Aldosterone blockade attenuates urinary monocyte chemoattractant protein-1 and oxidative stress in patients with type 2 diabetes complicated by diabetic nephropathy

Context: Aldosterone causes organic impairment by enhancement of oxidative stress and subsequent induction of proinflammatory cytokines and chemokines. Objective: This study was designed to investigate the effect of spironolactone, an aldosterone blocker, on oxidative stress and the level of urinary monocyte chemoattractant protein (MCP)-1, a cysteine-cysteine chemokine that may contribute to progression of various nephropathies in type 2 diabetic patients with diabetic nephropathy. Design, Setting, Patients and Other Participants, and Intervention: The patients were randomly assigned to two groups in which they received either spironolactone (50 mg/d; n=23) or amlodipine (2.5 mg/d; n=14). Main Outcome Measures: Urinary 8-iso-prostaglandin (PG) F2 alpha (a marker of oxidative stress), urinary MCP-1, and urinary albumin excretion (UAE) were measured at the start of administration (0 months) and after 3 months in each group. Baseline levels of these variables were also measured in 25 age-matched healthy subjects. Results: There were significant positive correlations between log(10)-transformed (log) 8-iso-PGF2 alpha and log MCP-1 levels in control and diabetic subjects and all subjects combined, but no correlations between log UAE and log 8-iso-PGF2 alpha or log MCP-1 were found in any group. Significant decreases in 8-iso-PGF2 alpha, MCP-1, and UAE were observed with spironolactone (P=0.0001, P=0.0041, and P=0.0037, respectively), and systolic blood pressure significantly decreased after both spironolactone and amlodipine therapy (P=0.00011 and P=0.0051, respectively). Conclusions: Our data suggest that urinary MCP-1 is correlated with oxidative stress as measured by urinary 8-iso-PGF2 alpha and that spironolactone can decrease urinary MCP-1 and oxidative stress.