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

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) mu mol/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 (CO 23.4-57.8%] and BP by 7 mmHg (2-12 mmHg)/3 mmHg (11-6 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(2) (9.5-16.5 ml/min per 1.73 m(2)) in the spironolactone and by 4.9 ml/min per 1.73 m(2) (0.8-8.9 ml/min per 1.73 m(2)) 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.