Improving Outcomes in Patients With Kidney Disease Due to Diabetes

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