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      Frailty and Changes in Cognitive Function after Kidney Transplantation

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          Abstract

          Frailty is a predictor of adverse outcomes in kidney transplant populations. Although restoration of kidney function after transplant generally improves cognitive function, it seems plausible that, in frail individuals, stressors related to surgery and immunosuppression might mitigate short-term cognitive improvement and contribute to possible subsequent decline. The authors found significantly lower pretransplant cognitive scores in frail kidney transplant recipients compared with nonfrail recipients. Although both groups showed cognitive improvement by 3 months post-transplant, cognitive function plateaued for nonfrail recipients between 1 and 4 years after transplant and declined for frail recipients. By 4 years post-transplant, cognitive scores were significantly lower among frail versus nonfrail recipients. Transplant centers are encouraged to apply available evidence-based strategies to reduce risk of cognitive impairment among frail transplant recipients. Restoration of kidney function after kidney transplant generally improves cognitive function. It is unclear whether frail recipients, with higher susceptibility to surgical stressors, achieve such post-transplant cognitive improvements or whether they experience subsequent cognitive decline as they age with a functioning graft. In this two-center cohort study, we assessed pretransplant frailty (Fried physical frailty phenotype) and cognitive function (Modified Mini-Mental State Examination) in adult kidney transplant recipients. To investigate potential short- and medium-term effects of frailty on post-transplant cognitive trajectories, we measured cognitive function up to 4 years post-transplant. Using an adjusted mixed effects model with a random slope (time) and intercept (person), we characterized post-transplant cognitive trajectories by pretransplant frailty, accounting for nonlinear trajectories. Of 665 recipients (mean age 52.0 years) followed for a median of 1.5 years, 15.0% were frail. After adjustment, pretransplant cognitive scores were significantly lower among frail patients compared with nonfrail patients (89.0 versus 90.8 points). By 3 months post-transplant, cognitive performance improved for both frail (slope =0.22 points per week) and nonfrail (slope =0.14 points per week) recipients. Between 1 and 4 years post-transplant, improvements plateaued among nonfrail recipients (slope =0.005 points per week), whereas cognitive function declined among frail recipients (slope =−0.04 points per week). At 4 years post-transplant, cognitive scores were 5.8 points lower for frail recipients compared with nonfrail recipients. On average, both frail and nonfrail recipients experience short-term cognitive improvement post-transplant. However, frailty is associated with medium-term cognitive decline post-transplant. Interventions to prevent cognitive decline among frail recipients should be identified.

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          Most cited references43

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          Estimation of Relationships for Limited Dependent Variables

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            Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments.

            The medical syndrome of frailty is widely recognized, yet debate remains over how best to measure it in clinical and research settings. This study reviewed the frailty-related research literature by (a) comprehensively cataloging the wide array of instruments that have been utilized to measure frailty, and (b) systematically categorizing the different purposes and contexts of use for frailty instruments frequently cited in the research literature. We identified 67 frailty instruments total; of these, nine were highly-cited (≥ 200 citations). We randomly sampled and reviewed 545 English-language articles citing at least one highly-cited instrument. We estimated the total number of uses, and classified use into eight categories: risk assessment for adverse health outcomes (31% of all uses); etiological studies of frailty (22%); methodology studies (14%); biomarker studies (12%); inclusion/exclusion criteria (10%); estimating prevalence as primary goal (5%); clinical decision-making (2%); and interventional targeting (2%). The most common assessment context was observational studies of older community-dwelling adults. Physical Frailty Phenotype was the most used frailty instrument in the research literature, followed by the Deficit Accumulation Index and the Vulnerable Elders Survey. This study provides an empirical evaluation of the current uses of frailty instruments, which may be important to consider when selecting instruments for clinical or research purposes. We recommend careful consideration in the selection of a frailty instrument based on the intended purpose, domains captured, and how the instrument has been used in the past. Continued efforts are needed to study the validity and feasibility of these instruments.
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              Adapting the Charlson Comorbidity Index for use in patients with ESRD.

              Accurate prediction of survival for patients with end-stage renal disease (ESRD) and multiple comorbid conditions is difficult. In nondialysis patients, the Charlson Comorbidity Index has been used to adjust for comorbidity. The purpose of this study is to assess the validity of the Charlson index in incident dialysis patients and modify the index for use specifically in this patient population. Subjects included all incident hemodialysis and peritoneal dialysis patients starting dialysis therapy between July 1, 1999, and November 30, 2000. These 237 patients formed a cohort from which new integer weights for Charlson comorbidities were derived using Cox proportional hazards modeling. Performance of the original Charlson index and the new ESRD comorbidity index were compared using Kaplan-Meier survival curves, change in likelihood ratio, and the c statistic. After multivariate analysis and conversion of hazard ratios to index weights, only 6 of the original 18 Charlson variables were assigned the same weight and 6 variables were assigned a weight higher than in the original Charlson index. Using Kaplan-Meier survival curves, we found that both the original Charlson index and the new ESRD comorbidity index were associated with and able to describe a wide range of survival. However, the new study-specific index had better validated performance, indicated by a greater change in the likelihood ratio test and higher c statistic. This study indicates that the original Charlson index is a valid tool to assess comorbidity and predict survival in patients with ESRD. However, our modified ESRD comorbidity index had slightly better performance characteristics in this population.
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                Author and article information

                Journal
                Journal of the American Society of Nephrology
                JASN
                American Society of Nephrology (ASN)
                1046-6673
                1533-3450
                January 31 2019
                February 2019
                February 2019
                January 24 2019
                : 30
                : 2
                : 336-345
                Article
                10.1681/ASN.2018070726
                6362628
                30679381
                fc30a55c-65c3-494b-8ad3-2207facf79b7
                © 2019
                History

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