Spironolactone in type 2 diabetic nephropathy: Effects on proteinuria, blood pressure and renal function

Abstract

Objective: To study the effects of addition of spironolactone to angiotensin-converting enzyme (ACE) inhibition or angiotensin II (AngII) receptor antagonism on proteinuria, blood pressure (BP) and renal function in overt type 2 diabetic nephropathy.

Design: A placebo-controlled, double-blind, parallel-group trial in patients from two outpatient clinics with a follow-up of 1 year.

Methods: Type 2 diabetic patients with macroalbuminuria, despite long-term use of an ACE inhibitor or AngII receptor blocker were allocated to spironolactone, 25-50 mg once daily (n = 29) or placebo (n = 30). Urinary albumin to creatinine ratio, BP and biochemical parameters were measured at regular intervals.

Results: Five patients of the spironolactone and one of the placebo group developed hyperkalemia and had to be excluded. Compared to other patients their baseline serum creatinine [161 (123-248) versus 88 (72-170) micromol/l] and potassium concentrations (4.7 +/- 0.3 versus 4.2 +/- 0.2 mmol/l) were elevated (P < 0.001). Albuminuria decreased by 40.6% [95% confidence interval (CI) 23.4-57.8%] and BP by 7 mmHg (2-12 mmHg)/3 mmHg (1-6 mmHg) with spironolactone, but did not change with placebo. Estimated glomerular filtration rate (eGFR) during the 1-year follow-up declined on average by 12.9 ml/min per 1.73 m (9.5-16.5 ml/min per 1.73 m) in the spironolactone and by 4.9 ml/min per 1.73 m (0.8-8.9 ml/min per 1.73 m) in the placebo group (P = 0.004). This decline was progressive in the placebo but leveled off in the spironolactone group. In the spironolactone group changes in albuminuria and GFR were correlated (r = 0.48, P = 0.007).

Conclusion: Addition of spironolactone to an ACE inhibitor or AngII receptor blocker is associated with a marked and sustained antiproteinuric effect, which in part relates to the more pronounced reduction in GFR.