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Aldosterone Blockade Attenuates Urinary Monocyte Chemoattractant Protein-1 and Oxidative Stress in Patients with Type 2 Diabetes Complicated by Diabetic Nephropathy

Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, Koshigaya 343-8555, Japan

Address all correspondence and requests for reprints to: Kohzo Takebayashi, M.D., Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50, Minami-Koshigaya, Koshigaya 343-8555, Japan. E-mail: takeb{at}gmail.plala.or.jp.

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 (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 log₁₀-transformed (log) 8-iso-PGF2 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 or log MCP-1 were found in any group. Significant decreases in 8-iso-PGF2, 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 and that spironolactone can decrease urinary MCP-1 and oxidative stress.

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