Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Vegetation recovery and plant facilitation in a human-disturbed lava field in a megacity: searching tools for ecosystem restoration

Unplanned urban development threatens natural ecosystems. Assessing ecosystem recovery after anthropogenic disturbances and identifying plant species that may facilitate vegetation regeneration are critical for the conservation of biodiversity and ecosystem services in urban areas. At the periphery of Mexico City, illegal human settlements produced different levels of disturbance on natural plant communities developed on a lava field near the Ajusco mountain range. We assessed natural regeneration of plant communities 20 years after the abandonment of the settlements, in sites that received low (manual harvesting of non-timber forest products), medium (removal of aboveground vegetation), and high (removal of substrate and whole vegetation) disturbance levels. We also tested the potential facilitative role played by dominant tree and shrub species. Plant diversity and vegetation biomass decreased as disturbance level increased. Sites with high disturbance level showed poor regeneration and the lowest species similarity compared to the least disturbed sites. Six dominant species (i.e., those with the highest abundance, frequency, and/or basal area) were common to all sites. Among them, three species (the tree Buddleja cordata, and two shrubs, Ageratina glabrata and Sedum oxypetalum) were identified as potential facilitators of community regeneration, because plant density and species richness were significantly higher under their canopies than at open sites. We propose that analyzing community structural traits of the successional vegetation (such as species diversity and biomass) and identifying potential facilitator species are useful steps in assessing the recovery ability of plant communities to anthropogenic disturbances, and in designing restoration strategies

Cross-continental comparison of safety and protection measures amongst urologists during COVID-19

Objectives To determine the well-being of urologists worldwide during the coronavirus disease 2019 pandemic, and whether they have adequate personal protective equipment knowledge and supplies appropriate to their clinical setting. Methods Urologists worldwide completed a Societe Internationale d'Urologie online survey from 16 April 2020 until 1 May 2020. Analysis was carried out to evaluate their knowledge about protecting themselves and others in the workplace, including their confidence in their ability to remain safe at work, and any regional differences. Results There were 3488 respondents from 109 countries. Urologists who stated they were moderately comfortable that their work environment offers good protection against coronavirus disease 2019 showed a total mean satisfaction level of 5.99 (on a "0 = not at all" to "10 = very" scale). A large majority (86.33%) were confident about protecting themselves from coronavirus disease 2019 at work. However, only about one-third reported their institution provided the required personal protective equipment (35.78%), and nearly half indicated their hospital has or had limited personal protective equipment availability (48.08%). Worldwide, a large majority of respondents answered affirmatively for testing the healthcare team (83.09%). Approximately half of the respondents (52.85%) across all regions indicated that all surgical team members face an equal risk of contracting coronavirus disease 2019 (52.85%). Nearly one-third of respondents reported that they had experienced social avoidance (28.97%). Conclusions Our results show that urologists lack up-to-date knowledge of preferred protocols for personal protective equipment selection and use, social distancing, and coronavirus disease 2019 testing. These data can provide insights into functional domains from which other specialties could also benefit.SIU Central Offic

Cross‐continental comparison of safety and protection measures amongst urologists during COVID‐19

Objectives To determine the well-being of urologists worldwide during the coronavirus disease 2019 pandemic, and whether they have adequate personal protective equipment knowledge and supplies appropriate to their clinical setting. Methods Urologists worldwide completed a Societe Internationale d'Urologie online survey from 16 April 2020 until 1 May 2020. Analysis was carried out to evaluate their knowledge about protecting themselves and others in the workplace, including their confidence in their ability to remain safe at work, and any regional differences. Results There were 3488 respondents from 109 countries. Urologists who stated they were moderately comfortable that their work environment offers good protection against coronavirus disease 2019 showed a total mean satisfaction level of 5.99 (on a "0 = not at all" to "10 = very" scale). A large majority (86.33%) were confident about protecting themselves from coronavirus disease 2019 at work. However, only about one-third reported their institution provided the required personal protective equipment (35.78%), and nearly half indicated their hospital has or had limited personal protective equipment availability (48.08%). Worldwide, a large majority of respondents answered affirmatively for testing the healthcare team (83.09%). Approximately half of the respondents (52.85%) across all regions indicated that all surgical team members face an equal risk of contracting coronavirus disease 2019 (52.85%). Nearly one-third of respondents reported that they had experienced social avoidance (28.97%). Conclusions Our results show that urologists lack up-to-date knowledge of preferred protocols for personal protective equipment selection and use, social distancing, and coronavirus disease 2019 testing. These data can provide insights into functional domains from which other specialties could also benefit.SIU Central Offic