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Treatment of diabetic nephropathy with angiotensin II blockers
1First Department of Medicine, Faculty of Medicine, Szeged University, Szeged, Hungary. sons@in1st.szote.u-szote.u-szeged.hu
Abstract:
The increased activity of the renin-angiotensin-aldosterone system (RAAS) is an important pathogenetic factor in the development of nephropathy in diabetic patients. The damaging factor of this system is the end-product, angiotensin II, and the damaging effects are vasoconstriction, increase of aldosterone secretion, growth, fibrosis, thrombosis, inflammation and oxidation. Theoretically, on this basis, blockade of the RAAS should have a beneficial effect on the development of diabetic nephropathy. The main goal in the treatment of diabetic nephropathy is control of the glycaemic status and aggressive antihypertensive therapy, primarily with RAAS-blocking agents. It was demonstrated recently that angiotensin II receptor blockers (ARBs) have a slowing effect on the progression of diabetic nephropathy (RENAAL and IDNT trials) or on the development of proteinuria (IRMA) in type 2 diabetes. These effects are specific and independent of the decrease in blood pressure. Theoretically, the combination of an angiotensin-converting enzyme inhibitor (ACEI) and an ARB can lead to a more complete blockade of the RAAS. A new study (ONTARGET) has now started to investigate whether treatment with a combination of an ACEI and an ARB has a more potent beneficial effect on the cardiovascular events and the nephropathy in type 2 diabetic patients as compared with separate treatment with the two agents.
Insights
Diabetic nephropathy is linked to the renin-angiotensin-aldosterone system (RAAS). Blocking this system may protect kidneys, and a new study explores combining ACE inhibitors and ARBs for better results.
Area of Science:
- Nephrology
- Endocrinology
- Cardiovascular Medicine
Background:
- The renin-angiotensin-aldosterone system (RAAS) plays a key role in diabetic nephropathy.
- Angiotensin II, a product of RAAS, causes vasoconstriction, inflammation, and fibrosis, damaging kidneys.
Purpose of the Study:
- To investigate the potential benefits of blocking the RAAS in diabetic nephropathy.
- To evaluate if combining an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) offers superior protection against cardiovascular events and nephropathy in type 2 diabetes compared to monotherapy.
Main Methods:
- Review of existing studies demonstrating the efficacy of ARBs in slowing diabetic nephropathy progression and reducing proteinuria.
- Initiation of the ONTARGET study to compare combination therapy (ACEI + ARB) with monotherapy in type 2 diabetic patients.
Main Results:
- Angiotensin II receptor blockers (ARBs) have shown a specific, blood pressure-independent effect in slowing diabetic nephropathy progression and reducing proteinuria in type 2 diabetes.
- The ONTARGET study is designed to assess the enhanced efficacy of dual RAAS blockade.
Conclusions:
- Blockade of the RAAS is a theoretically sound strategy for managing diabetic nephropathy.
- Further investigation through trials like ONTARGET is crucial to determine the optimal RAAS-blocking strategy, particularly the combination of ACE inhibitors and ARBs, for comprehensive patient benefit.