Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

FC 096THE EFFECT OF INCREMENTAL START OF HAEMODIALYSIS ON BLOOD PRESSURE AND INTERDIALYTIC WEIGHT GAIN: PRELIMINARY FINDINGS FROM THE ENDURE STUDY

Abstract Background and Aims Mortality rates are high in patients starting haemodialysis/haemodiafiltration (HD) therapy. Incremental HD may help reduce this risk by reducing the burden of early treatment whilst patients are still adapting to long-term HD therapy. A feasibility study (ENDURE study – Clinical trials ID: NCT04268264) is being conducted with the primary objectives of evaluating the acceptability and tolerance of a new incremental HD regime. Its secondary aims are to evaluate the impact of this form of incremental HD on indicators of patient safety and wellbeing. These indicators include blood pressure (BP) control and interdialytic weight gains (IDWG) which are independently associated with adverse cardiovascular outcomes in patients on long-term HD. We present preliminary findings from the study related to systolic BP and IDWG. Method The ENDURE study is being carried out at a tertiary care hospital in the United Kingdom. Patients aged &amp;gt; 18 years known to renal services for at least 90 days, referred for start of HD, were eligible for participation. Following approved consenting procedures, they are started on a new regime of incremental HD starting dialysis twice weekly with progressive increases in the duration and frequency of sessions over 15 weeks. This period is split in to four phases; phase 1 representing the first two days of dialysis (baseline) whereas phases 2 – 4 representing the pre-specified incremental steps. Propensity scores were calculated to match each participant (incremental HD group) with two controls from a database of patients who previously started HD at our centres using the standard protocol of 3 times weekly, 4hr long sessions. The matching criteria accounted for 14 key demographic, clinical and laboratory characteristics. Results were analysed as intention to treat. In comparing BP and IDWG between the two groups, only readings taken pre-dialysis at the first session of the week was considered. This study has been approved by the West of Scotland Research Ethics committee-4 (Ref: 19/WS/0019). Results Baseline characteristics of the first 15 participants (target 20) and their matched controls are presented in table 1. The proportion of females and duration of previous specialist input was higher in the incremental HD group. Conclusion The ENDURE study tests the feasibility of starting patients on a novel incremental HD regime. Early data suggest that control of systolic BP and IDWG are comparable to patients who start dialysis at 3 times weekly. Further work is needed to understand the impact of reducing dialysis frequency on BP control correlating the findings with changes residual renal function and objective measures of fluid overload. </jats:sec

“We were not merely participating; we were leading the discussions”: Participation and self-representation of refugee young people in international advocacy

There is increased commitment to the participation and self-representation of people with lived experiences as refugees and asylum seekers in advocacy, especially at international, high-level events. However, we know very little about what opportunities and challenges such processes present. This paper reports on findings from a research project on youth participation and self-representation at the United Nations High Commissioner for Refugees (UNHCR) in collaboration with two young women and two young men from refugee backgrounds who live in Australia. We contribute new perspectives to contemporary debates on the potential for participation and self-representation in high-level consultations to effect policy change

Status and perspective of concentrating photovoltaic systems: The results of the BioCPV project and opportunities for a sustainable energy supply to rural areas

The present paper reports the results of the BioCPV project, a venture of six universities conceived to develop a novel integrated renewable energy system for an autonomous electrical power generation for rural electrification. Concentrating Photovoltaics (CPV) is coupled to an Anaerobic Digestion Biogas system through a smart control mechanism to maximize the efficiency and to supply electricity uninterruptedly. The excess electricity generated during the day time is used to generate hydrogen, stored using metal hydride technologies and released during evening hours as input of an electricity generator. The waste heat of the CPV is recovered and used to accelerate the biogas production. The outcomes of the research on concentrating photovoltaic technologies are resumed: two high-concentrating systems have been developed, different thermal and electrical models have been proposed and the results of innovative researches on optics, building-integration and cooling have been presented