title: The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease.
abstract: OBJECTIVE
  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 30-89ml/min/1.73m(2) ) received 25mg 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(+) ≥6.0mmol/L) was <1%. A potassium 5.5-5.9mmol/L occurred on ≥1 occasion over follow-up in 11 patients (nine on spironolactone) and was predicted by baseline potassium ≥5.0mmol/L and eGFR ≤45 ml/min/1.73m(2) . 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Cardiovascular Medicine Cardiology Medicine Nephrology, University Hospital and University of Birmingham, Edgbaston, Birmingham, UK. n.c.edwards@bham.ac.uk
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Edwards
authors.forename: Richard P
authors.initials: RP
authors.lastname: Steeds
authors.forename: Colin D
authors.initials: CD
authors.lastname: Chue
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ferro
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D011188:Potassium / Q000097:blood; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy*; D012720:Severity of Illness Index; D013148:Spironolactone / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D011188:Potassium