Is enalapril suitable for a patient with impaired renal function?

Enalapril Use in Severe Renal Impairment (Cr 1.68, GFR 42)

Enalapril can be used in this patient with moderate renal impairment, but requires dose reduction to 2.5 mg once daily as the starting dose, with careful monitoring for hyperkalemia and further renal function decline. 1

Dosing Recommendations Based on Renal Function

Your patient with creatinine 1.68 mg/dL and GFR 42 mL/min falls into the "mild impairment" category (CrCl >30 mL/min), where the standard 5 mg daily starting dose can be used according to FDA labeling. 1 However, given the borderline renal function, a more conservative approach starting at 2.5 mg daily would be prudent, particularly if the patient has heart failure or is volume-depleted. 1

Specific Dosing Algorithm by Renal Function:

• Normal renal function (CrCl >80 mL/min): Start 5 mg once daily 1
• Mild impairment (CrCl 30-80 mL/min): Start 5 mg once daily, but consider 2.5 mg if borderline or high-risk 1
• Moderate to severe impairment (CrCl ≤30 mL/min or serum creatinine ≥3 mg/dL): Start 2.5 mg once daily, maximum 40 mg daily 1
• Dialysis patients: 2.5 mg on dialysis days only, adjusted based on blood pressure response 1

Critical Safety Monitoring

The primary concerns with enalapril in renal impairment are hyperkalemia and acute worsening of renal function, not absolute contraindication. 1

Hyperkalemia Risk:

• Elevated serum potassium (>5.7 mEq/L) occurs in approximately 1% of hypertensive patients and 3.8% of heart failure patients 1
• Risk factors include renal insufficiency, diabetes, and concomitant use of potassium-sparing diuretics, potassium supplements, or salt substitutes 1
• Avoid combining enalapril with potassium supplements or potassium-sparing diuretics in patients with impaired renal function 1

Renal Function Monitoring:

• In patients with serum creatinine <1.9 mg/dL, enalapril can be safely administered with appropriate monitoring 2
• Renal function should be monitored during the first few weeks of therapy, as increases in blood urea nitrogen and serum creatinine may occur, particularly when combined with diuretics 1
• If renal function deteriorates, it typically occurs within the first 4 days and is reversible upon discontinuation 2

Evidence Supporting Use in Renal Impairment

The 2025 American Journal of Kidney Diseases guidelines emphasize that ACE inhibitors should not be routinely discontinued in patients with worsening kidney function, as withdrawal is associated with poorer clinical outcomes. 3 In heart failure patients with baseline creatinine of 1.6 mg/dL, continuing or reintroducing ACE inhibitors with adjunctive therapies (such as SGLT2 inhibitors) is preferred over permanent discontinuation. 3

Long-term Safety Data:

• A 3-year study of 153 patients with severe renal insufficiency showed enalapril was well-tolerated regardless of severity of renal impairment 4
• Low-dose enalapril (median 1.88 mg daily) provided equivalent renoprotection and blood pressure control compared to high-dose (median 10 mg daily) in patients with GFR 6-35 mL/min, with less hyperkalemia 5
• In patients with moderate to severe chronic nephropathy, enalapril reduced proteinuria without causing critical decline in renal function 6, 7

Clinical Context Considerations

When Enalapril is Particularly Indicated:

• Hypertension with diabetes, chronic kidney disease, or left ventricular dysfunction (LVEF <0.40) 3
• Heart failure (symptomatic or asymptomatic left ventricular dysfunction) 1
• Post-myocardial infarction with reduced ejection fraction 3

When to Exercise Extra Caution:

• Bilateral renal artery stenosis (increases in BUN and creatinine occur in 20% of patients, but are reversible) 1
• Volume depletion or concurrent high-dose diuretic therapy (risk of first-dose hypotension) 1
• Serum creatinine >1.9 mg/dL requires careful monitoring and prompt discontinuation if further deterioration occurs 2

Practical Management Strategy

1. Start with 2.5 mg once daily given the borderline renal function (Cr 1.68, GFR 42), even though FDA labeling permits 5 mg 1
2. Check serum potassium and creatinine within 1-2 weeks of initiation 1
3. Titrate dose upward as tolerated to achieve blood pressure control, up to maximum 40 mg daily 1
4. If creatinine rises >30% or potassium exceeds 5.5 mEq/L, consider dose reduction or adding SGLT2 inhibitor to mitigate hyperkalemia risk 3
5. Do not combine with potassium supplements or potassium-sparing diuretics 1

Common Pitfalls to Avoid

• Do not permanently discontinue enalapril for modest creatinine increases (10-20%) if blood pressure control is achieved and patient remains euvolemic 3
• Do not use enalapril within first 24 hours of acute MI due to risk of hypotension and renal dysfunction 3
• Do not switch between ACE inhibitors and other antihypertensives without considering that withdrawal is associated with worse outcomes 3
• Do not assume normal serum creatinine means normal renal function in elderly, women, or low body weight patients—always calculate creatinine clearance 8