23 to 0.56), respectively. Higher social support was associated with higher likelihood of being nonfrail (OR, 1.77; 95% CI per 1-SD higher LSNS score, 1.24-2.53). Limitations/UNASSIGNED:Conclusions about causality cannot be drawn from an observational cross-sectional study. Conclusions/UNASSIGNED:In older patients with CKD, higher social support was associated with higher health-related quality of life and cognitive function and less frailty.

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 (Pinteraction < 0.001) and for each domain-specific outcome: CDT (Pinteraction < 0.001), orientation (Pinteraction < 0.001), immediate (Pinteraction < 0.001) and delayed (Pinteraction < 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.

Introduction/UNASSIGNED:Defining the role of exercise in chronic kidney disease (CKD) is a top research priority for people with CKD. We aimed to achieve consensus on specific research priorities in exercise and CKD among an international panel of stakeholders. Methods/UNASSIGNED:Using the Delphi method, patients/caregivers, researchers, clinicians, and policymakers submitted their top research priorities in round 1 and ranked their importance in rounds 2 and 3 using a 9-point Likert scale. The mean, median, and proportion of scores ranked 7 to 9 were calculated. Consensus was defined as priorities that scored above the overall mean and median score within each stakeholder panel. Qualitative description was used to understand participants' rankings. Results/UNASSIGNED:Seventy participants (78% response) completed round 1: 15 (21.4%) clinicians, 33 (47.1%) researchers, 13 (18.6%) policymakers, and 9 (12.9%) patients; (85.7%) completed round 3. The top research priorities were defining exercise-related outcomes meaningful to patients, identifying patients' motivation and perspective towards exercise, understanding the effect of exercise on the risk of institutionalization, mortality, and mobility, and understanding the effect of pre- and post-transplant exercise on postoperative recovery. Themes from the qualitative analysis were individualization, personal experience, and holistic approach to exercise (patients), the need to address common clinical problems (clinicians), developing targeted interventions (researchers), and the importance of evidence-based development versus implementation (policymakers). Conclusions/UNASSIGNED:Preventing physical disability was a common priority. Policymakers emphasized that more efficacy studies were needed. Other panels expressed the need for holistic and targeted exercise interventions and for outcomes that address common clinical problems.