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Frailty and Changes in Cognitive Function after Kidney Transplantation.

ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Chu NM

PROVIDER: S-EPMC6362628 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Frailty and Changes in Cognitive Function after Kidney Transplantation.

Chu Nadia M NM Gross Alden L AL Shaffer Ashton A AA Haugen Christine E CE Norman Silas P SP Xue Qian-Li QL Sharrett A Richey AR Carlson Michelle C MC Bandeen-Roche Karen K Segev Dorry L DL McAdams-DeMarco Mara A MA

Journal of the American Society of Nephrology : JASN 20190124 2

<h4>Background</h4>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.<h4>Methods</h4>In this two-center cohort study, we assessed pretransplant frailty (Fried physical frailty phenotype) and cognitive function (Modified M ...[more]

PMID: 30679381

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Project description:Background and objectivesKidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.Design, setting, participants, & measurementsCHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.ResultsThe mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ≥90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.ConclusionsIn community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

Project description:Rationale & objectiveIntact cognition is generally a prerequisite for navigating through and completing evaluation for kidney transplantation. Despite kidney transplantation being contraindicated for those with severe dementia, screening for more mild forms of cognitive impairment before referral is rare. Candidates may have unrecognized cognitive impairment, which may prolong evaluation, elevate mortality risk, and hinder access to kidney transplantation. We estimated the burden of cognitive impairment and its association with access to kidney transplantation and waitlist mortality.Study designProspective cohort study.Setting & participants3,630 participants (January 2009 to June 2018) with cognitive function measured (by the Modified Mini-Mental State Examination [3MS]) at kidney transplantation evaluation at 1 of 2 transplantation centers.PredictorsCognitive impairment (3MS score<80).OutcomesListing, waitlist mortality, and kidney transplantation.Analytical approachWe estimated the adjusted chance of listing (Cox regression), risk for waitlist mortality (competing-risks regression), and kidney transplantation rate (Poisson regression) by cognitive impairment. Given potential differences in cause of cognitive impairment among those with and without diabetes, we tested whether these associations differed by diabetes status using a Wald test.ResultsAt evaluation, 6.4% of participants had cognitive impairment, which was independently associated with 25% lower chance of listing (adjusted HR, 0.75; 95% CI, 0.61-0.91); this association did not differ by diabetes status (Pinteraction=0.07). There was a nominal difference by diabetes status for the association between cognitive impairment and kidney transplantation rate (Pinteraction=0.05), while the association between cognitive impairment and waitlist mortality differed by diabetes status kidney transplantation rates (Pinteraction=0.02). Among candidates without diabetes, those with cognitive impairment were at 2.47 (95% CI, 1.31-4.66) times greater risk for waitlist mortality; cognitive impairment was not associated with this outcome among candidates with diabetes.LimitationsSingle measure of cognitive impairment.ConclusionsCognitive impairment is associated with a lower chance of being placed on the waitlist, and among patients without diabetes, with increased mortality on the waitlist. Future studies should investigate whether implementation of screening for cognitive impairment improves these outcomes.

Project description:BackgroundPhysical 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.MethodsAmong 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).ResultsBased 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).ConclusionsMeasurement 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.

Project description:Background and objectivesOver the past decade, the management of CKD-mineral and bone disorder has changed substantially, altering the pattern of bone disease in CKD. We aimed to evaluate the natural history of kidney bone disease in contemporary kidney transplant recipients and patients on dialysis.Design, settings, participants, & measurementsSixty one patients on dialysis who were referred to kidney transplantation participated in this prospective cohort study during November 2009 and December 2010. We performed baseline bone biopsies while the patients were on dialysis and repeated the procedure in 56 patients at 2 years after kidney transplantation or 2 years after baseline if transplantation was not performed. Measurements of mineral metabolism and bone turnover, as well as dual energy x-ray absorptiometry scans, were obtained concurrently.ResultsA total of 37 out of 56 participants received a kidney transplant, of which 27 underwent successful repeat bone biopsy. The proportion of patients with high bone turnover declined from 63% at baseline to 19% at 2 years after kidney transplantation, whereas the proportion of those with low bone turnover increased from 26% to 52%. Of 19 participants remaining on dialysis after 2 years, 13 underwent successful repeat biopsy. The proportion of patients remaining on dialysis with high bone turnover decreased from 69% to 31%, and low bone turnover increased from 8% to 38%. Abnormal bone mineralization increased in transplant recipients from 33% to 44%, but decreased in patients remaining on dialysis from 46% to 15%. Trabecular bone volume showed little change after transplantation, but low bone volume increased in patients remaining on dialysis. Bone mineral density did not correlate with histomorphometric findings.ConclusionsBone turnover decreased over time both in patients remaining on dialysis and in kidney transplant recipients. Bone mineral density and bone biomarkers were not associated with bone metabolism changes detected in bone biopsy specimens.

Dataset Information

Frailty and Changes in Cognitive Function after Kidney Transplantation.

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Frailty and Changes in Cognitive Function after Kidney Transplantation.

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