Apathy Symptoms, Physical and Cognitive Function, Health-Related Quality of Life, and Mortality in Older Patients With CKD: A Longitudinal Observational Study.

RATIONALE & OBJECTIVE: Apathy reflects diminished motivation, goal-directed behavior, and emotions, as well as less engagement in social interactions. Apathy overlaps with depression and is associated with cognitive decline. In the older individuals with chronic kidney disease (CKD), both depression and cognitive impairments are common, but apathy symptoms have been underreported. We investigated the occurrence of apathy symptoms and their associations with physical and cognitive functioning, health-related quality of life (HRQoL), and mortality in older patients with CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 180 outpatients aged≥65 years with estimated glomerular filtration rate≤20mL/min/1.73m2 from 5 Dutch nephrology centers. EXPOSURE: Apathy symptoms at baseline were considered present when a Geriatric Depression Scale's 3-item apathy subscale score was≥2 points. OUTCOME: Physical and cognitive functioning, HRQoL (assessed in annual geriatric assessments), and 4-year mortality. ANALYTICAL APPROACH: Linear regression for cross-sectional associations, linear regression models for longitudinal associations, and Cox regression models for mortality over 4 years of observation. RESULTS: Apathy symptoms were present in 64 patients (36%; 67% men; median age 75.5 years), of whom 32 (50%) had no depressive symptoms. At baseline, the presence of apathy symptoms was associated with significantly more frailty, more functional dependence, less physical capacity, lower visuoconstructive performance, worse delayed recall, and lower HRQoL scores. The presence of apathy symptoms at baseline was also associated with a higher mortality risk (hazard ratio, 2.3 [95% CI, 1.3-4.2], P=0.005 adjusted for age, sex, and high education level), but not with changes in physical and cognitive functioning or HRQoL during the follow-up period. LIMITATIONS: Risk of selection bias and residual confounding. CONCLUSIONS: Apathy symptoms were highly prevalent and associated with concurrent lower physical and cognitive status, lower HRQoL, and increased mortality. These findings highlight apathy as a potentially important clinical phenotype in older CKD patients. PLAIN-LANGUAGE SUMMARY: We observed that older kidney patients often present apathy symptoms, such as less motivation, fewer goal-directed behaviors, fewer emotions, and less social engagement. Prior research has not extensively described apathy in kidney disease. We investigated the link between apathy symptoms and poor outcomes. We measured physical functioning, cognitive functioning, and quality of life. We learned that one-third of our older kidney patients showed symptoms of apathy, only half of whom had symptoms of depression. Patients with apathy symptoms showed lower quality of life and lower physical and cognitive performance. They also had a higher risk of death. These findings highlight the need for awareness of apathy symptoms in older kidney patients.

Circulating angiopoietin-2 and angiogenic microRNAs associate with cerebral small vessel disease and cognitive decline in older patients reaching end-stage renal disease.

BACKGROUND: The prevalence of end-stage renal disease (ESRD) is increasing worldwide, with the majority of new ESRD cases diagnosed in patients >60 years of age. These older patients are at increased risk for impaired cognitive functioning, potentially through cerebral small vessel disease (SVD). Novel markers of vascular integrity may be of clinical value for identifying patients at high risk for cognitive impairment. METHODS: We aimed to associate the levels of angiopoietin-2 (Ang-2), asymmetric dimethylarginine and a selection of eight circulating angiogenic microRNAs (miRNAs) with SVD and cognitive impairment in older patients reaching ESRD that did not yet initiate renal replacement therapy (n = 129; mean age 75.3 years, mean eGFR 16.4 mL/min). We assessed brain magnetic resonance imaging changes of SVD (white matter hyperintensity volume, microbleeds and the presence of lacunes) and measures of cognition in domains of memory, psychomotor speed and executive function in a neuropsychological test battery. RESULTS: Older patients reaching ESRD showed an unfavourable angiogenic profile, as indicated by aberrant levels of Ang-2 and five angiogenic miRNAs (miR-27a, miR-126, miR-132, miR-223 and miR-326), compared with healthy persons and patients with diabetic nephropathy. Moreover, Ang-2 was associated with SVD and with the domains of psychomotor speed and executive function, while miR-223 and miR-29a were associated with memory function. CONCLUSIONS: Taken together, these novel angiogenic markers might serve to identify older patients with ESRD at risk of cognitive decline, as well as provide insights into the underlying (vascular) pathophysiology.

Perspectives and experiences of patients and healthcare professionals with geriatric assessment in chronic kidney disease: a qualitative study.

BACKGROUND: Older patients with end-stage kidney disease (ESKD) often live with unidentified frailty and multimorbidity. Despite guideline recommendations, geriatric assessment is not part of standard clinical care, resulting in a missed opportunity to enhance (clinical) outcomes including quality of life in these patients. To develop routine geriatric assessment programs for patients approaching ESKD, it is crucial to understand patients' and professionals' experiences with and perspectives about the benefits, facilitators and barriers for geriatric assessment. METHODS: In this qualitative study, semi-structured focus group discussions were conducted with ESKD patients, caregivers and professionals. Participants were purposively sampled from three Dutch hospital-based study- and routine care initiatives involving geriatric assessment for (pre-)ESKD care. Transcripts were analysed inductively using thematic analysis. RESULTS: In six focus-groups, participants (n = 47) demonstrated four major themes: (1) Perceived characteristics of the older (pre)ESKD patient group. Patients and professionals recognized increased vulnerability and (cognitive) comorbidity, which is often unrelated to calendar age. Both believed that often patients are in need of additional support in various geriatric domains. (2) Experiences with geriatric assessment. Patients regarded the content and the time spent on the geriatric assessment predominantly positive. Professionals emphasized that assessment creates awareness among the whole treatment team for cognitive and social problems, shifting the focus from mainly somatic to multidimensional problems. Outcomes of geriatric assessment were observed to enhance a dialogue on suitability of treatment options, (re)adjust treatment and provide/seek additional (social) support. (3) Barriers and facilitators for implementation of geriatric assessment in routine care. Discussed barriers included lack of communication about goals and interpretation of geriatric assessment, burden for patients, illiteracy, and organizational aspects. Major facilitators are good multidisciplinary cooperation, involvement of geriatrics and multidisciplinary team meetings. (4) Desired characteristics of a suitable geriatric assessment concerned the scope and use of tests and timing of assessment. CONCLUSIONS: Patients and professionals were positive about using geriatric assessment in routine nephrology care. Implementation seems achievable, once barriers are overcome and facilitators are endorsed. Geriatric assessment in routine care appears promising to improve (clinical) outcomes in patients approaching ESKD.

Patterns and characteristics of cognitive functioning in older patients approaching end stage kidney disease, the COPE-study.

BACKGROUND: The prevalence of impaired cognitive functioning in older patients with end stage kidney disease (ESKD) is high. We aim to describe patterns of memory, executive function or psychomotor speed and to identify nephrologic, geriatric and neuroradiologic characteristics associated with cognitive impairment in older patients approaching ESKD who have not yet started with renal replacement therapy (RRT). METHODS: The COPE-study (Cognitive Decline in Older Patients with ESRD) is a prospective cohort study including 157 participants aged 65 years and older approaching ESKD (eGFR ≤20 ml/min/1.73 m2) prior to starting with RRT. In addition to routinely collected clinical parameters related to ESKD, such as vascular disease burden and parameters of metabolic disturbance, patients received a full geriatric assessment, including extensive neuropsychological testing. In a subgroup of patients (n = 93) a brain MRI was performed. RESULTS: The median age was 75.3 years. Compared to the normative data of neuropsychological testing participants memory performance was in the 24th percentile, executive function in the 18th percentile and psychomotor speed in the 20th percentile. Independent associated characteristics of impairment in memory, executive and psychomotor speed were high age, low educational level and low functional status (all p-values < 0.003). A history of vascular disease (p = 0.007) and more white matter hyperintensities on brain MRI (p = 0.013) were associated with a lower psychomotor speed. CONCLUSION: Older patients approaching ESKD have a high prevalence of impaired memory, executive function and psychomotor speed. The patterns of cognitive impairment and brain changes on MRI are suggestive of vascular cognitive impairment. These findings could be of potentially added value in the decision-making process concerning patients with ESKD.

Geriatric Assessment in CKD Care: An Implementation Study.

Rationale & Objective: Older people with progressive chronic kidney disease (CKD) have complex health care needs. Geriatric evaluation preceding decision making for kidney replacement is recommended in guidelines, but implementation is lacking in routine care. We aimed to evaluate implementation of geriatric assessment in CKD care. Study Design: Mixed methods implementation study. Setting & Participants: Dutch nephrology centers were approached for implementation of geriatric assessment in patients aged ≥70 years and with an estimated glomerular filtration rate of ≤20 mL/min/1.73 m2. Quality Improvement Activities/Exposure: We implemented a consensus-based nephrology-tailored geriatric assessment: a patient questionnaire and professionally administered test set comprising 16 instruments covering functional, cognitive, psychosocial, and somatic domains and patient-reported outcome measures. Outcomes: We aimed for implementation in 10 centers and 200 patients. Implementation was evaluated by (i) perceived enablers and barriers of implementation, including integration in work routines (Normalization Measure Development Tool) and (ii) relevance of the instruments to routine care for the target population. Analytical Approach: Variations in implementation practices were described based on field notes. The postimplementation survey among health care professionals was analyzed descriptively, using an explanatory qualitative approach for open-ended questions. Results: Geriatric assessment was implemented in 10 centers among 191 patients. Survey respondents (n = 71, 88% response rate) identified determinants that facilitated implementation, ie, multidisciplinary collaboration (with geriatricians) -meetings and reports and execution of assessments by nurses. Barriers to implementation were patient illiteracy or language barrier, time constraints, and patient burden. Professionals considered geriatric assessment sufficiently integrated into work routines (mean, 6.7/10 ± 2.0 [SD]) but also subject to improvement. Likewise, the relevance of geriatric assessment for routine care was scored as 7.8/10 ± 1.2. The Clinical Frailty Score and Montreal Cognitive Assessment were perceived as the most relevant instruments. Limitations: Selection bias of interventions' early adopters may limit generalizability. Conclusions: Geriatric assessment could successfully be integrated in CKD care and was perceived relevant to health care professionals.

The number of older persons with kidney failure is increasing, many of whom have cognitive decline or are dependent on others for daily life tasks. These problems are often overlooked but relevant for future treatment choices, and they affect quality of life. We asked 10 health care centers to use tests and questionnaires to identify these issues, thus being able to offer additional support. We learned that it is possible to use these assessments in practice and that professionals found them relevant. Collaboration with geriatric departments was perceived valuable. However, there are also challenges, such as not having enough time and personnel and burden to patients. Understanding these possibilities and challenges is crucial for improving care for older patients with kidney failure.

Nephrology-tailored geriatric assessment as decision-making tool in kidney failure.

BACKGROUND: Dialysis might not benefit all older patients with kidney failure, particularly those with multimorbid conditions and frailty. Patients' and healthcare professionals' awareness of the presence of geriatric impairments could improve outcomes by tailoring treatment plans and decisions for individual patients. OBJECTIVE: We aimed to explore the perspectives of patients and healthcare professionals on nephrology-tailored geriatric assessment to fuel decision-making for treatment choices in older patients with kidney failure. DESIGN: In an exploratory qualitative study using focus groups, participants discussed perspectives on the use and value of nephrology-tailored geriatric assessment for the decision-making process to start or forego dialysis. PARTICIPANTS AND MEASUREMENTS: Patients (n = 18) with kidney failure, caregivers (n = 4), and professionals (n = 25) were purposively sampled from 10 hospitals. Interviews were audio-recorded, transcribed verbatim and inductively analysed using thematic analysis. RESULTS: Three main themes emerged that supported or impeded decision-making in kidney failure: (1) patient psycho-social situation; (2) patient-related factors on modality choice; (3) organisation of health care. Patients reported feeling vulnerable due to multiple chronic conditions, old age, experienced losses in life and their willingness to trade longevity for quality of life. Professionals recognised the added value of nephrology-tailored geriatric assessment in three major themes: (i) facilitating continual holistic assessment, (ii) filling the knowledge gap, and (iii) uncovering important patient characteristics. CONCLUSIONS: nephrology-tailored geriatric assessment was perceived as a valuable tool to identify geriatric impairments in older patients with kidney failure. Integration of its outcomes can facilitate a more holistic approach to inform choices and decisions about kidney replacement therapy.

Circulating miRNAs and Vascular Injury Markers Associate with Cardiovascular Function in Older Patients Reaching End-Stage Kidney Disease.

The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from 'The Cognitive decline in Older Patients with End stage renal disease' (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology.

Design of a consensus-based geriatric assessment tailored for older chronic kidney disease patients: results of a pragmatic approach.

PURPOSE: Unidentified cognitive decline and other geriatric impairments are prevalent in older patients with advanced chronic kidney disease (CKD). Despite guideline recommendation of geriatric evaluation, routine geriatric assessment is not common in these patients. While high burden of vascular disease and existing pre-dialysis care pathways mandate a tailored geriatric assessment, no consensus exists on which instruments are most suitable in this population to identify geriatric impairments. Therefore, the aim of this study was to propose a geriatric assessment, based on multidisciplinary consensus, to routinely identify major geriatric impairments in older people with advanced CKD. METHODS: A pragmatic approach was chosen, which included focus groups, literature review, inventory of current practices, an expert consensus meeting, and pilot testing. In preparation of the consensus meeting, we composed a project team and an expert panel (n = 33), drafted selection criteria for the selection of instruments, and assessed potential instruments for the geriatric assessment. RESULTS: Selection criteria related to general geriatric domains, clinical relevance, feasibility, and duration of the assessment. The consensus-assessment contains instruments in functional, cognitive, psychological, somatic, patient preferences, nutritional status, and social domains. Administration of (seven) patient questionnaires and (ten) professional-administered instruments, by nurse (practitioners), takes estimated 20 and 40 min, respectively. Results are discussed in a multidisciplinary meeting including at least nephrology and geriatric expertise, informing nephrology treatment decisions, and follow-up interventions among which comprehensive geriatric assessment. CONCLUSION: This first multidisciplinary consensus on nephrology-tailored geriatric assessment intent to benefit clinical care and enhance research comparability for older patients with advanced CKD.

Optimal predialysis care.

Management of severe chronic kidney disease (CKD) involves dealing with medical, nursing and psychosocial problems and therefore warrants support from a multidisciplinary team. In the Kidney Disease Outcomes Quality Initiative (KDOQI) classification system of CKD, preparation for renal replacement therapy has been recommended in CKD stage 4, characterized by a reduction in the estimated glomerular filtration rate (GFR) of <30 ml/min. In this article we share our approach to perfecting predialysis care. Tools are given to make an estimation of the progression of kidney disease. Also the prevention and treatment of metabolic complications and cardiovascular risk management are summarized. Finally, the possibilities for dialysis but even more important, aiming for pre-emptive transplantation, are being discussed. Using a multidisciplinary integrated care approach predialysis care has come of age.