Albuminuria response to very high-dose valsartan in type 2 diabetes mellitus

OBJECTIVE: Renin-angiotensin system blockade is now standard in the management of the patient with type 2 diabetes mellitus. We aimed to investigate whether high doses of valsartan, an angiotensin receptor blocker, are superior to conventional doses to reduce urinary albumin excretion rates (UAER) in such patients. PATIENTS AND METHODS: Three hundred and ninety-one hypertensive patients with type 2 diabetes mellitus and UAER 20-700 μg/min were randomized to 160, 320 or 640 mg valsartan. All received valsartan 160 mg for the first 4 weeks. Valsartan dose was then increased in two of three groups for 30 weeks. Overnight urine collections at baseline, 4, 16, and 30 weeks in triplicate were used to assess proteinuria. RESULTS: Comparable albuminuria reductions occurred in all groups at week 4 (P <0.001). Subsequently, a highly significant albuminuria fall occurred with valsartan 320 and 640 mg (P <0.001) versus a modest additional change with 160 mg (P = 0.03). At week 30, twice as many patients returned to normal albuminuria with valsartan 640 mg versus 160 mg (24 versus 12%; P <0.01). High doses were well tolerated, with no dose-related increases in adverse events, including hypotension and hyperkalemia. CONCLUSION: High doses of valsartan reduced albuminuria more than the more commonly used 160 mg dose, apparently independent of blood pressure. Thus, at least in type 2 diabetes mellitus, higher doses of valsartan are required to optimize tissue protection than for blood pressure control.