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Combination antihypertensive therapy in the treatment of diabetic nephropathy
Geoffrey Boner1, Zemin Cao, Mark E Cooper
1Institute of Hypertension and Kidney Diseases, Rabin Medical Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. gboner@clalit.org.il
Insights
Diabetic nephropathy management often requires multiple medications. Combining angiotensin converting enzyme inhibitors (ACE-I) with angiotensin II receptor blockers (AIIR) may offer benefits for patients with persistent hypertension or proteinuria.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetic nephropathy is a leading cause of end-stage renal disease.
- It frequently co-occurs with macrovascular complications like ischemic heart disease.
- Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (AIIR) are first-line treatments for hypertension and renal protection in diabetes.
Purpose of the Study:
- To evaluate the role of combination therapy in managing diabetic nephropathy.
- To explore the potential synergistic effects of combining different antihypertensive agents.
Main Methods:
- Review of existing studies on combination therapies for diabetic nephropathy.
- Analysis of data from animal models and human trials involving ACE-I, AIIR, and calcium channel blockers.
Main Results:
- ACE-I and AIIR are crucial for managing diabetic nephropathy.
- Combination therapy, including calcium channel blockers with ACE-I, has shown some synergistic effects on proteinuria, though not consistently substantiated.
- Studies on combining ACE-I with AIIR show mixed results regarding synergistic effects on proteinuria and hypertension.
Conclusions:
- Target blood pressure levels for diabetics with proteinuria are defined (e.g., 130/80 mm Hg or 125/75 mm Hg).
- Calcium channel blockers are important for blood pressure control in diabetic nephropathy.
- The combination of ACE-I and AIIR may be considered for patients unresponsive to monotherapy or other combinations, pending further evidence.
Abstract:
Diabetic nephropathy is one of the major causes of end-stage renal disease and is often associated with other macrovascular complications such as ischemic heart disease and peripheral vascular disease. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (AIIR) have both been shown to have a protective effect on the progression of diabetic nephropathy and have thus become the first choice for treatment of hypertension and/or renal involvement in patients with diabetes. However, most of these patients, especially those with type 2 diabetes, require two of more medications in order to reduce their blood pressure to the levels, which have been proposed in recently published consensus papers. These target blood pressure levels are 130/80 mm Hg in diabetic subjects with proteinuria of up to 1 g/day and 125/75 mm Hg in those with proteinuria in excess of 1 g/day. Combinations of different medications may have a synergistic effect. Some of the early studies using a combination of either a nondihydropyridine or a dihydropyridine calcium channel blocker with ACE-I demonstrated a synergistic effect on proteinuria in patients with diabetic nephropathy. However, these studies have not been substantiated, but calcium channel blockers, with their proven ability to reduce blood pressure, play an important role in the treatment of patients with diabetic nephropathy and hypertension. The combination of ACE-I with AIIR may have several theoretical advantages. Many studies using this combination have been performed in animal models of diabetes and in patients with diabetic and nondiabetic renal disease. Some of these studies have demonstrated a synergistic effect of the combination on proteinuria or hypertension, but the results have not been consistent in all studies. It may be concluded that, until additional studies provide more convincing evidence, this combination could be used in patients whose proteinuria or hypertension has not responded to either one of the agents as monotherapy or to a combination of other medications.