Prospects for renovascular protection by more aggressive renin-angiotensin system control.

Risk factors such as hypertension or diabetes result in a continuum of renal damage. Without intervention, initial subclinical endothelial damage progresses to incipient disease, identified by microalbuminuria. Glomerular filtration rate declines, macroalbuminuria develops, and eventually end-stage renal disease (ESRD) emerges. Because of the interrelationship between cardiovascular and renal disease and their common pathophysiologies involving angiotensin II, many patients die of cardiovascular disease before renal replacement therapy is needed. Blood pressure control is key to renoprotection, but blood pressure-independent mechanisms are also implicated. Targeting the renin-angiotensin system (RAS) using angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) is a logical approach to managing all at-risk patients. In advanced nephropathy, therapy aims at retarding progression to ESRD. For incipient nephropathy, ideal therapy should bring about microalbuminuria regression. In patients at risk of renal damage, preventing early target-organ damage is essential. Although evidence of ACE inhibitor benefit is limited, data show that ARBs provide renoprotection throughout the continuum and that this may be related to their cardioprotective effects. More aggressive RAS targeting by combination blockade is under investigation. Telmisartan is an ARB that delays progression of incipient and overt diabetic nephropathy and brings about regression from microalbuminuria to normoalbuminuria in hypertensive and normotensive patients. The ultimate proof of benefit will come from the ONTARGET trial, which will evaluate the cardiovascular and renal protective effects of the combination of telmisartan and ramipril.