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

República Dominicana y República de Haití: De una barca, dos remos. 1844-1970

In this article, we make a journey through the history of the Dominican Republic and the Republic of Haiti that share the same island, from the discovery made by Spain and from the beginning of the XVII century when rival powers to the Spanish empire such as France, England and Holland established colonies in the Caribbean. In this context of rivalry, France and Spain negotiated the possession of the island that passed from one country to the other, until, thanks to the soldiers born in the colony and who were part of the armed forces of the French empire was proclaimed, in 1804, the Republic of Haiti located in the western part of the island. In this way, two separate and completely different nations were formed on the island in terms of language, religion, culture, ethnicity and customs. This new republic invaded the eastern part of the island for 22 years, but it achieved its independence in 1844 to become the Dominican Republic. The twentieth century was influenced by the US occupation of both countries 1915 (Haiti)-1916 (Dominican Republic), the border incident of 1937, the political instability in Haiti until the arrival of the dictator François Duvalier (1957-1971), going through the first attempt at Dominican democracy (1963) and the revolution in April (1965), as well as the first term of government of Dr. Joaquín Balaguer (1966-1970), making the relations between both countries have fluctuated depending on the governments in turn on each side of the border.En este artículo hacemos un recorrido a través de la historia de la República Dominicana y la República de Haití que comparten una misma isla, a partir del descubrimiento por España y desde inicios del siglo XVII cuando potencias rivales al imperio español como Francia, Inglaterra y Holanda establecieron colonias en el Caribe. En ese contexto de rivalidad, Francia y España negociaban la posesión de la isla que pasaba de un país al otro, hasta que, gracias a los militares nacidos en la colonia y que formaban parte de las fuerzas del imperio francés se proclamó, en 1804, la República de Haití situada en la parte Oeste de la isla. De esta manera se fueron configurando en la isla dos naciones independientes y completamente diferentes en cuanto a idioma, religión, cultura, etnia y costumbres. Esta nueva república invadió la parte Este de la isla durante 22 años, pero la misma logró su independencia en 1844 para convertirse en la República Dominicana. El siglo XX fue influenciado por la ocupación estadounidense de ambos países 1915 (Haití)-1916 (República Dominicana), el incidente fronterizo de 1937, la inestabilidad política en Haití hasta la llegada del dictador François Duvalier (1957-1971), pasando por el primer intento de democracia dominicana (1963) y la revolución de abril (1965), así como del primer período de gobierno del Dr. Joaquín Balaguer (1966-1970), haciendo que las relaciones entre ambos países hayan tenido fluctuaciones dependiendo de los gobiernos de turno a cada lado de la frontera

Congreso Internacional euro-latinoamericano y caribeño: "La necesaria creación de un espacio de un espacio cultural birregional: valores, principios y propuestas"

Actas del Congreso Internacional euro-latinoamericano y caribeño: "La necesaria creación de un espacio de un espacio cultural birregional: valores, principios y propuestas" celebrado en el Monasterio de Yuste (Cáceres, España) del 22 al 24 de septiembre de 2021.El documento "Algunas miradas a la cooperación internacional en materia de cultura de 2000 a 2021 de España: Caso Colombia y Cuba / Laurita Botero Botero y Cecilia Yadira Benítez" fue realizado en el marco del proyecto de investigación y desarrollo PID 2020 No. 80020190100051UR “Agendas y actores multinivel de la cooperación internacional argentina: realizaciones y proyecciones en el primer cuarto de siglo XXI (2000-2025) de la Universidad Nacional de Rosario (Argentina), dirigido por la Dra Myriam Colacrai.Presentación / Adrián Bonilla y Cástor Díaz Barrado (p. V). -- Introducción / Diego Durán Cruz (p. VI). -- La cooperación cultural Iberoamericana. Mosaico de perspectivas, agendas y actores involucrados / Miryam Colacrai (pp. 1-5). -- Cooperación cultural: nuevos contextos y potencialidades en el ámbito birregional Europa-América Latina / Mónica García Alonso (pp. 6-10). -- La implementación de la Agenda 2030 en el ámbito cultural / Carlos R. Fernández Liesa (p. 11). -- Una visión desde Cuba sobre la necesaria creación de un espacio cultural eurolatinoamericano: valores, principios y propuestas / Juan Mendoza Díaz (pp. 12-15). -- Minorías étnicas y Constitución política de 1991 en Colombia / Roberto González Arana (pp. 16-20). -- Género y diversidad cultural: elementos clave para el fortalecimiento cultural en América Latina / Diana M. Verdiales López (pp. 21-25). -- Las expresiones del racismo moderno y racismo cordial promueven la vulneración de derechos de las minorías afrodescendientes en Colombia. Ideas para la discusión / Ivonne Samira Molinares Guerrero (pp. 26-30). -- La falta de protagonismo de la cultura en la Agenda 2030 / Sagrario Morán Blanco (pp. 31-34). -- La Carta Cultural Iberoamericana, las industrias culturales y creativas / Ana Idalia Castellanos (pp. 35-39). -- La Carta Cultural Iberoamericana: su utilidad en la cooperación Unión Europea-CELAC / Harold Bertot Triana y Elena C. Díaz Galán (pp. 40-43). -- Relaciones culturales UE-LAC: EUNIC y sus proyectos con Latinoamerica y El Caribe / Cristina Peregrina Leyva (pp. 44-59). -- Algunas miradas a la cooperación internacional en materia de cultura de 2000 a 2021 de España: Caso Colombia y Cuba / Laurita Botero Botero y Cecilia Yadira Benítez (pp. 60-70). -- El cine como expresión cultural imprescindible para la educación en Derechos Humanos en el espacio euro-latinoamericano / Andrés Felipe Ricaurte Pazmiño (pp. 71-82). -- Lo que todo iberoamericano debe conocer sobre Iberoamérica: un currículo educativo integral orientado a un pasado, presente y futuro conjunto / Izan Chalen Paredes (pp. 83-96). -- El papel de las lenguas ibéricas en la creación de un espacio iberoamericano del conocimiento / Javier Abellán (pp. 97-110). -- La cooperación cultural en el espacio eurolatinoamericano como respuesta a los retos globales del siglo XXI / Edith Ruvalcaba Galindo (pp. 111-132)

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791