Objective: To investigate whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors further decreases albuminuria in patients with type 2 diabetes mellitus (DM).
Methods: We conducted a prospective open-label trial in patients recruited at the Cleveland Clinic between February 2004 and November 2006. Patients with type 2 DM were eligible if they were older than 18 years of age, had been treated with any ACE inhibitor for longer than 1 month, and had a random urinary albumin to creatinine ratio (ACR) greater than 100 mg/g within 1 month of study entry. Based on screening ACR, patients were assigned to a microalbuminuria group (ACR 100-300 mg/g) or a macroalbuminuria group (ACR >300 mg/g). Patients were followed up for 12 weeks, with 4 clinic visits, 4 weeks apart. At visit 2, spironolactone, 25 mg once daily, was initiated and continued for 4 weeks. At visit 3, spironolactone was discontinued. Clinical information was obtained at each visit as were serum chemistries and 24-hour urinary albumin excretion.
Results: Twenty-four patients with type 2 DM and albuminuria completed the study. Eleven patients had microalbuminuria and 13 had macroalbuminuria. Following treatment with spironolactone, urinary albumin excretion dropped from a mean +/- SD of 404.6 +/- 60.9 mg/d to 302.7 +/- 52.7 mg/d (25.7% decrease, P<.001). In the microalbuminuria and macroalbuminuria groups, the urinary albumin excretion dropped 27.2% (P = .05) and 24.3% (P = .02), respectively. Despite a significant decrease in systolic blood pressure between visits 2 and 3 (141.2 +/- 3.5 to 132.5 +/- 3.6 mm Hg; P = .002), this change did not correlate to the change in albuminuria (r(2) = 0.02; P = .23). There were no withdrawals due to hyperkalemia.
Conclusion: Spironolactone is effective in further decreasing albuminuria in patients with type 2 DM who are already treated with ACE inhibitors.