Antagonists of Aldosterone and Proteinuria in Patients With CKD: An Uncontrolled Pilot Study

Background: Experimental evidence suggests that aldosterone may contribute to progressive kidney disease. Although angiotensin-converting enzyme (ACE) inhibitors and angiotensin type 1 receptor antagonists (ARBs) suppress the renin-angiotensin system, these agents do not adequately control plasma aldosterone levels. Hence, administration of aldosterone receptor antagonists may provide additional renal benefits to the ACE inhibitors and ARBs. Methods: In the present uncontrolled pilot study, we evaluate the short-term (8 weeks) effects of spironolactone on proteinuria in 42 patients with chronic kidney disease (CKD) already treated with ACE inhibitors and/or ARBs. Results: Spironolactone (25 mg/d for 8 weeks) decreased proteinuria from protein of 2.09 ± 0.16 to 1.32 ± 0.08 g/24 h after 2 weeks and 1.05 ± 0.08 g/24 h after 8 weeks. Four weeks after discontinuation of spironolactone therapy, proteinuria returned to close to baseline values. Baseline proteinuria correlated significantly with plasma aldosterone level (r = 0.81; P < 0.0001). Moreover, baseline aldosterone level correlated significantly with degree of reduction in proteinuria after treatment with spironolactone (r = 0.70; P < 0.0001). Spironolactone caused a significant increase in serum potassium levels (from 4.4 ± 0.1 mEq/L [mmol/L] at baseline to 4.8 ± 0.1 mEq/L [mmol/L] after 8 weeks of treatment; P < 0.01). Conclusion: This study shows that spironolactone may effectively reduce proteinuria in patients with CKD. Concerns remain in regard to the risk for hyperkalemia in patients with CKD. Prospective randomized trials are necessary to confirm the efficacy and safety of antagonists of aldosterone on proteinuria and progression of CKD.