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Effect of intensive blood pressure control on the course of type 1 diabetic nephropathy. Collaborative Study Group
1Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN 37232-2372, USA. julia.lewis@mcmail.vanderbilt.edu
Insights
Lowering mean arterial blood pressure (MAP) to 92 mm Hg or less in patients with type 1 diabetes and nephropathy on ACE inhibitors significantly reduces proteinuria. Intensive blood pressure control, combined with ACE inhibition, can lead to remission of diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Cardiology
Background:
- Diabetic nephropathy is a leading cause of end-stage renal disease in the US.
- Angiotensin-converting enzyme (ACE) inhibitors are a cornerstone therapy for diabetic nephropathy.
- Optimal blood pressure targets for renoprotection in this population remain under investigation.
Purpose of the Study:
- To assess the impact of different mean arterial blood pressure (MAP) control levels on type 1 diabetic nephropathy progression in patients on ACE inhibitor therapy.
- To examine the long-term course of diabetic nephropathy in a well-characterized cohort receiving ACE inhibitor therapy.
Main Methods:
- 129 patients with type 1 diabetes and nephropathy were randomized to a MAP goal of ≤92 mm Hg (group I) or 100-107 mm Hg (group II).
- Patients received ramipril as the primary antihypertensive agent and were followed for at least 2 years.
- Outcome measures included iothalamate clearance, creatinine clearance, and urinary protein excretion.
Main Results:
- No statistically significant difference in the rate of decline in renal function was observed between groups.
- A significant reduction in urinary protein excretion was found in the lower MAP group (535 mg/24 h) compared to the higher MAP group (1,723 mg/24 h; P = 0.02).
- 32% of patients achieved final urinary protein excretion <500 mg/24 h, with equivalent adverse event rates between groups.
Conclusions:
- A MAP goal of 92 mm Hg or less is recommended for optimal renoprotection in type 1 diabetic nephropathy, particularly when considering decreased proteinuria.
- Combining ACE inhibition with intensive blood pressure control can lead to regression or remission of clinical diabetic nephropathy.
- Lowering blood pressure to ≤92 mm Hg may be more effective in reducing proteinuria than higher targets in patients with type 1 diabetic nephropathy on ACE inhibitors.
Abstract:
Diabetic nephropathy is the most common cause of end-stage renal disease in the United States. We undertook a study to assess the impact of assignment to different levels of blood pressure control on the course of type 1 diabetic nephropathy in patients receiving angiotensin-converting enzyme (ACE) inhibitor therapy. We also examined the long-term course of this well-characterized cohort of patients receiving ACE inhibitor therapy. One hundred twenty-nine patients with type 1 diabetes and diabetic nephropathy who had previously participated in the Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy Study who had a serum creatinine level less than 4.0 mg/dL were randomly assigned to a mean arterial blood pressure (MAP) goal of 92 mm Hg or less (group I) or 100 to 107 mm Hg (group II). Patients received varying doses of ramipril as the primary therapeutic antihypertensive agent. All patients were followed for a minimum of 2 years. Outcome measures included iothalamate clearance, 24-hour creatinine clearance, creatinine clearance estimated by the Cockcroft and Gault formula, and urinary protein excretion. The average difference in MAP between groups was 6 mm Hg over the 24-month follow-up. The median iothalamate clearance in group I was 62 mL/min/1.73 m(2) at baseline and 54 mL/min/1.73 m(2) at the end of the study compared with a baseline of 64 mL/min/1.73 m(2) and final 58 mL/min/1.73 m(2) in group II. There were no statistically significant differences in the rate of decline in renal function between groups. There was a significant difference in follow-up total urinary protein excretion between group I (535 mg/24 h) and group II (1,723 mg/24 h; P = 0.02). Thirty-two percent of 126 patients achieved a final total protein excretion less than 500 mg/24 h. Patients from groups I and II had equivalent rates of adverse events. In patients with type 1 diabetes mellitus and diabetic nephropathy, the MAP goal should be 92 mm Hg or less for optimal renoprotection, if defined as including decreased proteinuria. With the combination of ACE inhibition and intensive blood pressure control, many patients can achieve regression or apparent remission of clinical evidence of diabetic nephropathy.