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

Influencia de la formulación de la glutamina en sus efectos sobre los sistemas antioxidantes y de destoxificación hepática en la rata

Objetivos: El objeto de este estudio es valorar el efecto que la suplementación de dietas parenterales con L-gluta-mina o con L-alanil-L-glutamina ejerce sobre el equilibrio oxidante/antioxidante hepático y sobre los sistemas de destoxificación mediados por el citocromo P-450 en ratas. Material y métodos: Los animales (n = 60) se cateterizaron centralmente y se asignaron aleatoriamente a uno de los siguientes grupos: grupo control con alimentación oral e infusión i.v. de solución salina (C), grupo de nutrición parenteral total sin glutamina (NPT sin GLN), grupo de nutrición parenteral suplementada con glutamina (NPT GLN) y grupo de nutrición parenteral total suplementada con dipéptido alanina-glutamina (20 g/L) (NPT ALA-GLN). Las nutriciones parenterales eran isocalóricas e isonitrogenadas y las infusiones se administraron a una velocidad de infusión de 2 ml/h durante 5 días. Resultados: En los animales del grupo sin GLN disminuyó la concentración hepática de glutatión y los niveles de los productos de reacción del ácido tiobarbitúrico (TBARS) se incrementaron. Tanto la suplementación con glutamina como con alanina-glutamina normalizaron los niveles de glutatión pero sólo en el grupo del d-péptido disminuyeron los niveles de TBARS. Este efecto era paralelo a la recuperación parcial de las actividades enzimáticas antioxidantes analizadas. La concentración hepática del citocromo P-450, de las monooxigenasas dependientes del citocromo P-450 y el aclaramiento de antipirina no se modificaron por la suplementación de glu-tamina o de alanina-glutamina. Conclusiones: Nuestros datos sugieren una mayor protección de la suplementación con alanina-glutamina contra el daño producido por radicales libres durante la NPT y una ausencia de efectos tanto de la suplementación con glutamina como con alanina-glutamina sobre el metabolismo oxidativo hepático

Autochthonous acute hepatitis E: an increasingly frequent diagnosis. Clinical-epidemiological analysis of our experience

Background: In Europe, acute hepatitis caused by the hepatitis E virus (HEV) traditionally was an infection found in people who had travelled to endemic zones, mainly Asia and Africa. However, a growing number of sporadic autochthonous cases are now being diagnosed in the Western world. Objective: To analyze the cases of acute HEV hepatitis diagnosed in our setting, with the identification of the clinical-epidemiological characteristics. Material and methods: We included the cases of acute HEV hepatitis diagnosed (positive anti-HEV IgM and/or HEV RNA present in serum) between January 2008 and December 2014. Different clinical, epidemiological and evolutive parameters were analyzed. Results: A total of 23 patients were identified, all originating from Spain. Fourteen cases (60.87%) presented jaundice and marked cytolysis at the time of diagnosis (aspartate aminotransferase [AST] 1,106.91 U/l and alanine aminotransferase [ALT] 1,407.04 U/l). Twenty-two cases were regarded as autochthonous, and one patient had travelled to China three months before. The mean time to resolution was 11.2 weeks. Some autoimmune markers were positive in 43.5% of the patients. Two subjects were diagnosed with previous chronic liver disease and were classified as "acute-on-chronic liver failure" (ACLF), one died and the other underwent liver transplantation. Conclusion: Acute HEV hepatitis in our setting is an autochthonous condition that is probably underdiagnosed, manifesting with jaundice and cytolysis. Autoimmune marker positivity is an epiphenomenon, which in some cases complicates the diagnosis