An open label multi facilities cooperation randomized control trial to verify renoprotective effects of pioglitazone therapy in diabetic nephropathy

INTERVENTION: This study is a prospective randomized control trial. The entry period of this study is one year. Subjects were type 2 diabetics with nephropathy, taking RAS inhibitors. The patients were randomly assigned to two groups, a pioglitazone group (7.5 mg/day or 15 mg/day) and other hypoglycemic agents group. Pioglitazone can be properly increased to 30mg/day when the anti‐hyperglycemic effect is insufficient. Blood pressure, body weight, hemoglobin A1c (HbA1c), serum creatine, serum lipids, the plasma and urinary levels of monocyte chemoattractant protein (MCP)‐1, interleukin‐6 (IL‐6) and, urinary albumin excretion (albumin to creatinine ratio: ACR) and urinary excretions of 8‐hydroxydeoxyguanosine (8‐OHdG) were determined before (baseline levels) and after the treatment for 6 months , 12 months and 24 months.. We collected fasting blood and first urine samples in early morning. CONDITION: Type 2 diabetic nephropathy patients with chronic kidney disease (CKD) PRIMARY OUTCOME: Estimated GFR decrease in 50% or more, increase of serum creatinine level to 3mg/dl or more, changes of urinary albumin excretion SECONDARY OUTCOME: Cardiovascular event: Appearance of disease of total death, nonfatal myocardial infarction (The asymptomatic cardiac infarction is included), and apoplexy, cerebral infarction, cardiac failure (BNP>1000pg/ml), and the serious illness edema INCLUSION CRITERIA: The subjects enrolled in the present study were type 2 diabetic out‐patients with nephropathy, who visit our hospitals and fulfilled the following criteria:1) Mild or moderate hyperglycemia, defined as the HbA1c of 6.0‐7.9 %. 2) Use of RAS inhibitors, such as an angiotensin‐converting enzyme inhibitor (ACEI) or an angiotensin II type‐1 receptor blocker (ARB), for at least six months. 3) A urinary albumin‐to‐creatinine ratio (ACR) higher than 30 (mg/mgCr) (stage of diabetic nephropathy: stage II and higher).4) Not severe hypertension (blood pressure < 160/110 mmHg)