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

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Hypertension and diabetes are key risk factors for progressive renal damage, leading from subclinical endothelial dysfunction to end-stage renal disease (ESRD).
• Cardiovascular disease (CVD) and renal disease share common pathophysiologies involving angiotensin II, often resulting in patient mortality before renal replacement therapy is required.
• Blood pressure control is crucial for renoprotection, but blood pressure-independent mechanisms also play a significant role.

Purpose of the Study:

• To evaluate the role of renin-angiotensin system (RAS) targeting, specifically angiotensin receptor blockers (ARBs), in managing renal damage across its continuum.
• To assess the renoprotective and cardioprotective effects of ARBs, including telmisartan, in patients with incipient and overt nephropathy.
• To investigate the potential benefits of combination RAS blockade, such as telmisartan with ramipril, in delaying renal disease progression and preventing target-organ damage.

Main Methods:

• Review of existing data on ARBs and angiotensin-converting enzyme (ACE) inhibitors in managing renal disease.
• Analysis of telmisartan's effects on delaying diabetic nephropathy progression and promoting microalbuminuria regression.
• Consideration of ongoing trials, such as ONTARGET, evaluating combination RAS blockade.

Main Results:

• ARBs demonstrate renoprotection throughout the renal damage continuum, potentially due to cardioprotective effects.
• Telmisartan has shown efficacy in delaying diabetic nephropathy progression and achieving regression from microalbuminuria to normoalbuminuria in hypertensive and normotensive individuals.
• Evidence for ACE inhibitor benefit in renoprotection is limited compared to ARBs.

Conclusions:

• Targeting the RAS with ARBs is a logical and effective strategy for managing patients at risk of renal damage.
• ARBs provide significant renoprotection and may offer cardioprotective benefits, making them valuable across the spectrum of kidney disease.
• Combination RAS blockade warrants further investigation for enhanced cardiovascular and renal outcomes, as exemplified by the ONTARGET trial.