Emerging Strategies for Cardio-Renal Protection Beyond RAAS Blockade: Emphasis on Non-diabetic CKD and Resistant...

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Resistant hypertension in non-diabetic chronic kidney disease (ND-CKD) presents a significant cardiovascular and renal risk.
• Optimizing renin-angiotensin-aldosterone system inhibition (RAASi) alone may not be sufficient for cardio-renal protection in this high-risk group.

Purpose of the Study:

• To review contemporary evidence for cardio-renal protective strategies beyond traditional RAASi in ND-CKD.
• To emphasize mechanisms, clinical trial data, and practical sequencing of novel therapies.

Main Methods:

• Synthesis of current evidence from clinical trials and mechanistic studies.
• Focus on sodium-glucose cotransporter 2 inhibitors (SGLT2i), non-steroidal mineralocorticoid receptor antagonists (MRA), and GLP-1 receptor agonists.
• Consideration of potassium binders and device-based blood pressure management.

Main Results:

• SGLT2 inhibitors offer hemodynamic and tubular benefits, reducing renal and heart failure risk.
• Non-steroidal MRA (e.g., finerenone) target inflammation and fibrosis, potentially adding benefit with careful potassium monitoring.
• GLP-1 receptor agonists show cardiometabolic advantages and emerging renal benefits, especially in obese patients with high cardiovascular risk.

Conclusions:

• A stepwise implementation framework for novel therapies can maximize efficacy and minimize adverse events in ND-CKD with resistant hypertension.
• Structured monitoring and multidisciplinary care are crucial for managing these complex patients.
• Strategies beyond RAASi are essential for comprehensive cardio-renal protection.