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Frailty is a multisystem syndrome of decreased physiologic reserve that has been shown to strongly and independently predict morbidity and mortality. Frailty is prevalent in patients living with kidney disease and occurs earlier in individuals with kidney disease as compared to the general population. In this comprehensive review, we examine clinical and research applications of frailty in kidney disease populations. Specifically, we clarify the definition of frailty and address common misconceptions, review the mechanisms and epidemiology of frailty in kidney disease, discuss challenges and limitations in frailty measurement, and provide updated evidence related to risk factors for frailty, its associated adverse outcomes, and interventions. We further add to the literature in this topic by highlighting the potential applications of frailty measurement in the care of patients with kidney disease and conclude with our recommendations for future research related to this important syndrome., (Published by Elsevier Inc.)

Background: Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD., Methods: Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD., Results: Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen's d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (p interactions  > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p [likelihood ratio test]  < 0.001) but not cognitive impairment., Conclusions: Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD., (© 2024. The Author(s).)

Background: Frailty is present in ≥50% of older adults receiving dialysis. Our objective was to a develop an administrative data-based frailty index and assess the frailty index's predictive validity for mortality and future hospitalizations., Methods: We used United States Renal Data System data to establish two cohorts of adults aged ≥65 years, initiating dialysis in 2013 and in 2017. Using the 2013 cohort (development dataset), we applied the deficit accumulation index approach to develop a frailty index. Adjusting for age and sex, we assessed the extent to which the frailty index predicts the hazard of time until death and time until first hospitalization over 12 months. We assessed the Harrell's C-statistic of the frailty index, a comorbidity index, and jointly. The 2017 cohort was used as a validation dataset., Results: Using the 2013 cohort ( n =20,974), we identified 53 deficits for the frailty index across seven domains: disabilities, diseases, equipment, procedures, signs, tests, and unclassified. Among those with ≥1 deficit, the mean (SD) frailty index was 0.30 (0.13), range 0.02-0.72. Over 12 months, 18% ( n =3842) died, and 55% ( n =11,493) experienced a hospitalization. Adjusted hazard ratios for each 0.1-point increase in frailty index in models of time to death and time to first hospitalization were 1.41 (95% confidence interval, 1.37 to 1.44) and 1.33 (95% confidence interval, 1.31 to 1.35), respectively. For mortality, C-statistics for frailty index, comorbidity index, and both indices were 0.65, 0.65, and 0.66, respectively. For hospitalization, C-statistics for frailty index, comorbidity index, and both indices were 0.61, 0.60, and 0.61, respectively. Data from the 2017 cohort were similar., Conclusions: We developed a novel frailty index for older adults receiving dialysis. Further studies are needed to improve on this frailty index and validate its use for clinical and research applications., Competing Interests: C. Colón-Emeric reports having consultancy agreements and an advisory or leadership role with Amgen and Novartis; reports receiving research funding from UCB Pharma; and reports having patents or royalties as Co-inventor 2 use patents for bisphonate indication in cardiovascular diseases. D.H. Kim reports having consultancy agreements with Alosa Health and VillageMD. J.F. Pendergast reports receiving research funding from Dialysis Centers, Inc.; and reports receiving honoraria from the National Institutes of Health National Institute on Aging/National Institute of Mental Health Advanced Research Institute for training junior scholars to get their first R01 (US$2000 for 3 days of mentoring). J.J. Scialla reports having an advisory or leadership role as Deputy Editor, American Journal of Kidney Diseases. L.E. Boulware reports having an advisory or leadership role with the Association for Clinical and Translational Science, Journal of the American Medical Association Editorial Board, Journal of the American Medical Association Network Online Editorial Board, and the Robert Wood Johnson Clinical Scholars National Advisory Committee. P.L. Ephraim reports having consultancy agreements with Stony Run Consulting. R. Hall reports having consultancy agreements with Bayer, Reata Pharmaceuticals, Otsuka, Travere Pharmaceuticals, and United Health Group; and reports having an advisory or leadership role with the CJASN Editorial Board and the Journal of the American Geriatrics Society Editorial Board. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

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., (© 2022 The Author(s). Published by S. Karger AG, Basel.)