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

Health science

vii, 706 p. ; 25 cm

Long-term road salting effects on dispersion of organic matter from roadside soils into drainage water

Sodium chloride has been utilised for decades to maintain road safety in winter and some of its detrimental impacts have been well-documented. However, research on the organic fraction of roadside soils has concentrated upon short-term salt-effects. We hypothesise that decades of past leaching and enhanced mineralisation of organic matter have reduced the concentrations of dissolved organic carbon (DOC) flushes currently occurring. We have examined the effects of salt concentration on organic matter mobilisation in soils that have already experienced varying degrees of exposure to road salting in the field over decades. Applications of salt at concentrations experienced in the field have been simulated to quantify the extent that DOC and dissolved organic nitrogen (DON) are still being mobilised for three prior salt-impact scenarios. A balance occurs between the effects on organic matter of long-term soil pH increase (due to continued cation exchange during salt exposure) which enhances its solubility and organic matter mineralisation, short-term pH suppression (due to the mobile anion effect in soil solution) which reduces its solubility, and short- and long-term sodium-induced dispersion. This now determines the influence of road salt on organic matter leaching from roadside soils and into associated drainage waters

Extracellular nucleotide derivatives protect cardiomyocytes against hypoxic stress.

Extracellular nucleotides have widespread effects and various cell responses. Whereas the effect of a purine nucleotide (ATP) and a pyrimidine nucleotide (UTP) on myocardial infarction has been examined, the role of different purine and pyrimidine nucleotides and nucleosides in cardioprotection against hypoxic stress has not been reported.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Conductividad hidráulica en un suelo aluvial en respuesta al porcentaje de sodio intercambiable Saturated hydraulic conductivity of an alluvial soil with different exchangeable sodium percentages

El efecto del porcentaje de sodio intercambiable (PSI) sobre la conductividad hidráulica de un suelo saturado, fue estudiado en condiciones de laboratorio a través de la determinación de las relaciones entre la conductividad hidráulica medida en un suelo normal y las medidas en suelos con diferentes PSI. Los resultados muestran una gran reducción de la conductividad hidráulica con el aumento de sodio en el suelo, llegando esta reducción a ser en las muestras más sodificadas de casi 100%, cuando comparadas con las muestras sin sodio, hecho probablemente acontecido debido al efecto dispersante del sodio sobre las partículas del suelo.<br>The effect of different exchangeable sodium percentages (ESP) on the saturated hydraulic conductivity of a soil was studied under laboratory conditions by determining the relationship between the hydraulic conductivity of a normal soil and that measured on soil with different ESP. The results show a great reduction in the saturated hydraulic conductivity with the increase of the exchangeable sodium percentage in the soil, this reduction being as great as 100% on the highly sodified samples when compared with those which did not receive sodium treatment. This fact is explained due to the dispersing effect of the exchangeable sodium on the soil particles