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

Abstract

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).

Keywords: Aldosterone blockers; Diabetic kidney disease; Thiazide diuretics.

Figure 1

Changes in (a) urinary albumin‐to‐creatinine ratio (ACR) and (b) percent change from baseline in ACR during 24 weeks of treatment with spironolactone (black circles, n = 18) or trichlormethiazide (white circles, n = 15). ACR was expressed as least‐square geometric mean ± standard error (SE); change in ACR was expressed as least‐square mean ± SE. Urinary ACR significantly decreased from baseline in both groups (P < 0.001 at all time‐points). There was no significant difference in reduction of albuminuria at 24 weeks from baseline between the two groups (P = 0.270).