Improving Outcomes in Patients With Kidney Disease Due to Diabetes

This is an interventional treatment trial for Diabetes focused on measuring double-blind, placebo-controlled, nephropathy, blood pressure, urine albumin to creatinine ratio, placebo Read More

Inclusion Criteria:

• Adult male and female subjects aged 20-65 of all ethnic backgrounds.
• Type I diabetes mellitus defined as sudden onset of insulin requiring diabetes prior to age 20 and at least 5 years duration
• Type 2 diabetes mellitus defined as onset > 20 years of age and treatment with oral hypoglycemic agent and/or insulin and increased C-peptide level.
• Seated SBP > 130 mmHg documented at one screening visit or treated SBP < 130 mmHg with a documented history of SBP > 130 mmHg on more than one previous occasion
• Proteinuria defined as a 24-hour urine albumin/creatinine ratio > 300 mg/g while on an ACE inhibitor with or without non-ARB, non-aldosterone antagonist treatment
• Ongoing treatment (> 3 months) with an ACE inhibitor or ARB with or without additional antihypertensive therapy (e.g. CCB, a-blocker, b-blocker, clonidine).

Exclusion Criteria:

• BMI > 45 kg/m2
• Baseline serum creatinine > 3.0 mg/dl in females and > 4.0 mg/dl in males or creatinine clearance <20 ml/min estimated by Cockcroft-Gault equation (based on age, fasting serum creatinine concentration and ideal body weight in kilograms).
• Secondary cause of kidney disease other than diabetic nephropathy
• Serum potassium concentration >5.5 mEq/L on ACE inhibitor therapy 7-10 days prior to randomization
• Poorly controlled diabetes, i.e. HgbA1C > 11 mg/dl 7-10 days prior to randomization
• History of allergy to iothalamate or history of renal failure due to contrast nephropathy
• Stroke or myocardial infarction within the preceding 12 months prior to randomization
• Coronary revascularization procedure within past 6 months
• Clinically apparent congestive heart failure defined as clinical signs of heart failure or an ejection fraction of < 40% (and/or depressed LV systolic function by echocardiogram).
• Terminal disease including cancer and AIDS
• Documented increase in serum creatinine > 50% of baseline within 3 months prior to the run-in period
• Renal disease known or in the opinion of the investigator caused by a condition other than diabetes
• Known adverse reaction to study medications including ACE inhibitors, ARB and spironolactone
• History of chronic or intermittent gross hematuria
• Spontaneous 24-hour urine sodium excretion rate exceeding 350 mEq/day
• AST or ALT greater than 2.5 the upper limit of normal for the laboratory
• Pregnancy
• History of autoimmune disease, connective tissue disease or multiple drug allergies
• Anticipated need for renal replacement therapy within 12 months Inclusion criteria for normal subjects
• Adult male and female subjects aged 20-65 of all ethnic backgrounds Exclusion criteria for normal subjects
• Chronic medical conditions, including but not limited to diabetes mellitus, hypertension, chronic kidney disease, and hyperlipidemia.
• Use of medications for antihypertensive
• Inability to follow study protocol for any reason