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

Spatial synchrony in Drosophila suzukii population dynamics along elevational gradients

1. Spotted wing drosophila (SWD; Drosophila suzukii Matsumura, 1931) is a polyphagous invasive crop pest native of Southeast Asia able to attack a wide array of host plant species in both cultivated and natural habitats. SWD is now widespread in several mountain regions, but it is still unclear how the species moves to different elevations across the seasons, and how this depends on environmental conditions and food resources. 2. The temporal dynamics of several SWD populations were studied along elevational gradients in the Alps using a synchrony analysis. Twelve transects were selected, covering an overall elevational gradient of 2100 m. SWD abundance was monitored every 2 weeks during the growing season (from June to November 2015) when cultivated and wild hosts are potentially susceptible (i.e. fruits are ripe). 3. Spotted wing drosophila were widely distributed along all the tested elevations, revealing synchrony in population dynamics across ranges in elevation and geographic distance. Synchronised populations were observed at distances of up to 100 km at sites with similar temperatures. The high dispersal potential of the pest together with the seasonal variation in temperature are likely to be the dominant mechanisms causing the observed spatial synchrony. A factor that seemed to reduce synchrony is the large concentration of host plants (i.e. crop) in lowland agricultural landscapes. 4. The spatial synchrony in pest abundance at large spatial scale indicates that the risk of SWD outbreaks is highly dependent on drivers beyond the control of traditional field-scale management. These findings could help in developing monitoring and predictive models of SWD population dynamics

Ocular Tolerability of Bimatoprost 0.1 mg/mL Preservative-Free versus Bimatoprost 0.1 mg/mL with Benzalkonium Chloride or Bimatoprost 0.3 mg/mL Preservative-Free in Patients with Primary Open-Angle Glaucoma

Abstract: This study aimed to evaluate whether the therapeutic switch from a formulation of Bimato- prost 0.1 mg/mL with benzalkonium chloride (BAK) or Bimatoprost 0.3 mg/mL preservative-free to a formulation of Bimatoprost 0.1 mg/mL preservative-free could improve eye surface conditions in patients with glaucoma; intraocular pressure (IOP) was also evaluated. All patients meeting the inclusion criteria were eligible for the therapeutic switch to Bimatoprost 0.1 mg/mL preservative- free. At each check visit, enrolled patients underwent a break-up time (BUT) test, an ocular surface disease index (OSDI) test, and a three-point tonometric curve. A total of 40 patients were enrolled (23 were in therapy with Bimatoprost 0.1 mg/mL with BAK and 17 with Bimatoprost 0.3 mg/mL preservative-free). Significant differences of OSDI and BUT between Bimatoprost 0.1 mg/mL with BAK at baseline vs. Bimatoprost 0.1 mg/mL preservative-free at 14 and 28 days (p < 0.0001 and p = 0.0003, respectively) were recorded. Similarly, significant differences of OSDI and BUT between Bimatoprost 0.3 mg/mL preservative-free at baseline vs. Bimatoprost 0.1 mg/mL preservative-free at 14 and 28 days (p < 0.0001 for both) were found. Bimatoprost 0.1 mg/mL preservative-free has a better tolerability profile associated with non-therapeutical inferiority in the control of IOP compared to the other Bimatoprost formulations

Impact of Brightness on Choroidal Vascularity Index

The use of choroidal vascularization to diagnose and follow-up ocular and systemic pathologies has been consolidated in recent research. Unfortunately, the choroidal parameters can be different depending on the lighting settings of optical coherence tomography (OCT) images. The purpose of this study was to examine whether the brightness of OCT images could influence the measurements of choroidal parameters obtained by processing and analyzing scientific images with the ImageJ program. In this observational, prospective, non-randomized study, 148 eyes of 74 patients with a mean age of 30.7 ± 8.5 years (ranging from 23 to 61 years) were assessed. All patients underwent a complete ophthalmological examination including slit lamp, fundus oculi, ocular biometry, corneal tomography and spectral domain (SD) OCT evaluations of the foveal region in the enhanced depth imaging (EDI) mode. OCT images at two different brightness levels were obtained. The total choroidal area (TCA), choroidal vascularity index (CVI), stromal choroidal area (SCA) and luminal choroidal area (LCA) at both lower and higher brightness levels were measured. To avoid the bias of operator-dependent error, the lower and higher brightness TCAs were obtained using two methods: the manual tracking mode and fixed area. At the two different brightness levels, LCA, SCA and CVI measurements showed statistically significant changes (p p > 0.05). According to the results of this study, highlighting that brightness could affect LCA, SCA and CVI parameters, care should be taken during OCT image acquisition

Indications for renal biopsy in patients with diabetes. Joint position statement of the Italian Society of Nephrology and the Italian Diabetes Society

Aims: This joint document of the Italian Society of Nephrology and the Italian Diabetes Society reviews the main indications to perform a renal biopsy in diabetic patients, according to the recommendations of a panel of experts based on all available scientific evidence. Data synthesis: Renal biopsy has a pivotal role in assessing the nature and severity of renal injury in patients with diabetic kidney disease (DKD). The procedure is mandatory in the presence of one of more of the following features: rapid onset or progression of albuminuria or sudden onset of nephrotic syndrome, rapid GFR decline with or without albuminuria, hematuria, active urine sediment, clinical and/or laboratory suspicion of other systemic diseases, and, in patients with type 1 diabetes, short diabetes duration and absence of retinopathy. Indeed, ~40% of diabetic individuals with kidney injury undergoing renal biopsy are affected by a non-diabetic renal disease (NDRD). Furthermore, the histological evaluation of patients with suspected classical diabetic nephropathy allows to define the extent of glomerular, tubulo-interstitial and vascular lesions, thus providing important prognostic (and potentially therapeutic) data. In the future, the indications for renal biopsy might be extended to the definition of the histological lesions underlying the \u201cnonalbuminuric\u201d DKD phenotypes, as well as to the evaluation of the response to treatment with the new anti-hyperglycemic drugs that provide cardiorenal protection. Conclusions: In view of the heterogeneous clinical presentation and course of DKD and of the related heterogeneous histopathological patterns, a more extensive use of renal biopsy may be crucial to provide valuable information with important pathogenic, diagnostic, prognostic, and therapeutic implications

Indications for renal biopsy in patients with diabetes. Joint position statement of the Italian Society of Nephrology and the Italian Diabetes Society

This joint document of the Italian Society of Nephrology and the Italian Diabetes Society reviews the main indications to perform a renal biopsy in diabetic patients, according to the recommendations of a panel of experts based on all available scientific evidence

Lemierre's syndrome complicated by cerebral venous sinus thrombosis: A life threatening and rare disease successfully treated with empiric antimicrobial therapy and conservative approach

Lemierre's syndrome (LS) is a "forgotten" condition characterized by septic thrombophlebitis of the jugular vein that follows an otolaryngological infection. Fusobacterium necrophorum is the aetiological agent responsible for the syndrome in adolescents and young adults whereas in older people even common bacteria are involved. Complications arise from spreading of septic emboli distally, i.e. to the brain, lungs, bones and internal organs everywhere in the body. We report a middle-aged woman who presented with headache and bilateral sixth cranial nerve palsy following a sphenoidal sinusitis and left mastoiditis. Imaging revealed thrombotic involvement of the left internal jugular vein as well as of several cerebral venous sinuses thrombosis (CVT). Currently, precise management protocols of LS with CVT complication do not exist although a combination of macrolides and second or third-generation cephalosporins, as well as anti-coagulants represent the mainstream of therapeutics. Surgical drainage is associated to remove septic foci but is burdened by severe complications and side effects. Complete recovery was achieved following pharmacological treatment in our patient. This report adds further evidence that LS complicated by CVT may be effectively treated adopting a conservative approach thus avoiding surgical drainage and severe complications