What are the recommended medications for hypertension (HTN) in patients with impaired renal function?

Recommended Medications for Hypertension in Renal Failure

ACE inhibitors or ARBs are the first-line antihypertensive agents for patients with renal failure, particularly when albuminuria is present, as they provide both blood pressure control and direct renoprotection beyond their BP-lowering effects. 1

First-Line Therapy: RAS Inhibitors

• ACE inhibitors or ARBs should be initiated as first-line therapy in patients with CKD and severely increased albuminuria, with strong evidence supporting their use regardless of diabetes status 1
• These agents reduce proteinuria and slow progression of renal dysfunction through mechanisms beyond simple BP reduction, including decreased intraglomerular pressure 2
• For patients with CKD but no albuminuria, RAS inhibitors remain a reasonable treatment option 1

Critical Monitoring Requirements

• Check serum creatinine and potassium within 2-4 weeks of initiating or increasing RAS inhibitor doses 1
• Continue therapy unless creatinine rises >30% within 4 weeks of initiation or dose increase 1
• Consider dose reduction or discontinuation only for symptomatic hypotension, uncontrolled hyperkalemia despite treatment, or advanced kidney failure (eGFR <15 mL/min/1.73 m²) 1

Important Contraindications

• Never combine ACE inhibitors, ARBs, and direct renin inhibitors in patients with CKD due to increased adverse events, particularly in those with renal insufficiency or diabetes 3, 1
• RAS inhibitors are absolutely contraindicated in pregnancy 1
• Use with caution in peripheral vascular disease due to association with renovascular disease 3, 1

Second-Line and Add-On Therapy

Diuretics for Volume Control

• In severe renal impairment (eGFR <30 mL/min), loop diuretics should replace thiazide diuretics for volume control, though they are less effective for BP lowering 3
• Thiazide or thiazide-like diuretics (chlorthalidone or indapamide) maintain efficacy down to eGFR of 30 mL/min/1.73 m² and should be used in combination with RAS inhibitors 3
• Diuretics must be used together with an ACE inhibitor or ARB and a β-blocker for optimal outcomes 3

Calcium Channel Blockers

• Dihydropyridine CCBs (amlodipine, felodipine) are safe and effective add-on agents when additional BP lowering is needed beyond RAS inhibitor therapy 1, 4
• For kidney transplant recipients specifically, a dihydropyridine CCB or ARB is recommended as first-line therapy 1
• Amlodipine does not adversely affect renal function and may be used at standard doses (5-10 mg daily) without dose adjustment in renal impairment 4, 5, 6
• Avoid non-dihydropyridine CCBs (verapamil, diltiazem) due to negative inotropic effects and potential to worsen heart failure 3

Mineralocorticoid Receptor Antagonists

• Spironolactone or eplerenone are highly effective for resistant hypertension but require careful monitoring 3, 1
• Do not use if serum creatinine ≥2.5 mg/dL (men) or ≥2.0 mg/dL (women), or if potassium ≥5.0 mEq/L 3
• When used with eGFR <30 mL/min/1.73 m², there is significant risk of hyperkalemia and reversible decline in kidney function requiring close monitoring 1
• Hyperkalemia can often be managed with potassium-lowering measures rather than stopping the RAS inhibitor 1

Blood Pressure Targets

• Target systolic BP <120 mmHg when tolerated in adults with CKD 1
• For patients with moderate-to-severe CKD (eGFR >30 mL/min/1.73 m²), aim for systolic BP 120-129 mmHg if tolerated 1
• Alternative target of 130-139 mmHg systolic is acceptable in diabetic or non-diabetic CKD 1

Treatment Algorithm for Renal Failure

1. Start with ACE inhibitor or ARB (particularly if albuminuria present) 1
2. Add dihydropyridine CCB or thiazide/thiazide-like diuretic if additional BP lowering needed 1
   • Use loop diuretic instead if eGFR <30 mL/min 3
3. Consider mineralocorticoid receptor antagonist for resistant hypertension with close potassium/renal monitoring 3, 1
4. For Black patients: Consider starting with CCB or diuretic, then add RAS inhibitor as needed 1

Special Populations

Beta-Blockers

• Carvedilol, metoprolol succinate, bisoprolol, or nebivolol are preferred if heart failure with reduced ejection fraction coexists 3
• Atenolol requires dose reduction: 50% dose if CrCl 15-35 mL/min, 25% dose if CrCl <15 mL/min 3

Drugs to Avoid

• α-blockers (doxazosin) should only be used if other agents at maximum doses fail to control BP 3
• Clonidine and moxonidine should be avoided due to increased mortality risk in similar patient populations 3
• NSAIDs should be used with extreme caution due to effects on BP, volume status, and worsening renal function 3

Common Pitfalls

• Failing to monitor creatinine and potassium within 2-4 weeks of RAS inhibitor initiation is a critical error that can lead to dangerous hyperkalemia 1
• Prematurely discontinuing RAS inhibitors for modest creatinine elevations (<30% increase) deprives patients of renoprotective benefits 1
• Using thiazide diuretics when eGFR <30 mL/min results in ineffective therapy; switch to loop diuretics 3
• Combining multiple RAS inhibitors increases adverse events without additional benefit 3, 1