Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease

Experimental evidence suggests that aldosterone contributes to progressive kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor antagonists suppress the renin-angiotensin system but they do not effectively reduce plasma aldosterone. Hence, administration of aldosterone receptor antagonists may provide additional renal protection. In the present prospective randomized open-label study, we evaluated the effects of spironolactone (25mg/day for 1 year) on proteinuria and estimated glomerular filtration rate in 83 patients with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists. Eighty-two patients were treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists alone and served as controls. After 1 year of therapy, proteinuria decreased from 2.1 +/- 0.08 to 0.89 +/- 0.06 g/g creatinine (P < 0.001) in patients treated with spironolactone, but it did not change in control patients. Baseline aldosterone levels were significantly correlated with proteinuria (r=0.76, P < 0.0001), and predicted the degree of reduction in proteinuria with spironolactone (r=0.42, P < 0.0002). Baseline estimated glomerular filtration rate was similar in patients treated with spironolactone and controls (62.4 +/- 2.4 and 62.2 +/- 2.1ml/min/1.73m(2), respectively). After 1 month of therapy with spironolactone, estimated glomerular filtration rate decreased more in patients treated with spironolactone than in controls. However, by the end of 1 year the monthly rate of decrease in estimated glomerular filtration rate from baseline was lower in patients treated with spironolactone than in controls (0.323 +/- 0.044 vs 0.474 +/- 0.037ml/min/1.73m(2), P < 0.01). Spironolactone caused a significant rise in serum potassium levels ( from 4.2 +/- 0.04 at baseline to 5.0 +/- 0.05mEq/l after 12 months of treatment, P < 0.001). In conclusion, this study has shown that spironolactone may reduce proteinuria and retard renal progression in chronic kidney disease patients.