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. UMIN000008914).