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

Kidney Int. 2006 Dec;70(12):2116-23. doi: 10.1038/sj.ki.5001854. Epub 2006 Oct 11.

Abstract

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 (25 mg/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+/-2.1 ml/min/1.73 m(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+/-0.037 ml/min/1.73 m(2), P<0.01). Spironolactone caused a significant rise in serum potassium levels (from 4.2+/-0.04 at baseline to 5.0+/-0.05 mEq/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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Kidney / physiology
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / administration & dosage*
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Prospective Studies
  • Proteinuria / drug therapy*
  • Proteinuria / physiopathology
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology
  • Spironolactone / administration & dosage*
  • Spironolactone / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone