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

Neutron capture reaction cross-section of 79Se through the 79Se(d,p) reaction in inverse kinematics

γ emission probabilities from unbound states in 78,80Se, populated by a neutron-transfer reaction (d,p) on 77,79Se nuclei in inverse kinematics, were measured by directly detecting reaction residues. Assuming the spin distribution at the respective excitation energy of the unbound state, the cross-sections of the 79Se(n,γ)80Se reaction were evaluated using the γ emission probabilities. The surrogate-ratio method with the experimental γ emission probabilities of 78,80Se was also employed to deduce the cross-sections of 79Se(n,γ) reaction by incorporating the theoretical evaluations of the neutron-capture reaction on the isomeric state in 77Se. Our two cross-sections are in good agreement with existing nuclear data compilations for the neutron-capture reaction on 79Se. The presented method contributes to the body of existing knowledge by providing approaches for determining the neutron capture cross-sections of radioactive nuclei at various neutron energies

Isotopic production cross sections of residual nuclei in proton-and deuteron-induced reactions on 91,92^{91,92}Y,92,93^{92,93}Zr,and93,94^{93,94}Nb around 100 MeV/nucleon

Production cross sections of residual nuclei via proton-and deuteron-induced spallation reactions on 91,92 Y, 92,93 Zr, and 93,94 Nb at projectile energies Production cross sections of residual nuclei via proton-and deuteron-induced spallation reactions on $^{91,92}$Y,$^{92,93}$Zr,and $^{93,94}$Nb at projectile energies around 100 MeV/nucleon were measured in inverse kinematics at the RIKEN Radioactive Isotope Beam Factory. Noticeable jumps in the measured cross sections of isotone production appear between the neutron numbers N =51 and 50 for target nuclei with the initial neutron number N$_{init}$ =53 ($^{92}$Y, $^{93}$Zr, and $^{94}$Nb), while such jump is not clearly seen for target nuclei with N$^{init}$=52($^{91}$Y,$^{92}$Zr, and $^{93}$Nb). The measured isotopic production cross sections are compared with PHITS calculations considering both the intranuclear cascade and evaporation processes in order to benchmark the reaction models

Proton elastic scattering at 200 A MeV and high momentum transfers of 1.7–2.7 fm−1 as a probe of the nuclear matter density of 6He

Differential cross sections of p–6He elastic scattering were measured in inverse kinematics at an incident energy of 200 AMeV, covering the high momentum transfer region of 1.7–2.7 fm−1. The sensitivity of the elastic scattering at low and high momentum transfers to the density distribution was investigated quantitatively using relativistic impulse approximation calculations. In the high momentum transfer region, where the present data were taken, the differential cross section has an order of magnitude higher sensitivity to the inner part of the 6He density relative to the peripheral part (15:1). This feature makes the obtained data valuable for the deduction of the inner part of the 6He density. The data were compared to a set of calculations assuming different proton and neutron density profiles of 6He. The data are well reproduced by the calculation assuming almost the same profiles of proton and neutron densities around the center of 6He, and a proton profile reproducing the known point-proton radius of 1.94 fm. This finding is consistent with the assumption that the 6He nucleus consists of a rigid α -like core with a two-neutron halo

Proton elastic scattering at 200 A MeV and high momentum transfers of 1.7–2.7 fm−1^{−1} as a probe of the nuclear matter density of 6^6He

International audienceDifferential cross sections of p–6He elastic scattering were measured in inverse kinematics at an incident energy of 200 A MeV, covering the high momentum transfer region of 1.7–2.7 fm−1. The sensitivity of the elastic scattering at low and high momentum transfers to the density distribution was investigated quantitatively using relativistic impulse approximation calculations. In the high momentum transfer region, where the present data were taken, the differential cross section has an order of magnitude higher sensitivity to the inner part of the 6He density relative to the peripheral part (15:1). This feature makes the obtained data valuable for the deduction of the inner part of the 6He density. The data were compared to a set of calculations assuming different proton and neutron density profiles of 6He. The data are well reproduced by the calculation assuming almost the same profiles of proton and neutron densities around the center of 6He, and a proton profile reproducing the known point-proton radius of 1.94 fm. This finding is consistent with the assumption that the 6He nucleus consists of a rigid α-like core with a two-neutron halo