Rivaroxaban Plus Aspirin in Patients With Vascular Disease and Renal Dysfunction From the COMPASS Trial

BACKGROUND: Chronic kidney disease is associated with an increased risk of both bleeding and ischemic cardiovascular events.OBJECTIVE: The purpose of this study was to determine the balance of risks and benefits from the dual pathway antithrombotic regimen (rivaroxaban 2.5 mg twice daily [bd] plus aspirin, compared with aspirin) in vascular patients with or without moderate renal dysfunction.METHODS: This was a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial involving 27,395 patients with chronic coronary or peripheral artery disease.RESULTS: In COMPASS, 21,111 patients had an estimated glomerular filtration rate (GFR) at baseline of >= 60 ml/min, 6,276 had a GRF of = 60 ml/min, 3.5% rivaroxaban plus aspirin, 4.5% aspirin alone, hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.64 to 0.90; GFR = 60 ml/min (2.9% rivaroxaban plus aspirin, 1.6% aspirin alone, HR: 1.81; 95% CI: 1.44 to 2.28) and similarly in those with GFR </div

Bone Histomorphometry and 18F‑Sodium Fluoride Positron Emission Tomography Imaging: Comparison Between only Bone Turnover-based and Unified TMV-based Classification of Renal Osteodystrophy

Bone biopsy is the gold standard for characterization of renal osteodystrophy (ROD). However, the classification of the subtypes of ROD based on histomorphometric parameters is not unambiguous and the range of normal values for turnover differ in different publications. F-18-Sodium Fluoride positron emission tomography (F-18-NaF PET) is a dynamic imaging technique that measures turnover. F-18-NaF PET has previously been shown to correlate with histomorphometric parameters. In this cross-sectional study, 26 patients on dialysis underwent a F-18-NaF PET and a bone biopsy. Bone turnover-based classification was assessed using Malluche's historical reference values for normal bone turnover. In unified turnover-mineralization-volume (TMV)-based classification, the whole histopathological picture was evaluated and the range for normal turnover was set accordingly. Fluoride activity was measured in the lumbar spine (L1-L4) and at the anterior iliac crest. On the basis of turnover-based classification of ROD, 12% had high turnover and 61% had low turnover bone disease. On the basis of unified TMV-based classification of ROD, 42% had high turnover/hyperparathyroid bone disease and 23% had low turnover/adynamic bone disease. When using unified TMV-based classification of ROD, F-18-NaF PET had an AUC of 0.86 to discriminate hyperparathyroid bone disease from other types of ROD and an AUC of 0.87, for discriminating adynamic bone disease. There was a disproportion between turnover-based classification and unified TMV-based classification. More research is needed to establish normal range of bone turnover in patients with CKD and to establish the role of PET imaging in ROD

Progression of Aortic Calcification in Stage 4-5 Chronic Kidney Disease Patients Transitioning to Dialysis and Transplantation

Background and Aims: Abdominal aortic calcification (AAC) is common in chronic kidney disease (CKD) patients and associated with increased mortality. Comparative data on the AAC score progression in CKD patients transitioning from conservative treatment to different modalities of renal replacement therapy (RRT) are lacking and were examined. Methods: 150 study patients underwent lateral lumbar radiograph to study AAC in the beginning of the study before commencing RRT (AAC1) and at 3 years of follow-up (AAC2). We examined the associations between repeated laboratory tests taken every 3 months, echocardiographic and clinical variables and AAC increment per year (ΔAAC), and the association between ΔAAC and outcomes during follow-up. Results: At the time of AAC2 measurement, 39 patients were on hemodialysis, 39 on peritoneal dialysis, 39 had a transplant, and 33 were on conservative treatment. Median AAC1 was 4.8 (0.5-9.0) and median AAC2 8.0 (1.5-12.0) (p p = 0.19). ΔAAC was independently associated with mean left ventricular mass index (LVMI) (log LVMI: β = 0.97, p = 0.02) and mean phosphorus through follow-up (log phosphorus: β = 1.19, p = 0.02) in the multivariable model. Time to transplantation was associated with Delta AAC in transplant recipients (per month on the waiting list: β = 0.04, p = 0.001). Delta AAC was associated with mortality (HR 1.427, 95% confidence interval 1.044-1.950, p = 0.03). Conclusion: AAC progresses rapidly in patients with CKD, and ΔAAC is similar across the CKD treatment groups including transplant recipients. The increment rate is associated with mortality and in transplant recipients with the time on the transplant waiting list.</p

Maximal Exercise Capacity in Chronic Kidney Disease Stage 4-5 Patients Transitioning to Renal Replacement Therapy or Continuing Conservative Care: A Longitudinal Follow-Up Study

Introduction: Chronic kidney disease (CKD) is associated with impaired maximal exercise capacity (MEC). However, data are scarce on the development of MEC in CKD stage 4-5 patients transitioning to renal replacement therapy (RRT).Methods: We explored the change in MEC measured in watts (Wlast4) with 2 consecutive maximal bicycle stress ergometry tests in 122 CKD stage 4-5 patients transitioning to dialysis and transplantation in an observational follow-up study.Results: Mean age was 58.9 ± 13.9 years and 43 (35.2%) were female. Mean time between the baseline and follow-up ergometry tests was 1,012 ± 327 days and 29 (23.8%) patients had not initiated RRT, 50 (41.0%) were undergoing dialysis, and 43 (35.2%) had received a kidney transplant at the time of the follow-up ergometry test. The mean Wlast4 was 91 ± 37 W and 84 ± 37 W for the baseline and follow-up ergometry tests, respectively (p Conclusion: MEC declined or remained poor in advanced CKD patients transitioning to RRT or continuing conservative care in this observational study. Mean capillary blood bicarbonate was independently associated with the development of MEC.</p

Dental health assessed using panoramic radiograph and adverse events in chronic kidney disease stage 4-5 patients transitioning to dialysis and transplantation-A prospective cohort study

Background and aimsOral health could potentially be a modifiable risk factor for adverse outcomes in chronic kidney disease (CKD) patients transitioning from predialysis treatment to maintenance dialysis and transplantation. We aimed to study the association between an index of radiographically assessed oral health, Panoramic Tomographic Index (PTI), and cardiovascular and all-cause mortality, major adverse cardiovascular events (MACEs) and episodes of bacteremia and laboratory measurements during a three-year prospective follow-up in CKD stage 4–5 patients not on maintenance dialysis at baseline.MethodsAltogether 190 CKD stage 4–5 patients without maintenance dialysis attended panoramic dental radiographs in the beginning of the study. The patients were followed up for three years or until death. MACEs and episodes of bacteremia were recorded during follow-up. Laboratory sampling for C-reactive protein and leukocytes was repeated tri-monthly.ResultsPTI was not associated with baseline laboratory parameters or C-reactive protein or leukocytes examined as repeated measures through the 3-year follow-up. During follow-up, 22 patients had at least one episode of bacteremia, but only 2 of the bacteremias were considered to be of oral origin. PTI was not associated with incident bacteremia during follow-up. Thirty-six patients died during follow-up including 17 patients due to cardiovascular causes. During follow-up 42 patients were observed with a MACE. PTI was independently associated with all-cause (HR 1.074 95% CI 1.029–1.122, p = 0.001) and cardiovascular (HR 1.105, 95% CI 1.057–1.157, pConclusionsRadiographically assessed dental health is independently associated with all-cause and cardiovascular mortality and MACEs but not with the incidence of bacteremia in CKD stage 4–5 patients transitioning to maintenance dialysis and renal transplantation during follow-up.</p

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial

Background: Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. Methods: This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30–59 mL/min per 1·73 m2, and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete. Findings: Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA1c (estimated mean change of −1·0 percentage point (SE 0·1; −11 mmol/mol [SE 0·8]) vs −0·2 percentage points (SE 0·1; −2 mmol/mol [SE 0·8]); estimated treatment difference [ETD]: −0·8 percentage points, 95% CI −1·0 to −0·6;