The association of kidney function and cognitive decline in older patients at risk of cardiovascular disease: a longitudinal data analysis

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/1.73m2 (stage 4), 30-45 ml/min/1.73m2 (stage 3b), 45-60 ml/min/1.73m2 (stage 3a) and ≥ 60 ml/min/1.73m2 (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

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

Health-related quality of life and symptom burden in patients on haemodialysis

BACKGROUND: Patients on haemodialysis generally experience poor health-related quality of life (HRQoL) and a broad range of physical and mental symptoms, but it is unknown whether this differs between younger and older patients. We aimed to describe the trajectories of HRQoL and symptom burden of patients &lt; 70 and ≥ 70 years old, and to assess the impact of symptom burden on HRQoL.METHODS: In incident Dutch haemodialysis patients, HRQoL and symptoms were measured with the 12-item Short Form Health Survey and Dialysis Symptom Index. We used linear mixed models for examining the trajectories of HRQoL and symptom burden during the first year of dialysis, and linear regression for the impact of symptom burden on HRQoL.RESULTS: In 774 patients, the trajectories of physical HRQoL, mental HRQoL, and symptom burden were stable during the first year of dialysis. Compared with patients aged &lt; 70 years, patients ≥ 70 years reported similar physical HRQoL (mean difference -0.61, 95% CI -1.86; 0.63), better mental HRQoL (1.77, 95% CI 0.54; 3.01), and lower symptom burden (-2.38, 95% CI -5.08; 0.32). With increasing symptom burden, physical HRQoL declined more in older than in younger patients (β -0.287 versus -0.189, respectively, p-value for interaction = 0.007). For mental HRQoL, this decrease was similar in both age groups (β -0.295 versus -0.288, P = 0.847).CONCLUSIONS: Older haemodialysis patients generally experience a better mental HRQoL and a (non-statistically significant) lower symptom burden, compared to younger patients. Their physical HRQoL declines more rapidly with increasing symptom burden.</p

Barriers to and Facilitators of Sustained Employment:A Qualitative Study of Experiences in Dutch Patients With CKD

Rationale & Objective: Although patients with chronic kidney disease (CKD) are at risk for work disability and loss of employment, not all experience work disruption. We aimed to describe the barriers to and facilitators of sustained employment experienced by Dutch patients with CKD. Study Design: Qualitative study using semi-structured interviews. Setting & Participants: 27 patients with CKD glomerular filtration rate categories 3b-5 (G3b-G5) from 4 nephrology outpatient clinics in The Netherlands. Analytical Approach: Content analyses with constant comparison of interview data based on the International Classification of Functioning, Disability and Health framework. Results: Participants were 6 patients with CKD G3b-G4, 8 patients receiving maintenance dialysis, and 13 patients with functioning kidney transplants. We identified health-related barriers (symptoms, physical toll of dialysis/transplantation, limited work capacity) and facilitators (few physical symptoms, successful posttransplantation recovery, absence of comorbidities, good physical condition), personal barriers (psychological impact, limited work experience) and facilitators (positive disposition, job satisfaction, work attitude, person-job fit), and environmental barriers and facilitators. Environmental barriers were related to nephrology care (waiting time, use of a hemodialysis catheter) and work context (reorganization, temporary contract, working hours, physical demands); environmental facilitators were related to nephrology care (personalized dialysis, preemptive transplant), work context (large employer, social climate, job requiring mental rather than physical labor, flexible working hours, adjustment of work tasks, reduced hours, remote working, support at work, peritoneal dialysis exchange facility), and support at home. Occupational health services and social security could be barriers or facilitators. Limitations: The study sample of Dutch patients may limit the transferability of these findings to other countries. Conclusions: The wide range of barriers and facilitators in all International Classification of Functioning, Disability and Health components suggests great diversity among patients and their circumstances. These findings underline the importance of personalized nephrology and occupational health care as well as the importance of individually tailored workplace accommodations to promote sustained employment for patients with CKD

Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kidney Injury in Adults With Chronic Kidney Disease The Kompas Randomized Clinical Trial

Importance Prevention of postcontrast acute kidney injury in patients with stage 3 chronic kidney disease (CKD) by means of prehydration has been standard care for years. However, evidence for the need for prehydration in this group is limited. Objective To assess the renal safety of omitting prophylactic prehydration prior to iodine-based contrast media administration in patients with stage 3 CKD. Design, Setting, and Participants The Kompas trial was a multicenter, noninferiority, randomized clinical trial conducted at 6 hospitals in the Netherlands in which 523 patients with stage 3 CKD were randomized in a 1:1 ratio to receive no prehydration or prehydration with 250 mL of 1.4% sodium bicarbonate administered in a 1-hour infusion before undergoing elective contrast-enhanced computed tomography from April 2013 through September 2016. Final follow-up was completed in September 2017. Data were analyzed from January 2018 to June 2019. Interventions In total, 262 patients were allocated to the no prehydration group and 261 were allocated to receive prehydration. Analysis on the primary end point was available in 505 patients (96.6%). Main Outcomes and Measures The primary end point was the mean relative increase in serum creatinine level 2 to 5 days after contrast administration compared with baseline (noninferiority margin of less than 10% increase in serum creatinine level). Secondary outcomes included the incidence of postcontrast acute kidney injury 2 to 5 days after contrast administration, mean relative increase in creatinine level 7 to 14 days after contrast administration, incidences of acute heart failure and renal failure requiring dialysis, and health care costs. Results Of 554 patients randomized, 523 were included in the intention-to-treat analysis. The median (interquartile range) age was 74 (67-79) years; 336 (64.2%) were men and 187 (35.8%) were women. The mean (SD) relative increase in creatinine level 2 to 5 days after contrast administration compared with baseline was 3.0% (10.5) in the no prehydration group vs 3.5% (10.3) in the prehydration group (mean difference, 0.5; 95% CI, -1.3 to 2.3; P <.001 for noninferiority). Postcontrast acute kidney injury occurred in 11 patients (2.1%), including 7 of 262 (2.7%) in the no prehydration group and 4 of 261 (1.5%) in the prehydration group, which resulted in a relative risk of 1.7 (95% CI, 0.5-5.9; P = .36). None of the patients required dialysis or developed acute heart failure. Subgroup analyses showed no evidence of statistical interactions between treatment arms and predefined subgroups. Mean hydration costs were euro119 (US $143.94) per patient in the prehydration group compared with euro0 (US$0) in the no prehydration group (P <.001). Other health care costs were similar. Conclusions and Relevance Among patients with stage 3 CKD undergoing contrast-enhanced computed tomography, withholding prehydration did not compromise patient safety. The findings of this study support the option of not giving prehydration as a safe and cost-efficient measure

Multifactorial approach and superior treatment efficacy in renal patients with the aid of nurse practitioners. Design of The MASTERPLAN Study [ISRCTN73187232]

BACKGROUND: Patients with chronic kidney disease (CKD) are at a greatly increased risk of developing cardiovascular disease. Recently developed guidelines address multiple risk factors and life-style interventions. However, in current practice few patients reach their targets. A multifactorial approach with the aid of nurse practitioners was effective in achieving treatment goals and reducing vascular events in patients with diabetes mellitus and in patients with heart failure. We propose that this also holds for the CKD population. DESIGN: MASTERPLAN is a multicenter randomized controlled clinical trial designed to evaluate whether a multifactorial approach with the aid of nurse-practicioners reduces cardiovascular risk in patients with CKD. Approximately 800 patients with a creatinine clearance (estimated by Cockcroft-Gault) between 20 to 70 ml/min, will be included. To all patients the same set of guidelines will be applied and specific cardioprotective medication will be prescribed. In the intervention group the nurse practitioner will provide lifestyle advice and actively address treatment goals. Follow-up will be five years. Primary endpoint is the composite of myocardial infarction, stroke and cardiovascular mortality. Secondary endpoints are cardiovascular morbidity, overall mortality, decline of renal function, change in markers of vascular damage and change in quality of life. Enrollment has started in April 2004 and the study is on track with 700 patients included on October 15th, 2005. This article describes the design of the MASTERPLAN study

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (&gt;= 65 years; estimated glomerular filtration rate &lt;= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off &lt;= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Vancomycin pharmacokinetic model development in patients on intermittent online hemodiafiltration

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

Renin-Angiotensin System Blockers and the Risk of COVID-19-Related Mortality in Patients with Kidney Failure

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