Bioimpedance in CKD: an untapped resource?

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Predictors of atherosclerotic events in patients on haemodialysis: post hoc analyses from the AURORA Study

Background: Patients on haemodialysis (HD) are at high risk for cardiovascular events, but heart failure and sudden death are more common than atherosclerotic events. The A Study to Evaluate the Use of Rosuvastatinin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events (AURORA) trial was designed to assess the effect of rosuvastatin on myocardial infarction and death from any cardiac cause in 2773 HD patients. We studied predictors of the atherosclerotic cardiovascular events in AURORA. Methods: We readjudicated all deaths and presumed myocardial infarctions according to the criteria used in the Study of Heart and Renal Protection (SHARP); these were specifically developed to separate atherosclerotic from non-atherosclerotic cardiovascular events. The readjudicated atherosclerotic end point included the first event of the following: non-fatal myocardial infarction, fatal coronary heart disease, non-fatal and fatal non-haemorrhagic stroke, coronary revascularization procedures and death from ischaemic limb disease. Stepwise Cox regression analysis was used to identify the predictors of such events. Results: During a mean follow-up of 3.2 years, 506 patients experienced the new composite atherosclerotic outcome. Age, male sex, prevalent diabetes, prior cardiovascular disease, weekly dialysis duration, baseline albumin [hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.94–0.99 per g/L increase], high-sensitivity C-reactive protein (HR 1.13; 95% CI 1.04–1.22 per mg/L increase) and oxidized low-density lipoprotein (LDL) cholesterol (HR 1.09; 95% CI 1.03–1.17 per 10 U/L increase) were selected as significant predictors in the model. Neither LDL cholesterol nor allocation to placebo/rosuvastatin therapy predicted the outcome. Conclusions: Even with the use of strict criteria for end point definition, non-traditional risk factors, but not lipid disturbances, predicted atherosclerotic events in HD patients

Conventional and Genetic Evidence on the Association between Adiposity and CKD

Background The size of any causal contribution of central and general adiposity to CKD risk and the underlying mechanism of mediation are unknown. Methods Data from 281,228 UK Biobank participants were used to estimate the relevance of waist-to-hip ratio and body mass index (BMI) to CKD prevalence. Conventional approaches used logistic regression. Genetic analyses used Mendelian randomization (MR) and data from 394 waist-to-hip ratio and 773 BMI-associated loci. Models assessed the role of known mediators (diabetes mellitus and BP) by adjusting for measured values (conventional analyses) or genetic associations of the selected loci (multivariable MR). Results Evidence of CKD was found in 18,034 (6.4%) participants. Each 0.06 higher measured waist-to-hip ratio and each 5-kg/m2 increase in BMI were associated with 69% (odds ratio, 1.69; 95% CI, 1.64 to 1.74) and 58% (1.58; 1.55 to 1.62) higher odds of CKD, respectively. In analogous MR analyses, each 0.06–genetically-predicted higher waist-to-hip ratio was associated with a 29% (1.29; 1.20 to 1.38) increased odds of CKD, and each 5-kg/m2 genetically-predicted higher BMI was associated with a 49% (1.49; 1.39 to 1.59) increased odds. After adjusting for diabetes and measured BP, chi-squared values for associations for waist-to-hip ratio and BMI fell by 56%. In contrast, mediator adjustment using multivariable MR found 83% and 69% reductions in chi-squared values for genetically-predicted waist-to-hip ratio and BMI models, respectively. Conclusions Genetic analyses suggest that conventional associations between central and general adiposity with CKD are largely causal. However, conventional approaches underestimate mediating roles of diabetes, BP, and their correlates. Genetic approaches suggest these mediators explain most of adiposity-CKD–associated risk.</p

Cardiovascular outcomes reported in hemodialysis trials

Patients on long-term hemodialysis are at very high risk for cardiovascular disease but are usually excluded from clinical trials conducted in the general population or in at-risk populations. There are no universally agreed cardiovascular outcomes for trials conducted specifically in the hemodialysis population. In this review, we highlight that trials reporting cardiovascular outcomes in hemodialysis patients are usually of short duration (median 3 to 6 months) and are small (59% of trials have \u3c100 participants). Overall, the cardiovascular outcomes are very heterogeneous and may not reflect outcomes that are meaningful to patients and clinicians in supporting decision making, as they are often surrogates of uncertain clinical importance. Composite outcomes used in different trials rarely share the same components. In a field in which a single trial is often insufficiently powered to fully assess the clinical and economic impact of interventions, differences in outcome reporting across trials make the task of meta-analysis and interpretation of all the available evidence challenging. Core outcome sets are now being established across many specialties in health care to prevent these problems. Through the global Standardized Outcomes in Nephrology-Hemodialysis initiative, cardiovascular disease was identified as a critically important core domain to be reported in all trials in hemodialysis. Informed by the current state of reporting of cardiovascular outcomes, a core outcome measure for cardiovascular disease is currently being established with involvement of patients, caregivers, and health professionals. Consistent reporting of cardiovascular outcomes that are critically important to hemodialysis patients and clinicians will strengthen the evidence base to inform care in this very high-risk population

Bioimpedance indices of fluid overload and cardiorenal outcomes in heart failure and chronic kidney disease: a systematic review

Background: Bioimpedance-based estimates of fluid overload have been widely studied and systematically reviewed in populations of those undergoing dialysis, but data from populations with heart failure or nondialysis chronic kidney disease (CKD) have not. Methods and Results: We conducted a systematic review of studies using whole-body bioimpedance from populations with heart failure and nondialysis CKD that reported associations with mortality, cardiovascular outcomes and/or CKD progression. We searched MEDLINE, Embase databases and the Cochrane CENTRAL registry from inception to March 14, 2022. We identified 31 eligible studies: 20 heart failure and 11 CKD cohorts, with 2 studies including over 1000 participants. A wide range of various bioimpedance methods were used across the studies (heart failure: 8 parameters; CKD: 6). Studies generally reported positive associations, but between-study differences in bioimpedance methods, fluid overload exposure definitions and modeling approaches precluded meta-analysis. The largest identified study was in nondialysis CKD (Chronic Renal Insufficiency Cohort, 3751 participants), which reported adjusted hazard ratios (95% confidence intervals) for phase angle &lt; 5.59 vs ≥ 6.4 of 2.02 (1.67–2.43) for all-cause mortality; 1.80 (1.46–2.23) for heart failure events; and 1.78 (1.56–2.04) for CKD progression. Conclusions: Bioimpedance indices of fluid overload are associated with risk of important cardiorenal outcomes in heart failure and CKD. Facilitation of more widespread use of bioimpedance requires consensus on the optimum device, standardized analytical methods and larger studies, including more detailed characterization of cardiac and renal phenotypes

Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression

Background: Acute changes in GFR can occur after initiation of interventions targeting progression of CKD. These acute changes complicate the interpretation of long-term treatment effects. Methods: To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression, enrolling 56,413 participants with at least one estimated GFR measurement by 6 months after randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable metaregression to assess the effect of intervention type, disease state, baseline GFR, and albuminuria on the magnitude of acute effects. Results: The mean acute effect across all studies was 20.21 ml/min per 1.73 m2 (95% confidence interval, 20.63 to 0.22) over 3 months, with substantial heterogeneity across interventions (95% coverage interval across studies, 22.50 to 12.08 ml/min per 1.73 m2). We observed negative average acute effects in renin angiotensin system blockade, BP lowering, and sodium-glucose cotransporter 2 inhibitor trials, and positive acute effects in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with a higher mean baseline GFR. Conclusion: The magnitude and consistency of acute GFR effects vary across different interventions, and are larger at higher baseline GFR. Understanding the nature and magnitude of acute effects can help inform the optimal design of randomized clinical trials evaluating disease progression in CKD

UK Kidney association clinical practice guideline: sodium-glucose co-transporter-2 (SGLT-2) inhibition in adults with kidney disease 2023 UPDATE

Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors. Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease. We provide a summary of the full guideline and highlight the rationale for recent updates. The use of SGLT-2 inhibitors in people with specific medical conditions, including type 1 diabetes, kidney transplants, and people admitted to hospital with heart failure is also considered, along with Recommendations for future research and Recommendations for implementation. A full “lay” summary of the guidelines is provided as an appendix to ensure that these guidelines are accessible and understandable to people who are not medical professionals

Mental health training programmes for non-mental health trained professionals coming into contact with people with mental ill health: a systematic review of effectiveness

Background The police and others in occupations where they come into close contact with people experiencing/with mental ill health, often have to manage difficult and complex situations. Training is needed to equip them to recognise and assist when someone has a mental health issue or learning/intellectual disability. We undertook a systematic review of the effectiveness of training programmes aimed at increasing knowledge, changing behaviour and/or attitudes of the trainees with regard to mental ill health, mental vulnerability, and learning disabilities. Methods Databases searched from 1995 onwards included: ASSIA, Cochrane Central Register of Controlled Clinical Trials (CENTRAL), Criminal Justice Abstracts, Embase, ERIC, MEDLINE, PsycINFO, Social Science Citation Index. Courses, training, or learning packages aimed at helping police officers and others who interact with the public in a similar way to deal with people with mental health problems were included. Primary outcomes were change in practice and change in outcomes for the groups of people the trainees come into contact with. Systematic reviews, randomised controlled trials (RCTs) and non- randomised controlled trials (non-RCTs) were included and quality assessed. In addition non-comparative evaluations of training for police in England were included. Results From 8578 search results, 19 studies met the inclusion criteria: one systematic review, 12 RCTs, three prospective non-RCTs, and three non-comparative studies. The training interventions identified included broad mental health awareness training and packages addressing a variety of specific mental health issues or conditions. Trainees included police officers, teachers and other public sector workers. Some short term positive changes in behaviour were identified for trainees, but for the people the trainees came into contact with there was little or no evidence of benefit. Conclusions A variety of training programmes exist for non-mental health professionals who come into contact with people who have mental health issues. There may be some short term change in behaviour for the trainees, but longer term follow up is needed. Research evaluating training for UK police officers is needed in which a number of methodological issues need to be addressed

Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study

Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signaling in mutant mice that have truncations at position 569 and 391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum) or no growth hormone-dependent STATS signaling respectively. These mutants result in altered liver metabolism, obesity and insulin resistance