Sequential RAAS blockade: is it worth the risk?

Area of Science:

• Nephrology
• Cardiovascular Pharmacology
• Renal Disease Research

Background:

• Renin-angiotensin-aldosterone system (RAAS) blockade is a primary treatment for chronic kidney disease (CKD).
• Despite RAAS monotherapy benefits, kidney prognosis in diabetic and nondiabetic CKD requires improvement.
• Combining RAAS blockers (dual blockade) has been explored to enhance renoprotection.

Purpose of the Study:

• To review the feasibility and advantages of dual RAAS blockade in renoprotective strategies.
• To critically evaluate the pros and cons of dual RAAS blockade based on existing evidence.
• To discuss the implications of recent hard endpoint trial results on dual RAAS blockade efficacy.

Main Methods:

• Review of findings from smaller studies, major endpoint trials, and meta-analyses on dual RAAS blockade.
• Analysis of short-term studies using surrogate endpoints like albuminuria.
• Evaluation of reported side effects, including hyperkalemia and hypotension.

Main Results:

• Initial studies showed promise for dual RAAS blockade, often using surrogate markers like albuminuria.
• Common side effects such as hyperkalemia and hypotension were observed but generally manageable.
• Recent large-scale trials with hard clinical endpoints have yielded disappointing results for dual RAAS blockade.

Conclusions:

• The clinical benefit of dual RAAS blockade for improving hard kidney outcomes is now questionable.
• The concept of dual RAAS blockade requires re-evaluation in light of recent trial outcomes.
• Further research is needed to determine the optimal role, if any, of combined RAAS blockade in CKD management.