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).
ABSTRACT
Tea catechins, a class of flavonoids, are suggested to have biological effects, possibly mediated through their antioxidative properties. Recent data indicated that tea catechins suppressed proliferative changes in glomeruli and inhibited the development of glomerulosclerosis in partially nephrectomized rats. We thus sought to determine whether tea catechins may protect against renal dysfunction in streptozotocin-induced diabetic rats. Four groups of male Sprague-Dawley rats (n=11-15 per group), with and without streptozotocin-induced diabetes, were treated with and without catechins (5 mg/day) administered in the drinking water for 12 weeks. At the end of the treatment period, 24-hour urinary albumin excretion rate (AER), serum lipid peroxides as thiobarbituric acid reactive substrates (TBARS) and blood pressure were measured. Renal glomerular volume and interstitial fibrosis were assessed morphologically. Albuminuria developed progressively in untreated diabetic rats, resulting in a mean AER of 559+/-124 (mean+/-SE) versus 63+/-7 microg/day/100 g body weight in non-diabetic rats at 12 weeks (P<0.001). Catechin treatment significantly reduced AER to 287+/-56 microg/day/100 g body weight in diabetic rats (P=0.017 versus untreated diabetic rats). Increased interstitial fibrosis in the kidney, observed in untreated diabetic rats, was completely normalized with catechin treatment. Serum levels of TBARS and blood pressure were comparable among the four groups. In conclusion, administration of tea catechin retards the progression of functional and morphological changes in the kidney of streptozotocin-induced diabetic rats.
