Comparison of spironolactone and trichlormethiazide as add‐on therapy to renin–angiotensin blockade for reduction of albuminuria in diabetic patients

To compare the efficacy of spironolactone and trichlormethiazide, as add‐on therapy to renin–angiotensin system ( RAS ) blockade, for reduction of albuminuria in diabetic patients with chronic kidney disease ( CKD ), we conducted this randomized, open‐labeled, parallel‐group, active‐controlled, per‐protocol‐design study. Type 2 diabetic patients receiving an angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker, with persistent albuminuria (≥100 mg/g creatinine) were randomly assigned to either spironolactone (25 mg/day) or trichlormethiazide (2 mg/day). The primary outcome was the change in albuminuria at 24 weeks of treatment. In patients who completed 24 weeks of treatment with spironolactone ( n  = 18) and trichlormethiazide ( n  = 15), albuminuria decreased significantly by −57.6 ± 21.3% ( SD ) ( P  < 0.001) and −48.4 ± 27.1% ( P  < 0.001), respectively. There was no significant difference in the change in albuminuria between groups ( P  = 0.270). This pilot study suggests add‐on therapy with spironolactone or trichlormethiazide to RAS blockade may be comparably beneficial to reducing albuminuria in type 2 diabetic patients. This trial was registered with UMIN ‐ CTR (no. UMIN 8914).