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Abstract Background Older patients with advanced chronic kidney disease are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life [HRQoL] and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced chronic kidney disease. Methods An ongoing Dutch multicentre prospective cohort study enrols patients of ≥70 years with an eGFR

Rationale & Objective: Both hypo- and hyperkalemia can cause fatal cardiac arrhythmias. Although predialysis serum potassium level is a known modifiable risk factor for death in patients receiving hemodialysis, especially for hypokalemia, this risk may be underestimated. Therefore, we investigated the relationship between predialysis serum potassium level and death in incident hemodialysis patients and whether there is an optimum level. Study Design: Prospective multicenter cohort study. Setting & Participants: 1,117 incident hemodialysis patients (aged >18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis-2 study were included and followed from their first hemodialysis treatment until death, transplantation, switch to peritoneal dialysis, or a maximum of 10 years. Exposure: Predialysis serum potassium levels were obtained every 6 months and divided into 6 categories: ≤4.0 mmol/L, >4.0 mmol/L to ≤4.5 mmol/L, >4.5 mmol/L to ≤5.0 mmol/L, >5.0 mmol/L to ≤5.5 mmol/L (reference), >5.5 mmol/L to ≤6.0 mmol/L, and >6.0 mmol/L. Outcomes: 6-month all-cause mortality. Analytical Approach: Cox proportional hazards and restricted cubic spline analyses with time-dependent predialysis serum potassium levels were used to calculate the adjusted HRs for death. Results: At baseline, the mean age of the patients was 63 years (standard deviation, 14 years), 58% were men, 26% smoked, 24% had diabetes, 32% had cardiovascular disease, the mean serum potassium level was 5.0 mmol/L (standard deviation, 0.8 mmol/L), 7% had a low subjective global assessment score, and the median residual kidney function was 3.5 mL/min/1.73 m2 (IQR, 1.4-4.8 mL/min/1.73 m2). During the 10-year follow-up, 555 (50%) deaths were observed. Multivariable adjusted HRs for death according to the 6 potassium categories were as follows: 1.42 (95% CI, 1.01-1.99), 1.09 (95% CI, 0.82-1.45), 1.21 (95% CI, 0.94-1.56), 1 (reference), 0.95 (95% CI, 0.71-1.28), and 1.32 (95% CI, 0.97-1.81). Limitations: Shorter intervals between potassium measurements would have allowed for more precise mortality risk estimations. Conclusions: We found a U-shaped relationship between serum potassium level and death in incident hemodialysis patients. A low predialysis serum potassium level was associated with a 1.4-fold stronger risk of death than the optimal level of approximately 5.1 mmol/L. These results may imply the cautious use of potassium-lowering therapy and a potassium-restricted diet in patients receiving hemodialysis.

Objective: Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the ass ociation of subclinical thyroid dysfunction and the risk of cardiovascular outcomes. Methods: In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication us e that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45–4.5 mIU/L); and subclinical hyperthyroidism (TSH 60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke. Results: Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24– 1.07) comparing subclinical hyperthyroidism and 0.90 (0.58–1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism). Conclusions: In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.

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 m 2 ., 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., (© 2024 The Authors.)

Introduction: After decades of increasing dialysis incidence, we observed a decreasing trend in the Netherlands in the last decade. We compared this trend with trends in other European countries., Materials and Methods: Aggregated data for calendar years 2001-2019 from the Dutch registries of kidney replacement therapy patients and the European Renal Association Registry were used. Dialysis incidence in the Netherlands was compared with that in 11 other European countries/regions using three age groups: 20-64, 65-74, and ≥75 years, taking into account pre-emptive kidney transplantation (PKT) incidence. Time trends were assessed as annual percentage change (APC) with 95% confidence intervals (CI) using joinpoint regression analysis., Results: Between 2001 and 2019 the Dutch dialysis incidence decreased slightly among patients aged 20-64 years (APC -0.9, 95% CI -1.4; -0.5). For patients 65-74 and ≥75 years old, a peak was seen in 2004 and 2009, respectively. Afterwards, the decrease was most marked in patients aged ≥75 years: APC -3.2 (-4.1; -2.3) versus APC -1.8 (-2.2; -1.3) for patients 65-74 years old. PKT incidence increased significantly during the study period but remained limited compared to the observed decrease in dialysis incidence, especially among older patients. Large differences in dialysis incidence were observed among European countries/regions. A decreasing dialysis incidence among older patients was also seen in Austria, Denmark, England/Wales, Finland, Scotland, and Sweden., Conclusions: The Dutch dialysis incidence decreased most profoundly among older patients. This was also observed in several other European countries/regions. Although PKT incidence increased, it can only explain a minor part of the decrease in dialysis incidence., Competing Interests: M.O, A.A., M.B., and W.B. are investigators for the DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA) study, which is supported by Leading the Change, a Dutch healthcare efficiency evaluation project by Zorgevaluatie Nederland. K.J. received funding from the European Renal Association (ERA) for running the ERA Registry. W.B. received grant support from Zilveren Kruis Insurance, outside the submitted work. All other authors declare they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Supportive care (SC) is a multidimensional and person-centred approach to managing advanced CKD that engages the person and their caregivers in shared decision making from the outset. Rather than focusing on disease-specific therapies, SC is a collection of adjuvant interventions and adaptations to conventional treatments that can be used to improve the individual's quality of life. Recognizing that frailty, multi-morbidity and polypharmacy are more common among older people with advanced chronic kidney disease (CKD) and that people in this group tend to prioritize quality of life over survival as a goal of care, SC represents an important adjunct to disease-specific therapies in CKD management. This review provides an overview of SC in the older person with advanced CKD., Competing Interests: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Non-dialytic conservative care (CC) has been proposed as a treatment option for patients with kidney failure. This systematic review and meta-analysis aims at comparing survival outcomes between dialysis and CC in studies where patients made an explicit treatment choice., Methods: Five databases were systematically searched from origin through 25 February 2021 for studies comparing survival outcomes among patients choosing dialysis versus CC. Adjusted and unadjusted survival rates were extracted and meta-analysis performed where applicable. Risk of bias analysis was performed according to the Cochrane Risk Of Bias In Non-randomized Studies of Interventions., Results: A total of 22 cohort studies were included covering 21 344 patients. Most studies were prone to selection bias and confounding. Patients opting for dialysis were generally younger and had fewer comorbid conditions, fewer functional impairments and less frailty than patients who chose CC. The unadjusted median survival from treatment decision or an estimated glomerular filtration rate <15 mL/min/1.73 m2 ranged from 20 and 67 months for dialysis and 6 and 31 months for CC. Meta-analysis of 12 studies that provided adjusted hazard ratios (HRs) for mortality showed a pooled adjusted HR of 0.47 (95% confidence interval 0.39-0.57) for patients choosing dialysis compared with CC. In subgroups of patients with older age or severe comorbidities, the reduction of mortality risk remained statistically significant, although analyses were unadjusted., Conclusions: Patients opting for dialysis have an overall lower mortality risk compared with patients opting for CC. However, a high risk of bias and heterogeneous reporting preclude definitive conclusions and results cannot be translated to an individual level., Competing Interests: Outside the submitted work, C.G.N.V. has received grant support from the Dutch Kidney Foundation and Nephrosearch Foundation; W.R.V. has received grant support from Zilveren Kruis; W.J.W.B. has received grant support from Zilveren Kruis and the Dutch Kidney Foundation; and M.v.B has received grant support from the Dutch Kidney Foundation and Healthcare Evaluation Leading the Change. The remaining authors declare that they have no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the ERA.)

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.

Background: Older patients with advanced chronic kidney disease are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life [HRQoL] and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced chronic kidney disease., Methods: An ongoing Dutch multicentre prospective cohort study enrols patients of ≥70 years with an eGFR < 20 mL/min/1.73m 2 from October 2018 onward. With additional questionnaires during the pandemic (May-June 2020), disease-related concerns about COVID-19 and general anxiety symptoms were assessed cross-sectionally, and depressive symptoms, HRQoL, and emotional symptoms longitudinally., Results: The 82 included patients had a median age of 77.5 years (interquartile range 73.9-82.1), 77% were male and none had tested positive for COVID-19. Cross-sectionally, 67% of the patients reported to be more anxious about COVID-19 because of their kidney disease, and 43% of the patients stated that their quality of life was reduced due to the COVID-19 pandemic. Compared to pre-COVID-19, the presence of depressive symptoms had increased (11 to 22%; p = .022) and physical HRQoL declined (M = 40.4, SD = 10.1 to M = 36.1, SD = 10.4; p < .001), particularly in males. Mental HRQoL (M = 50.3, SD = 9.6 to M = 50.4, SD = 9.9; p = .913) and emotional symptoms remained similar., Conclusions: Older patients with advanced chronic kidney disease suffered from disease-related anxiety about COVID-19, increased depressive symptoms and reduced physical HRQoL during the COVID-19 pandemic. The impact of the pandemic on this vulnerable patient group extends beyond increased mortality risk, and awareness of mental wellbeing is important., Trial Registration: The study is registered at the Netherlands Trial Register (NTR), trial number NL7104. Date of registration: 06-06-2018., (© 2021. The Author(s).)

Background: Dialysis withdrawal is a common cause of death in dialysis-dependent patients. This study aims to describe dialysis withdrawal practice in The Netherlands, focussing on time trends, risk factors and centre variation., Methods: Data were retrieved from the Dutch registry of kidney replacement therapy patients. All patients who started maintenance dialysis and died in the period 2000-2019 were included. The main outcome was death after dialysis withdrawal; all other causes of death were used for comparison. Time trends were analysed as unadjusted data (proportion per year) and the year of death was included in a multivariable logistic model. Univariable and multivariable analyses were performed to identify factors associated with withdrawal. Centre variation was compared using funnel plots., Results: A total of 34 692 patients started dialysis and 18 412 patients died while on dialysis. Dialysis withdrawal was an increasingly common cause of death, increasing from 18.3% in 2000-2004 to 26.8% in 2015-2019. Of all patients withdrawing, 26.1% discontinued treatment within their first year. In multivariable analysis, increasing age, female sex, haemodialysis as a treatment modality and year of death were independent factors associated with death after dialysis withdrawal. Centre variation was large (80.7 and 57.4% within 95% control limits of the funnel plots for 2000-2009 and 2010-2019, respectively), even after adjustment for confounding factors., Conclusions: Treatment withdrawal has become the main cause of death among dialysis-dependent patients in The Netherlands, with large variations between centres. These findings emphasize the need for timely advance care planning and improving the shared decision-making process on choosing dialysis or conservative care., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Non-dialytic conservative care (CC) has been proposed as a viable alternative to maintenance dialysis for selected older patients to treat end-stage kidney disease (ESKD). This systematic review compares both treatment pathways on health-related quality of life (HRQoL) and symptoms, which are major outcomes for patients and clinicians when deciding on preferred treatment., Methods: We searched PubMed, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus and PsycINFO from inception to 1 October 2019 for studies comparing patient-reported HRQoL outcomes or symptoms between patients who chose either CC or dialysis for ESKD., Results: Eleven observational cohort studies were identified comprising 1718 patients overall. There were no randomized controlled trials. Studies were susceptible to selection bias and confounding. In most studies, patients who chose CC were older and had more comorbidities and worse functional status than patients who chose dialysis. Results were broadly consistent across studies, despite considerable clinical and methodological heterogeneity. Patient-reported physical health outcomes and symptoms appeared to be worse in patients who chose CC compared with patients who chose dialysis but had not yet started, but similar compared with patients on dialysis. Mental health outcomes were similar between patients who chose CC or dialysis, including before and after dialysis start. In patients who chose dialysis, the burden of kidney disease and impact on daily life increased after dialysis start., Conclusions: The available data, while heterogeneous, suggest that in selected older patients, CC has the potential to achieve similar HRQoL and symptoms compared with a dialysis pathway. High-quality prospective studies are needed to confirm these provisional findings., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background and Objectives: There is concern about potential deleterious effects of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). Patients with kidney failure, who often use ACEis/ARBs, are at higher risk of more severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population., Design, Setting, Participants, & Measurements: From the European Renal Association COVID-19 database (ERACODA), we retrieved data on kidney transplant recipients and patients on dialysis who were affected by COVID-19, between February 1 and October 1, 2020, and had information on 28-day mortality. We used Cox proportional-hazards regression to calculate hazard ratios for the association between ACEi/ARB use and 28-day mortality risk. Additionally, we studied the association of discontinuation of these agents with 28-day mortality., Results: We evaluated 1511 patients: 459 kidney transplant recipients and 1052 patients on dialysis. At diagnosis of COVID-19, 189 (41%) of the transplant recipients and 288 (27%) of the patients on dialysis were on ACEis/ARBs. A total of 88 (19%) transplant recipients and 244 (23%) patients on dialysis died within 28 days of initial presentation. In both groups of patients, there was no association between ACEi/ARB use and 28-day mortality in both crude and adjusted models (in transplant recipients, adjusted hazard ratio, 1.12; 95% confidence interval [95% CI], 0.69 to 1.83; in patients on dialysis, adjusted hazard ratio, 1.04; 95% CI, 0.73 to 1.47). Among transplant recipients, ACEi/ARB discontinuation was associated with a higher mortality risk after adjustment for demographics and comorbidities, but the association was no longer statistically significant after adjustment for severity of COVID-19 (adjusted hazard ratio, 1.36; 95% CI, 0.40 to 4.58). Among patients on dialysis, ACEi/ARB discontinuation was not associated with mortality in any model. We obtained similar results across subgroups when ACEis and ARBs were studied separately, and when other outcomes for severity of COVID-19 were studied, e.g. , hospital admission, admission to the intensive care unit, or need for ventilator support., Conclusions: Among kidney transplant recipients and patients on dialysis with COVID-19, there was no significant association of ACEi/ARB use or discontinuation with mortality., (Copyright © 2021 by the American Society of Nephrology.)

Background: The incidence and prevalence of older patients with kidney failure who are dependent on dialysis is increasing. However, observational studies showed limited or no benefit of dialysis on mortality in subgroups of these patients when compared to conservative care. As the focus is shifting towards health-related quality of life (HRQoL), current evidence of effects of conservative care or dialysis on HRQoL in older patients is both limited and biased. Dialysis comes with both high treatment burden for patients and high costs for society; better identification of patients who might not benefit from dialysis could result in significant cost savings. The aim of this prospective study is to compare HRQoL, clinical outcomes, and costs between conservative care and dialysis in older patients., Methods: The DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA) study is a prospective, observational cohort study that started in February 2020. It aims to include 1500 patients from 25 Dutch and Belgian centres. Patients aged ≥70 years with an eGFR of 10-15 mL/min/1.73m 2 are enrolled in the first stage of the study. When dialysis is initiated or eGFR drops to 10 mL/min/1.73m 2 or lower, the second stage of the study commences. In both stages nephrogeriatric assessments will be performed annually, consisting of questionnaires and tests to assess most common geriatric domains, i.e. functional, psychological, somatic, and social status. The primary outcome is HRQoL, measured with the Twelve-item Short-Form Health Survey. Secondary outcomes are clinical outcomes (mortality, hospitalisation, functional status, cognitive functioning, frailty), cost-effectiveness, and decisional regret. All outcomes are (repeated) measures during the first year of the second stage. The total follow-up will be a maximum of 4 years with a minimum of 1 year in the second stage., Discussion: By generating more insight in the effects of conservative care and dialysis on HRQoL, clinical outcomes, and costs, findings of this study will help patients and physicians make a shared decision on the best individual treatment option for kidney failure., Trial Registration: The study was registered in the Netherlands Trial Register ( NL-8352 ) on 5 February 2020.

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.

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 m 2 ) 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.

Background: Conservative care (CC) may be a valid alternative to dialysis for certain older patients with advanced chronic kidney disease (CKD). A model that predicts patient prognosis on both treatment pathways could be of value in shared decision-making. Therefore, the aim is to develop a prediction tool that predicts the mortality risk for the same patient for both dialysis and CC from the time of treatment decision., Methods: CKD Stage 4/5 patients aged ≥70 years, treated at a single centre in the Netherlands, were included between 2004 and 2016. Predictors were collected at treatment decision and selected based on literature and an expert panel. Outcome was 2-year mortality. Basic and extended logistic regression models were developed for both the dialysis and CC groups. These models were internally validated with bootstrapping. Model performance was assessed with discrimination and calibration., Results: In total, 366 patients were included, of which 126 chose CC. Pre-selected predictors for the basic model were age, estimated glomerular filtration rate, malignancy and cardiovascular disease. Discrimination was moderate, with optimism-corrected C-statistics ranging from 0.675 to 0.750. Calibration plots showed good calibration., Conclusions: A prediction tool that predicts 2-year mortality was developed to provide older advanced CKD patients with individualized prognosis estimates for both dialysis and CC. Future studies are needed to test whether our findings hold in other CKD populations. Following external validation, this prediction tool could be used to compare a patient's prognosis on both dialysis and CC, and help to inform treatment decision-making., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Chronic kidney disease (CKD) has been identified as a significant direct marker for cognitive decline, but controversy exists regarding the magnitude of the association of kidney function with cognitive decline across the different CKD stages. Therefore, the aim of this study was to investigate the association of kidney function with cognitive decline in older patients at high risk of cardiovascular disease, using data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)., Methods: Data of 5796 patients of PROSPER were used. Strata were made according to clinical stages of CKD based on estimated glomerular filtration rate; < 30 ml/min/1.73m 2 (stage 4), 30-45 ml/min/1.73m 2 (stage 3b), 45-60 ml/min/1.73m 2 (stage 3a) and ≥ 60 ml/min/1.73m 2 (stage 1-2). Cognitive function and functional status was assessed at six different time points and means were compared at baseline and over time, adjusted for multiple prespecified variables. Stratified analyses for history of vascular disease were executed., Results: Mean age was 75.3 years and 48.3% participants were male. Mean follow-up was 3.2 years. For all cognitive function tests CKD stage 4 compared to the other stages had the worst outcome at baseline and a trend for faster cognitive decline over time. When comparing stage 4 versus stage 1-2 over time the estimates (95% CI) were 2.23 (0.60-3.85; p = 0.009) for the Stroop-Colour-Word test, - 0.33 (- 0.66-0.001; p = 0.051) for the Letter-Digit-Coding test, 0.08 (- 0.06-0.21; p = 0.275) for the Picture-Word-Learning test with immediate recall and - 0.07 (- 0.02-0.05; p = 0.509) for delayed recall. This association was most present in patients with a history of vascular disease. No differences were found in functional status., Conclusion: In older people with vascular burden, only severe kidney disease (CKD stage 4), but not mild to modest kidney disease (CKD stage 3a and b), seem to be associated with cognitive impairment at baseline and cognitive decline over time. The association of severe kidney failure with cognitive impairment and decline over time was more outspoken in patients with a history of vascular disease, possibly due to a higher probability of polyvascular damage, in both kidney and brain, in patients with proven cardiovascular disease.

The Dutch prospective multicenter cohort study COPE (Cognitive decline in Older Patients with End stage renal disease) aimed to investigate the association of cardiovascular structure and function with cerebrovascular changes and cognitive function in 85 older patients with chronic kidney disease stage 4 and 5, awaiting either dialysis or conservative care. MRI was performed measuring aortic stiffness (pulse wave velocity [PWV]) and cardiac systolic function (ejection fraction and cardiac index). Outcomes were MRI-derived cerebrovascular changes (microbleeds, lacunes and white matter hyperintensities) and cognitive function (memory, executive function and psychomotor speed). Mean age was 76 years and 66% were male. No statistically significant associations were observed between cardiovascular parameters and cerebrovascular changes. Cognitive function was worse in patients with high compared to low PWV in all three cognitive domains. Although there were clinically relevant associations of high PWV with poor cognition in all domains, after adjustment for age, sex and education only the Trail Making Test A remained statistically significant (p=0.030). In conclusion, this study suggests that a higher PWV might be associated with lower cognitive function, suggesting that arterial stiffness may be an underlying mechanism of development of cognitive impairment in older patients with ESRD. Larger studies should replicate and extend these findings.

Objective: Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes., Methods: In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45-4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45-60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke., Results: Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24-1.07) comparing subclinical hyperthyroidism and 0.90 (0.58-1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism)., Conclusions: In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.

Background: Vancomycin is frequently used in hemodialysis (HD) and in hemodiafiltration (HDF) patients and is usually administered in the last 30 or 60 minutes of a dialysis session. Vancomycin pharmacokinetics are not well described in HDF patients. The aim of this study is to develop a population pharmacokinetic (PPK) model and dosing regimen for vancomycin in HDF patients and to evaluate its applicability in low-flux (LF-HD) patients., Methods: Two-compartment PPK models were developed using data from HDF patients (n = 17), and was parameterized as follows: non-renal clearance (CLm), renal clearance as a fraction of creatinine clearance (fr), central volume of distribution (V1), intercompartmental clearance (CL12), peripheral volume of distribution (V2) and extracorporeal extraction ratio (Eec). We evaluated the final model in a cohort of LF-HD patients (n = 21). Dosing schemes were developed for a vancomycin 24-h AUC of 400 mg*h/L., Results: Model parameters (± SD) were: CLm = 0.473 (0.271) L/h, fr = 0.1 (fixed value), V1 = 0.278 (0.092) L/kgLBMc, CL12 = 9.96 L/h (fixed value), V2 = 0.686 (0.335) L/kgLBMc and Eec = 0.212 (0.069). The model reliably predicted serum levels of vancomycin in both HDF and LF-HD patients during and between dialysis sessions. The median of the prediction error (MDPE) as a measure of bias is -0.7% (95% CI: -3.4%-1.7%) and the median of the absolute values of the prediction errors (MDAPE) as a measure of precision is 7.9% (95% CI: 6.0%-9.8%). In both HDF and LF-HD, the optimal vancomycin loading dose for a typical patient weighing 70 kg is 1700 mg when administered during the last 60 minutes of the hemodialysis session. Maintenance dose is 700 mg if administered during the last 30 or 60 minutes of the hemodialysis session., Conclusion: The developed PPK model for HDF is also capable of predicting serum levels of vancomycin in patients on LF-HD. A dosing regimen was developed for the use of vancomycin in HDF and LF-HD., Competing Interests: The authors have declared that no competing interests exist.