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Background Although cardiovascular morbidity and mortality are substantial in patients with chronic kidney disease (CKD), guideline-directed treatment of cardiovascular risk factors remains a challenge. Methods Observational, cross-sectional study including patients aged 30–75 years with CKD stage 1–5 without kidney replacement therapy from a tertiary hospital outpatient clinic. Data were obtained through patient interview, clinical examination, biochemical work-up, and evaluation of medical records and prescription redemptions. Guideline-directed treatment was evaluated as pharmacological interventions: antihypertensive and lipid-lowering therapy including adverse effects and adherence estimated as medication possession ratio (MPR); and non-pharmacological interventions: smoking status, alcohol consumption, body mass index (BMI), and physical activity. Results The cohort comprised 741 patients, mean age 58 years, 61.4% male, 50.6% CKD stage 3, 61.0% office blood pressure ≤140/90 mmHg. Antihypertensives were prescribed to 87.0%, median number of medications 2 (IQR 1;3), 70.1% received renin–angiotensin system inhibition, 25.9% reported adverse effects. Non-adherence (MPR < 80%) was present in 23.4% and associated with elevated blood pressure (OR 1.53 (95% CI 1.03;2.27)) and increased urinary albumin excretion, P < 0.001. Lipid-lowering treatment was prescribed to 54.0% of eligible patients, 11.1% reported adverse effects, and 28.5% were non-adherent, which was associated with higher LDL cholesterol, P = 0.036. Overall, 19.2% were current smokers, 16.7% overconsumed alcohol according to Danish health authority recommendations 69.3% had BMI ≥ 25 kg/m2, and 38.3% were physically active <4 hours/week. Among patients prescribed antihypertensives, 51.9% reported having received advice on non-pharmacological interventions. Conclusions Improved management of cardiovascular risk in patients with CKD entails intensified medical treatment and increased focus on patient adherence and non-pharmacological interventions. Graphical Abstract Graphical Abstract

Background Patients with chronic kidney disease (CKD) and arterial calcification are considered at increased risk of adverse cardiovascular outcomes. However, the optimal site for measurement of arterial calcification has not been determined. The primary aim of this study was to examine the pattern of arterial calcification in different stages of CKD. Methods This was an observational, cross-sectional study that included 580 individuals with CKD stages 1–5 (no dialysis) from the Copenhagen CKD Cohort. Calcification of the carotid, coronary and iliac arteries, thoracic and abdominal aorta was assessed using non-contrast multidetector computed tomography scans and quantified according to the Agatston method. Based on the distribution of Agatston scores in the selected arterial region, the subjects were divided into calcium score categories of 0 (no calcification), 1–100, 101–400 and > 400. Results Participants with CKD stages 3–5 had the highest prevalence of calcification and the highest frequency of calcium scores > 400 in all arterial sites. Calcification in at least one arterial site was present in > 90% of patients with CKD stage 3. In all five CKD stages prevalence of calcification was greatest in both the thoracic and abdominal aorta, and in the iliac arteries. These arterial sites also showed the highest calcium scores. High calcium scores (> 400) in all five arterial regions were independently associated with prevalent cardiovascular disease. In multivariable analyses, after adjusting for cardiovascular risk factors, declining creatinine clearance was associated with increasing calcification of the coronary arteries ( p  = 0.012) and the thoracic aorta ( p  = 0.037) only. Conclusions Arterial calcification is highly prevalent throughout all five CKD stages and is most prominent in both the thoracic and abdominal aorta, and in the iliac arteries. Follow-up studies are needed to explore the potential of extracardiac calcification sites in prediction of cardiovascular events in the CKD population.

BackgroundMyocardial work is a novel echocardiographic measure that offers detailed insights into cardiac mechanics. We sought to characterize cardiac function by myocardial work in patients with chronic kidney disease (CKD).MethodsWe prospectively enrolled 757 patients with non-dialysis-dependent CKD and 174 age- and sex-matched controls. Echocardiographic pressure-strain loop analysis was performed to acquire the global work index (GWI). Linear regressions were performed to investigate the association between estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) to GWI.ResultsPatients with CKD had a mean age of 57 years, 61% were men, and median eGFR was 42 mL/min/1.73 m2. Overall, no difference in GWI was observed between patients and controls (1879 vs. 1943 mmHg%, p = 0.06). However, a stepwise decline in GWI was observed for controls vs. patients with CKD without left ventricular hypertrophy vs. patients with CKD and left ventricular hypertrophy (GWI, 1943 vs. 1887 vs. 1789 mmHg%; p for trend = 0.030). In patients with CKD, eGFR was not associated with GWI by linear regression. However, diabetes modified this association (p for interaction = 0.007), such that per 10 mL/min/1.73 m2 decrease in eGFR, GWI decreased by 22 (9–35) mmHg% (p = 0.001) after multivariable adjustments in patients without diabetes, but with no association between eGFR and GWI in patients with diabetes. No association was observed between UACR and GWI.ConclusionPatients with CKD and left ventricular hypertrophy exhibited lower myocardial work compared to matched controls. Furthermore, decreasing eGFR was associated with decreasing myocardial work only in patients without diabetes. No association to UACR was observed.

PurposeWe investigated the associations between cardiac parameters and aetiologies of CKD in an exploratory study.MethodsThe study population consisted of 883 participants, 174 controls and 709 patients with aetiologies of CKD including diabetic nephropathy/renovascular KD in diabetes mellitus, hypertensive/renovascular nephropathy, tubulointerstitial nephritis, glomerulonephritis/vasculitis, polycystic KD (PKD), and CKD of unknown origin. Echocardiographic measures included left ventricular (LV) ejection fraction, global longitudinal, area, and radial strain, E/e’ ratio, and LV mass index. These were compared between each aetiological group and controls in unadjusted and adjusted analysis.ResultsIn unadjusted analysis, patients with diabetic nephropathy/renovascular KD in diabetes mellitus, had impaired LV ejection fraction (Median [IQR]: 56% [49.9,60.69] vs. 60.8% [57.7,64.1]), global longitudinal (mean ± SD: 13.1 ± 3.5% vs. 15.5 ± 2.6%), area (24.1 ± 5.8% vs. 28.5 ± 4.2%), and radial strain (36.2 ± 11.2% vs. 44.1 ± 9.7%), and increased LV mass index (89.1 g/m2 [71.8,104.9] vs. 69,0 g/m2 [57.9,80.8]) and E/e’ ratio (10.6 [8.5,12.6] vs. 7 [5.8,8.3], p < 0.001 for all) compared with controls. Associations were similar for CKD of unknown origin. Patients with hypertensive/renovascular nephropathy had impaired global longitudinal and area strain, and higher E/e’ ratio. Patients with glomerulonephritis/vasculitis had higher LV mass index, while patients with PKD had better global longitudinal strain than controls. All findings remained significant in adjusted analysis, except for the impaired global longitudinal strain in hypertensive/renovascular nephropathy.ConclusionGlomerulonephritis/vasculitis, hypertensive/renovascular nephropathy, CKD of unknown origin, and diabetic nephropathy/renovascular KD in diabetes mellitus were increasingly associated with adverse cardiac findings, while PKD and tubulointerstitial nephritis were not. Aetiology might play a role regarding the cardiac manifestations of CKD.A graphical summary of the study population and main results. Abbreviations: DN = Diabetic nephropathy and renovascular kidney disease in diabetes mellitus, PKD = Polycystic kidney disease, CKDu = Chronic kidney disease of unknown origin, LVEF = Left ventricular ejection fraction, LVMi = Left ventricular mass index, E/e’ ratio = Early mitral inflow velocity to mitral annular early diastolic velocity ratio, GLS = Global longitudinal strain, GAS = Global area strain, GRS = Global radial strain.

Cardiovascular disease is the leading cause of mortality amongst patients with chronic kidney disease (CKD). This is the first study using 3-dimensional echocardiography (3DE) to investigate associations between adverse changes of the left ventricle, and different stages of CKD. Participants were recruited from the Copenhagen CKD cohort study and the Herlev-Gentofte CKD cohort study. Patients were stratified according to GFR category (G1 + 2: eGFR ≥ 60 mL/min/1.73 m2, G3: eGFR = 30–59 mL/min/1.73 m2, and G4 + 5: eGFR ≤ 29 mL/min/1.73 m2), and according to albuminuria (A1: UACR < 30 mg/g, A2: 30–300 mg/g, A3: > 300 mg/g). Echocardiograms were analysed for left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), and global strain measures. In adjusted analysis, eGFR groups were adjusted for confounders and albuminuria category, while albuminuria groups were adjusted for confounders and GFR category. The study population consisted of 662 outpatients with CKD and 169 controls. Mean age was 57 ± 13 years, and 61% were males. Mean LVEF and global longitudinal strain (GLS) were increasingly impaired across eGFR groups: LVEF = 60.1%, 58.4%, and 57.8% (p = 0.013), GLS =  − 16.1%, − 14.8%, and − 14.6% (p < 0.0001) for G1 + 2, G3, and G4 + 5. LVMi and prevalence of LV hypertrophy increased with albuminuria severity: mean LVMi = 87.9 g/m2, 88.1 g/m2, and 92.1 g/m2 (p = 0.007) from A1-3. Adjusted analysis confirmed reduced LVEF in G3 compared with G1 + 2, and increased LVMi in A3 compared with A1. Increasingly impaired eGFR was associated with adverse changes in LV systolic function, while albuminuria was associated with adverse changes in LV mass assessed by 3DE. Their associations were independent of each other.

IntroductionAtrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit.Methods and analysisThe DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0–3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient.Ethics and disseminationThe study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals.Trial registration numbersNCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.