Addition of Atrasentan to Renin-Angiotensin System Blockade Reduces Albuminuria in Diabetic Nephropathy
Journal of the American Society of Nephrology, 03/15/2011
Kohan DE et al. - Atrasentan, at the doses tested i.e. 0.25, 0.75, or 1.75 mg daily, is generally safe and effective in reducing residual albuminuria and may ultimately improve renal outcomes in patients with type 2 diabetic nephropathy.
Authors examined the effect of atrasentan, a selective endothelin A receptor (ETAR) antagonist, on albuminuria.
This is a randomized, double-blind, placebo-controlled trial of subjects with diabetic nephropathy already receiving stable doses of renin-angiotensin system (RAS) inhibitors.
89 subjects with eGFR >20 ml/min per 1.73 m2 and a urinary albumin-to-creatinine ratio (UACR) of 100 to 3000 mg/g to placebo or atrasentan (0.25, 0.75, or 1.75 mg daily) for 8 weeks were assigned.
Compared with placebo, atrasentan significantly reduced urinary albumin-to-creatinine ratio (UACR) only in the 0.75- and 1.75-mg groups (P = 0.001 and P = 0.011, respectively).
Compared with the 11% reduction in the geometric mean of the UACR from baseline to final observation in the placebo group during the study, the geometric mean of UACR decreased by 21, 42, and 35% in the 0.25-, 0.75-, and 1.75-mg atrasentan groups (P = 0.291, P = 0.023, and P = 0.073, respectively).
In the placebo group, 17% of subjects achieved >=40% reduction in UACR from baseline compared with 30, 50, and 38% in the 0.25-, 0.75-, and 1.75-mg atrasentan groups, respectively (P = 0.029 for 0.75 mg versus placebo).
Peripheral edema occurred in 9% of subjects receiving placebo and in 14, 18, and 46% of those receiving 0.25, 0.5, and 1.75 mg atrasentan, respectively (P = 0.007 for 1.75 mg versus placebo).
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