The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease

• Published in: British journal of clinical pharmacology Vol. 73; no. 3; pp. 447 - 454
• Main Authors: Edwards, Nicola C., Steeds, Richard P., Chue, Colin D., Stewart, Paul M., Ferro, Charles J., Townend, Jonathan N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2012; Blackwell; Blackwell Science Inc
• Subjects: Adult; Aged; aldosterone; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Biological and medical sciences; Blood Pressure - drug effects; chronic kidney disease; Dose-Response Relationship, Drug; Drug Interactions; Drug Safety; Female; Follow-Up Studies; Glomerular Filtration Rate - drug effects; Humans; Hyperkalemia - chemically induced; Kidneys; Male; Medical sciences; Middle Aged; Mineralocorticoid Receptor Antagonists - adverse effects; Mineralocorticoid Receptor Antagonists - therapeutic use; mineralocorticoid receptor blockade; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Pharmacology. Drug treatments; potassium; Potassium - blood; Regression Analysis; Renal failure; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - drug therapy; Severity of Illness Index; Spironolactone - adverse effects; Spironolactone - therapeutic use; Urinary system involvement in other diseases. Miscellaneous; Kidney disease; Human; Urinary system disease; Potassium sparing diuretic; Steroid hormone; Mineralocorticoid; Toxicity; mineralocorticoid receptor blockade; Chronic kidney disease; Aldosterone; Inorganic element; Aldosterone antagonist; Spironolactone; Mineralocorticoid receptor; Adrenal hormone; Renal failure; Safety; Potassium
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/j.1365-2125.2011.04102.x

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Spironolactone has recently been shown to exert beneficial effects on the cardiovascular and renal systems. To date, its use in patients with chronic kidney disease has been limited due to potential risks of hyperkalaemia and declining renal dysfunction. WHAT THIS STUDY ADDS • Non‐diabetic patients with early stage chronic kidney disease (CKD) on concomitant therapy with angiotensin converting enzyme (ACE) inhibition or angiotensin II receptor blockade with a serum potassium of <5.5 mmol/L and no history of hyperkalaemia who were randomized in a trial to treatment with spironolactone for 40 weeks had low rates of serious hyperkalaemia (<1%) and worsening renal function (<3%). Frequent biochemical monitoring is required for the initial 4 weeks but only routine monitoring is needed thereafter. AIM Mineralocorticoid receptor blockade (MRBs) in combination with angiotensin converting enzyme (ACE) inhibitors and angiotensin‐II receptor blockade (ARBs) improve prognostic markers of cardiovascular and renal disease in early stage chronic kidney disease (CKD). Concerns relating to the safety and tolerability of MRBs in CKD may limit their use in a non clinical trial setting. METHODS In the Chronic Renal Impairment in Birmingham II study, 115 patients with non‐diabetic early stage CKD (eGFR 30–89 ml/min/1.73m2) received 25 mg daily of spironolactone for 4 weeks before randomization to continuing treatment or placebo for a further 36 weeks. All patients were on ACE inhibitors and/or ARB therapy. Potassium and renal function were checked at weeks 1, 2, 4, 8, 16, 28 and 40. The incidence of hyperkalaemia, significant renal dysfunction (reduction eGFR ≥25%) and adverse effects was assessed. RESULTS After 40 weeks of treatment the incidence of serious hyperkalaemia (K+≥6.0 mmol/L) was <1%. A potassium 5.5–5.9 mmol/L occurred on ≥1 occasion over follow‐up in 11 patients (nine on spironolactone) and was predicted by baseline potassium ≥5.0 mmol/L and eGFR ≤45 ml/min/1.73m2. Over follow‐up, three patients experienced significant renal dysfunction but no patients withdrew due to intolerance or side effects. Changes in potassium, eGFR and systolic blood pressure were most apparent in the first 4 eeks. CONCLUSION Spironolactone was well tolerated in selected patients with early stage CKD. Strict monitoring over the first month of treatment followed by standard surveillance as for ACE inhibitors and ARBs is suggested.