Kidney proteomic analysis in patients with diabetic nephropathy Ariela Benigni
Mario Negri Institute for Pharmacological Research Bergamo, Italy
TYPE 2 DIABETES MELLITUS IS A PUBLIC HEALTH CONCERN People with diabetes: (2004-2030) * In million subjects Developed Developing THE FACT 40 % of type 1 and of type 2 diabetics are at risk of overt nephropathy CARDIOVASCULAR EVENTS ARE PREDICTED BY RENAL INSUFFICIENCY 1,120,295 adults2.84 years follow-upRate of events Estimated GFR (ml/min/1.73m2) Insulin resistance/endothelial dysfunction Albuminuria Unselective proteinuria Normoalbuminuria UAE µg/min < 20 20 - 200 > 200 TYPE 2 DIABETIC ESRD INCIDENCE RATE Changes from 1991 to 2000 (US)
Coresh et al., Nephrology Self-Assessment Program, 20056
BENEDICT Normoalbuminuria UAE µg/min < 20 20 - 200 > 200
The BENEDICT trial Screened patients: 6.500 Included: 1.200 Placebo (30 events) (%) Trandolapril plus verapamil Cumulative incidence of microalbuminuria (17 events) Follow-up (months) Ruggenenti et al., N Engl J Med, Normoalbuminuria UAE µg/min < 20 20 - 200 > 200
DEMAND: The Delapril and Manidipine for Nephroprotection
A multicenter, prospective, randomized, double-blind, placebo-controlled, study in type 2 diabetic patients with hypertension
380 patients stratified according to normo- or microalbuminuria
Normoalbuminuria UAE µg/min < 20 20 - 200 > 200 VARIETY Trial
A prospective, randomized, open-label blinded end point trial to evaluate whether, at comparable blood pressure control, combined therapies with the ACE inhibitor benazepril and the angiotensin II receptor blocker valsartan, reduce the incidence of microalbuminuria more effectively than benazepril or valsartan alone in hypertensive patients with type 2 diabetes and high-normal albuminuria
Normoalbuminuria UAE µg/min < 20 20 - 200 > 200 VALID Trial
A randomized trial to assess the effects, at comparable blood pressure control, of dual renin-angiotensin blockade (RAS) by benazepril and valsartan combination therapy, as compared to single RAS blockade by benazepril or valsartan alone on ESRD and cardiovascular events in high-risk patients with type 2 diabetes and overt nephropathy.
VARIETY, VALID trials
To characterize robust biomarkers that would help to identify patients with type 2 diabetes at risk of progressive renal injury and related cardiovascular events as well as for assessing response to treatment
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