## Clinical Context This patient has stage 1 hypertension with early chronic kidney disease (eGFR 65) and microalbuminuria (UACR 45 mg/g), indicating glomerular hyperfiltration and incipient diabetic-like renal injury. He requires an agent that: 1. Reduces intraglomerular pressure 2. Provides cardio-renal protection 3. Slows CKD progression 4. Reduces cardiovascular risk ## Why ACE Inhibitor (Lisinopril) is Correct **Key Point:** ACE inhibitors are the first-line add-on agent in hypertensive patients with CKD and albuminuria, regardless of diabetes status. **High-Yield:** ACE inhibitors: - Dilate efferent arterioles → reduce glomerular capillary pressure - Reduce proteinuria/albuminuria by 30–50% - Slow eGFR decline in CKD - Reduce cardiovascular events in high-risk patients - Are renoprotective even in non-diabetic CKD **Clinical Pearl:** The combination of a calcium channel blocker (amlodipine) + ACE inhibitor (lisinopril) is synergistic: CCB causes reflex tachycardia and mild sodium retention, which ACE-I counteracts. This is a guideline-recommended dual therapy for CKD. **Mechanism:** ACE inhibitors block angiotensin II formation, reducing vasoconstriction of efferent arterioles and decreasing intraglomerular pressure. They also reduce TGF-β-mediated fibrosis. ## Evidence Base | Feature | ACE Inhibitor | ARB | Thiazide | Beta-blocker | |---------|---------------|-----|----------|---------------| | Reduces albuminuria | ✓✓✓ | ✓✓✓ | ✗ | ✗ | | Slows CKD progression | ✓✓✓ | ✓✓✓ | ✗ | ✗ | | Reduces CV events in CKD | ✓✓✓ | ✓✓ | ✓ | ✓ | | Cardio-renal protection | ✓✓✓ | ✓✓✓ | ✗ | ✗ | | First-line in CKD + albuminuria | ✓ | ✓ (if ACE-I intolerant) | ✗ | ✗ | [cite:Harrison 21e Ch 297]
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