The reno-protective effect of the dual blockade of the renin angiotensin system (RAS)

Abstract

Hypertension and proteinuria are risk factors for renal disease progression. There is clear evidence that pharmacological blockade of the RAS with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) reduces proteinuria and slows down the progression of renal disease in diabetic and non diabetic nephropathies, a beneficial effect not related to blood pressure control. However, not all patients respond similarly to these treatments. Some patients exhibit a significant beneficial response while others do not. The absence of response may be explained by the incomplete blockade of the RAS obtained with ACEI, which are unable to block completely the formation of AII, some generation of AII is produced via other non ACE pathways. In the search of new alternatives that could improve the antiproteinuric and nephroprotective effects of RAS blockers, the association of ACEI and ARB might prove to be useful. ARB produces a complete blockade of the RAS and stimulates the vasodilating and non-proliferative actions of AII via the AT-2 receptor. Furthermore, ACE inhibitors but not ARB; inhibit the metabolism of kinins, which increases the level of bradykinin, a potent vasodilator. Recently, several authors have shown a more marked antiproteinuric effect of the dual blockade of the RAS versus ACEI or ARB alone in spite of a similar effect on blood pressure. A recent study also has demonstrated that this more marked antiproteinuric effect is associated with a less progression of renal disease in primary, non diabetic nephropathies. Furthermore, at least two studies have shown that, treatment with ARB postpones end-stage renal disease and reduces the rate of decline in renal function in patients with type 2 diabetes and nephropathy, but until now, there is not any clear evidence of a superior beneficial effect of dual blockade versus maximal recommended dose of ARB regarding renal progression in type 2 diabetic nephropathy, which is the most frequent cause of end stage renal disease. Long-term clinical trials are needed and encouraged to further establish the significant role of dual blockade in renal protection particularly in diabetic nephropathy.