Effectiveness of Aldosterone Blockade in Patients With Diabetic Nephropathy

Abstract—It has been reported that continuous ACE inhibitor therapy does not necessarily produce a maintained decrease in plasma aldosterone levels, which may remain high or increase eventually during long-term use (aldosterone escape). We have examined the role of aldosterone escape in 45 patients with type 2 diabetes and early nephropathy treated with an ACE inhibitor for 40 weeks. With treatment, there was a 40% reduction in average urinary albumin excretion, although urinary albumin excretion in patients with aldosterone escape (18 patients) was significantly higher than that in patients without escape (27 patients). In the 18 patients with escape, spironolactone (25 mg/d) was added to ACE inhibitor treatment in 13. After a 24-week study period, urinary albumin excretion and left ventricular mass index were significantly reduced without blood pressure change. In conclusion, the present study demonstrates that aldosterone escape is observed in 40% of patients with type 2 diabetes with early nephropathy despite the use of ACE inhibitors. Our study suggests the possibility that aldosterone blockade may represent optimal therapy for patients with early diabetic nephropathy who show aldosterone escape during ACE inhibitor treatment and who no longer show maximal antiproteinuric effects of ACE inhibition. Additional, larger, prospectively randomized, double-blind studies will be needed before adaptation of this strategy.