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


METHODS
Urinary 8-iso-prostaglandin (PG) F2alpha (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-PGF2alpha and log MCP-1 levels in control and diabetic subjects and all subjects combined, but no correlations between log UAE and log 8-iso-PGF2alpha or log MCP-1 were found in any group. Significant decreases in 8-iso-PGF2alpha, 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-PGF2alpha and that spironolactone can decrease urinary MCP-1 and oxidative stress.
Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50, Minami-Koshigaya, Koshigaya 343-8555, Japan. takeb@gmail.plala.or.jp
Kohzo
K
Takebayashi
Sachiko
S
Matsumoto
Yoshimasa
Y
Aso
Toshihiko
T
Inukai
D018932:Chemokine CCL2 / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D013148:Spironolactone / Q000627:therapeutic use*
D018932:Chemokine CCL2; D000451:Mineralocorticoid Receptor Antagonists; C075750:8-epi-prostaglandin F2alpha; D013148:Spironolactone; D015237:Dinoprost