The impact of different GFR estimating equations on the prevalence of CKD and risk groups in a Southeast Asian cohort using the new KDIGO guidelines

<p>Abstract</p> <p>Background</p> <p>Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group recommended that patients with CKD should be assigned to stages and composite relative risk groups according to GFR (G) and proteinuria (A) criteria. Asians have among the highest rates of ESRD in the world, but establishing the prevalence and prognosis CKD is a problem for Asian populations since there is no consensus on the best GFR estimating (eGFR) equation. We studied the effects of the choice of new Asian and Caucasian eGFR equations on CKD prevalence, stage distribution, and risk categorization using the new KDIGO classification.</p> <p>Methods</p> <p>The prevalence of CKD and composite relative risk groups defined by eGFR from with Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI); standard (S) or Chinese(C) MDRD; Japanese CKD-EPI (J-EPI), Thai GFR (T-GFR) equations were compared in a Thai cohort (n = 5526)</p> <p>Results</p> <p>There was a 7 fold difference in CKD_3-5prevalence between J-EPI and the other Asian eGFR formulae. CKD_3-5prevalence with S-MDRD and CKD-EPI were 2 - 3 folds higher than T-GFR or C-MDRD. The concordance with CKD-EPI to diagnose CKD_3-5was over 90% for T-GFR or C-MDRD, but they only assigned the same CKD stage in 50% of the time. The choice of equation also caused large variations in each composite risk groups especially those with mildly increased risks. Different equations can lead to a reversal of male: female ratios. The variability of different equations is most apparent in older subjects. Stage G3aA1 increased with age and accounted for a large proportion of the differences in CKD_3-5between CKD-EPI, S-MDRD and C-MDRD.</p> <p>Conclusions</p> <p>CKD prevalence, sex ratios, and KDIGO composite risk groupings varied widely depending on the equation used. More studies are needed to define the best equation for Asian populations.</p

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The metabolic syndrome and chronic kidney disease in a Southeast Asian cohort

US adults with metabolic syndrome, as defined by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, have been shown to be at increased risk of chronic kidney disease (CKD), but there is limited information in other populations. The relationship between metabolic syndrome and CKD (defined as estimated glomerular filtration rate <60ml/min/1.73m2) was examined in a Southeast Asian cohort. This relationship was examined when the subjects (n=3195) were initially recruited in a cross-sectional analysis. The risks of developing new CKD associated with metabolic syndrome were also examined prospectively in a subgroup (n=2067) without CKD at entry after 12 years follow-up. Metabolic syndrome was defined according to both NCEP ATP III and the new International Diabetes Federation (IDF) criteria. The prevalence of CKD was 1.6%, and the incidence of new CKD was 6.3%. Metabolic syndrome by NCEP ATP III definition was associated with the increased risk of CKD at baseline (adjusted odds ratio (OR) 2.48 and 95% confidence interval 1.33–4.62), and of developing new CKD at follow-up (adjusted OR 1.62 and 95% confidence interval 1.00–2.61). There was a significant graded relationship between the number of metabolic syndrome components present and risk of CKD. By contrast, metabolic syndrome by IDF definition was not associated with increased risk of CKD. These results suggest the relationship between CKD and metabolic syndrome in a Southeast Asian population is highly dependent on the criteria used to define metabolic syndrome

Prognostic effect of mean platelet volume in patients with coronary artery disease: A systematic review and meta-analysis

Large platelets with high haemostatic activity may lead to increased platelet aggregation.. Mean platelet volume (MPV), an indicator of platelet reactivity, may emerge as a prognostic marker in patients with coronary artery disease (CAD). It was the objective of this study to conduct a systematic review and meta-analysis to assess prognostic effects of MPV on cardiovascular events (CVE) in CAD patients. We searched MEDLINE and SCOPUS from inception to January 2, 2014. All studies that reported MPV and the incidence of cardiovascular events in CAD patients were included. Two reviewers independently extracted the data. A random-effects model was applied for pooling the mean difference of MPV between patients with vs without CVE. Among 30 eligible studies, eight studies reported mean difference of MPV between CVE groups, 11 studies reported MPV dichotomous into high vs low MPV groups, and 11 studies reported both. The pooled mean difference was 0.69 fL (95 %CI = 0.36, 1.01), i. e. patients with CVE had a MPV about 0.69 fL higher than non-CVE. Patients with higher MPV were about 12 % more likely to die than patients with lower MPV (RR 1.12; 95 %CI = 1.02-1.24). However, pooling these effects was based on high heterogeneity and the source of heterogeneity could not be identified. This might be explained by many differences among included studies (e. g. study population, outcomes of interest, analysate, time between blood collection and MPV analysis, etc). These findings suggest that MPV may be a useful prognostic marker in patients with CAD