The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study

Diabet Med. 2004 May;21(5):471-5. doi: 10.1111/j.1464-5491.2004.01194.x.

Abstract

Objective: The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension.

Patients and methods: Sixty female diabetic patients aged 45-70 years with blood pressure (BP) 140-180/90-110 mmHg, serum creatinine (sCr) < or = 160 micro mol/l, HbA(1c) < or = 10%, and albuminuria were treated by atenolol 12.5-75 mg/d and hydrochlorothiazide 6.25-25 mg/d. Titration-to-target helped to reach BP values < or = 135/85 mmHg in 46 patients after 12 weeks. These patients were randomized to spironolactone 100 mg/d or cilazapril 5 mg/d for 24 weeks. Then both groups received spironolactone 50 mg/d and cilazapril 2.5 mg/d for 24 weeks. BP was stabilized by tapering the dose of the initial agents. Urinary albumin/creatinine ratio (ACR), BP, K(+). sCr and HbA(1c) were assessed at baseline and at weeks 12, 16, 36 and 60.

Results: The average BP at week 12 was 128 +/- 4/81 +/- 3 mmHg and remained constant, in both groups, throughout the study. ACR declined on spironolactone from a median value (range) of 452 (124-1571) to 216 (64-875) mg/g (P = 0.001), and on cilazapril to 302 (90-975) mg/g (P = 0.001). The difference between spironolactone and cilazapril was significant (P = 0.002). Combined treatment resulted in a further modest decline in ACR. Serum creatinine was unaltered by spironolactone and rose slightly (121 to 126 micro mol/l, P = 0.02) on cilazapril.

Conclusion: At the doses tested, spironolactone was superior to cilazapril in reducing albuminuria. Combined administration was more effective than either drug alone. These effects were independent of BP values. Hyperkalaemia was the main side-effect.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Retracted Publication

MeSH terms

  • Aged
  • Albuminuria / drug therapy*
  • Albuminuria / physiopathology
  • Blood Pressure / drug effects
  • Cilazapril / therapeutic use*
  • Creatinine / blood
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / physiopathology
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / analogs & derivatives*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypertension / drug therapy*
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Prospective Studies
  • Spironolactone / therapeutic use*

Substances

  • Glycated Hemoglobin A
  • Mineralocorticoid Receptor Antagonists
  • glucosylated hemoglobin A
  • Cilazapril
  • Spironolactone
  • Creatinine