Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Afectación de la capacidad vial por estacionamiento en vía, caso de estudio : Avenida Carrera 7ma con Avenida Calle 72, Bogotá D.C.

La presente investigación busca describir el impacto generado en cuanto a la capacidad vial a causa del estacionamiento en vía de vehículos específicamente en la intersección de la Avenida Carrera 7ma con Avenida Calle 72, en la localidad de Chapinero, mediante simulaciones realizadas en la herramienta de modelación VISSIM. Pese a la planeación y las decisiones que se llevan a cabo en la gestión del sistema de movilidad en Bogotá, la ciudad se enfrenta a diario con problemáticas generadas por la congestión vehicular y la reducción de la capacidad vial, por lo que se hace necesario trabajar mancomunadamente para que a partir de diferentes estudios y análisis como éste, se planteen alternativas de planeación que permitan un mejoramiento, donde la malla vial sea proporcional al incremento del parque automotor, lo que a su vez causara un mejoramiento en la calidad de vida de los ciudadanos. Una de las causas que afecta el flujo vehicular es el irrespeto a las normas de tránsito, como la que ocurre en la Avenida calle 72, por la infracción de estacionamiento inadecuado, obstruyendo el espacio público, al no utilizar los parqueaderos autorizados en el sector, tal como lo reporta la Secretaría Distrital de Movilidad (SDM). Con relación a esta problemática se llega a la formulación de la pregunta problema que abordara el presente estudio, la cual es: ¿Cuál es la afectación a la capacidad vial por estacionamiento de vehículos en la intersección de la Avenida Carrera 7ma con Avenida Calle 72 de la localidad de Chapinero? Para responder a esta pregunta problema se partirá de diferentes estudios que brindarán información cuantitativa y cualitativa con la cual se determinarán los factores asociados al estacionamiento en vía.This research seeks to describe the impact generated in terms of road capacity due to on-street parking of vehicles specifically at the intersection of Avenida Carrera 7ma with Avenida Calle 72, in the locality of Chapinero, through simulations carried out in the modeling tool VISSIM. Despite the planning and decisions that are carried out in the management of the mobility system in Bogota, the city faces daily problems generated by traffic congestion and the reduction of road capacity, so it is necessary to work together so that from different studies and analysis such as this one, planning alternatives are proposed that allow an improvement, where the road network is proportional to the increase of the vehicle fleet, which in turn will cause an improvement in the quality of life of citizens. One of the causes that affect the flow of vehicles is the disrespect for traffic regulations, such as the one that occurs on 72nd Street Avenue, due to the infraction of inadequate parking, obstructing public space, by not using the authorized parking lots in the sector, as reported by the District Secretary of Mobility (SDM). In relation to this problem, the problem question that this study will address is: What is the impact on road capacity due to vehicle parking at the intersection of Avenida Carrera 7ma and Avenida Calle 72 in the Chapinero district? To answer this problem question, different studies will be used to provide quantitative and qualitative information to determine the factors associated with on-street parking