Improving Outcomes in Patients With Kidney Disease Due to Diabetes

Launched by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES (NIDDK) · Sep 26, 2006

Keywords

ClinConnect Summary

The long-range objective of this project is to prevent progression of diabetic nephropathy, the leading cause of end-stage renal disease (ESRD). In most patients diabetic nephropathy progresses inexorably to ESRD despite inhibition of the renin-angiotensin- aldosterone system with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs). The specific aims of this proposal are to: 1) recruit a multiethnic cohort of 78 young adults (ages 20-40) with type 1 (n=36) or type 2 (n=36) diabetes and overt nephropathy (defined as a urine albumin/creatinine ra...

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Eligibility criteria

• 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