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 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 m 2), 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

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 &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;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 &lt;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&lt;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&lt;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

SPANISH MULTICENTRIC STUDY ABOUT NUTRITION-INFLAMATIONhn WITH MID DILUTION (ENIMID STUDY): PRELIMINARY RESULTS

The prevalence of malnutrition are 23-76% of ESRD patients undergoing HD, and 20-50% of them suffers inflammation. Nowadays, the “malnutrition-inflammation” duo is frequently found in HD patients.The aim of this Spanish multicenter study is to evaluate the effects of the Mid-Dilution HDF on the inflammatory-nutritional state, on some body composition and on the quality of life in the HD patients. The total number of patients expected 64; the preliminary analysis of 52 patient/3 months and 23 after 6months (the study will last 1 year), is presented. Methods: Patients undergoing standard HD treatment with High Flux dialyzers for 4 hours/three times a week passed to HDF Online MidDilution with OLPUR 220 filters at a reinfusion rate of 12l/h.The patients are classified by: age, gender, Charlson comorbidity index, dialysis vintage. The parameters analyzed each 3 months are: urea, β2microglobuline, albumin, pre-albumin, CRP, fibrinogen, IL6, IL10, leptin, adiponectin, neuropeptide Y, body composition by BIVA parameters and apetite and quality life surveys. RESULTS: Patients classification: • Age: 64.06±0.8 years; • Sex: 64% male; • Charlson-index: 3.97±1.66; • HD vintage 54.7±44.8 months.Significant decrease of β2microglobuline pre-dialysis from baseline 26,16 to 20,06 mg/L (p= 0,006) after 3 months and to 17,88smg/L (p= 0.09) after 6 months. xβ2microglobulineRR was 82.45 ±3.20 % and the URR was 79.56±3.51 %, which demonstrates a good removal of medium and small molecules. The Kt/V remained stable (>1,5). Albumin increased from 3.81 g/dL to 3.87 g/dL in e months and to 3.89 g/dL in the 6 months of evaluation. No significant differences in levels of pre-albumin (xbaseline 28 mg/dl). Corporal and BIVA parameters evolution These data shown an improvement of the body composition and water distribution. .Sig. improvements were seen in the appetite scale in the first 6 months (p= 0.09). The total Quality of Life, evaluated in 3 months by SF36, increased from 55,61 to 50,66 (p= 0,05); the physic from 50,28 to 55,92 (p= 0,036); the mental from 55,69 to 60,1 (p= 0,12).Cytokines:we found an increase in neuropeptide Y and IL10 and no significant changes in leptin and adiponectin with slight increase of IL6. CONCLUSIONS: 1-The preliminary results show that MidDilution provides a good removal of small and middle molecules, increases appetite by providing a proper balance of cytokines through stimulation of antiinflamatory ones and neuropeptide Y. 2-It provides an improvement of body composition. Finally MidDilution improves nutritional parameters which leads to a better quality of life, as well as physical and mental status