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

Molecular and morphological characterization of <i>Moniliophthora roreri</i> isolates from cacao in Ecuador

<p><i>Moniliophthora roreri</i> – the causal agent of frosty pod rot (FP) disease – is one of the most devastating cacao pathogens in Ecuador and worldwide. The centre of diversity of this pathogen is believed to be in areas near Ecuador or Colombia but molecular, morphological and growth studies of this pathogen in Ecuador are scarce. Monosporic cultures of <i>M. roreri</i> from the six cacao-producing regions of Ecuador, including Esmeraldas, El Oro, Los Rios, Guayas, Manabi and Amazon were obtained. Morphological characteristics, such as mycelial growth, colony shape, colour and texture, as well as type and size of meiospores, were recorded for each isolate. Molecular variation was assessed by direct sequencing the ITS1, 5.8 s, and ITS2 rDNA regions as well as by RFLP analyses on the same regions. Results showed little variation of morphological traits across isolates. Mycelial growth rate fitted to a Gompertz model with parameters estimates that were significantly affected by mycelial colour. Molecular analysis data showed an average polymorphism of 48.98% and Shannon’s diversity index of 0.21. Multiple discriminant analyses carried out on the RFLP patterns showed a 100% accurate grouping by both sampling province and mycelial colour.</p