In patients with CKD, aldosterone antagonists have been shown to decrease urine albumin excretion when added to ACE-I or ARB therapy. In the largest relevant RCT available involving CKD patients with elevated urine albumin levels and type 2 diabetes, 177 patients received eplerenone (either 50 or 100 mg daily) and 91 patients received placebo.106 The addition of eplerenone to enalapril (20 mg/day) resulted in a reduction in AERs of 40 to 50% by 12 weeks in the eplerenone groups, but by o10% in the placebo group. The greater reduction in AER in the CKD patients receiving an aldosterone antagonist in addition to an ACE-I or ARB is consistent with the findings of many smaller trials.103,107,108 Small reductions in GFR and systolic BP have also been reported. Hyperkalemia is a risk, but may have been mitigated by the concurrent use of a thiazide diuretic according to the smaller studies. Thiazide diuretics, however, were not used in the larger RCT cited above and the risk of hyperkalemia was similar among participants receiving enalapril alone and those receiving the combination of eplerenone and enalapril in that trial.106 It is premature to draw a definite conclusion as to whether aldosterone antagonists through their anti-albuminuric, anti-hyperten- sive, or anti-fibrotic effects reduce the rate of decline in kidney function in the long term. This is an area for future Drug combinations. Aldosterone antagonists are potas- sium-sparing diuretics and thus may be combined with thiazide or loop diuretics that enhance potassium loss in the urine. Great care should be exercised when aldosterone antagonists are combined with ACE-Is, ARBs, or other potassium-sparing diuretics. There is little information regard- ing the combination of aldosterone antagonists with NSAIDs or COX-2 inhibitors, but as with ACE-Is and ARBs, caution is warranted. 