Kidney disease affects about one out of three people with diabetes mellitus, a common medical
problem. Treatment of kidney disease with medications that lower blood pressure can slow the
kidney disease but there is no known cure. This study is designed to test the hypothesis
that certain combination-based blood pressure lowering regimens (of FDA approved medications)
are better than single agent-based regimens for lowering blood pressure and further slowing
or preventing progression of this incurable disease
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
