Is enalaprilat (Angiotensin-Converting Enzyme (ACE) inhibitor) a safe option for a patient with severe hypertension, bradycardia, chronic kidney disease (CKD), and an allergy to hydralazine, who is currently on amlodipine (calcium channel blocker)?

Enalaprilat Use in Chronic Kidney Disease

Yes, enalaprilat (the active form of enalapril) remains a safe and appropriate option for severe hypertension in patients with chronic kidney disease, though dose adjustment is essential and close monitoring of renal function and potassium is mandatory. 1

Guideline-Based Recommendations for ACE Inhibitors in CKD

ACE inhibitors like enalaprilat are explicitly recommended as first-line therapy for hypertensive patients with CKD to achieve blood pressure targets of <130/80 mmHg and to slow kidney disease progression. 1

Key Supporting Evidence:

• The 2017 ACC/AHA guidelines give a Class IIa recommendation (Level B-NR evidence) for ACE inhibitor use in adults with hypertension and CKD stage 3 or higher, specifically to slow kidney disease progression 1

• The 2020 International Society of Hypertension guidelines state that RAS inhibitors (including ACE inhibitors) are first-line drugs in CKD because they reduce albuminuria in addition to BP control 1

• The 2024 ESC guidelines support combination therapy including RAS blockers for resistant hypertension, which appears relevant to this severe hypertension case 1

Critical Safety Considerations in CKD

Dose Adjustment is Mandatory:

In moderate to severe renal insufficiency, lower doses of enalapril achieve the same renoprotection and blood pressure control as higher doses, with better safety profiles. 2

• A randomized trial in patients with median GFR of 17 ml/min showed that low-dose enalapril (median 1.88 mg daily) provided equivalent renoprotection compared to high-dose (median 10 mg daily), with significantly less hyperkalaemia 2

• Patients on high-dose enalapril had a higher rate of progression to end-stage renal disease (5 patients vs. 0 patients, p=0.04) 2

Expected Initial GFR Decline:

An initial decline in GFR of approximately 14% (range -44% to +10%) is expected and clinically acceptable when starting enalapril in patients with severe chronic nephropathy. 3

• This initial decline does not indicate harm but rather reflects hemodynamic changes from reduced intraglomerular pressure 3

• Long-term studies show that despite this initial decline, ACE inhibitors slow the overall progression of renal insufficiency, particularly in diabetic nephropathy 4

Monitoring Requirements

Close monitoring of the following parameters is essential: 1

• Serum potassium: Expect increases of approximately 0.4-0.5 mmol/L; hyperkalaemia risk is dose-dependent 2, 4
• Serum creatinine and eGFR: Check within 1-2 weeks after initiation and after dose adjustments 1
• Blood pressure: Target <130/80 mmHg in CKD patients 1
• Proteinuria/albuminuria: ACE inhibitors typically reduce protein excretion 4, 5

Practical Dosing Algorithm for CKD

For patients with moderate to severe CKD (GFR <45 ml/min):

1. Start with low-dose enalaprilat (equivalent to enalapril 2.5 mg daily for GFR 10-25 ml/min, or 5 mg daily for GFR 25-45 ml/min) 5

2. Titrate based on blood pressure response, not to exceed doses that achieve adequate BP control 2

3. Add loop diuretics (not thiazides) if eGFR <30 ml/min for volume management 1

4. Continue amlodipine as it provides complementary renoprotection and cardiovascular benefits in CKD 6

Advantages Over Alternative Agents

Given the patient's hydralazine allergy and current amlodipine therapy, enalaprilat offers specific advantages:

• Hydralazine is contraindicated due to documented allergy 1

• Amlodipine alone may be insufficient for severe hypertension, though it provides renoprotection and is safe in CKD 1, 6

• ACE inhibitors provide unique renoprotective effects beyond blood pressure reduction, particularly important in CKD 1, 4

Common Pitfalls to Avoid

Do not discontinue enalaprilat if creatinine rises by <30% from baseline within the first 2 months, as this likely represents beneficial hemodynamic changes rather than acute kidney injury 3

Do not use high doses in advanced CKD; lower doses provide equivalent benefit with better safety 2

Do not combine with ARBs and aldosterone antagonists (triple RAS blockade), as this increases risk without additional benefit 1

Monitor potassium closely, especially if the patient develops bradycardia requiring beta-blocker discontinuation, as this removes one antihypertensive option 1