Treatment of diabetic nephropathy with angiotensin II blockers

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.