The addition of spironolactone or hydrochlorothiazide enhances the antialbuminuric effect of renin-angiotensin blockers. However, comparative studies on the effect of different diuretics are lacking. We conducted a prospective randomized crossover study to compare the effects of spironolactone (25 mg/day), hydrochlorothiazide (50 mg/day) without/with amiloride (5 mg/day) on top of enalapril treatment in 21 patients with CKD stages 1-3 and a urinary albumin-to-creatinine ratio (UACR) over 300 mg/g. Treatment periods lasted 4 weeks. The UACR showed a significant reduction with the diuretics: spironolactone, -34% or hydrochlorothiazide without/with amiloride -42% or -56%, respectively. Reduction of the UACR was significantly greater with hydrochlorothiazide without/with amiloride when compared with spironolactone. The percentage of patients who achieved UACR reductions greater than 30% and 50% was greater with hydrochlorothiazide without/with amiloride (81% and 57%, and 81% and 66%, respectively) when compared with spironolactone alone (57% and 28%, respectively). Glomerular filtration rate (GFR), blood pressure, and body weight decreased with the three diuretic regimens. A significant correlation was found between the UACR reduction and GFR and blood pressure changes. Thus, diverse diuretic regimens differentially enhance albuminuria reduction, an effect likely associated with the degree of GFR reduction.