From the Guidelines
Entresto (sacubitril/valsartan) can be used cautiously in patients with elevated BUN and creatinine, but requires close monitoring, as evidenced by the European Society of Cardiology guidelines 1.
Key Considerations
- For patients with mild to moderate renal impairment (eGFR ≥30 mL/min/1.73m²), no dose adjustment is typically needed.
- For severe renal impairment (eGFR <30 mL/min/1.73m²), a lower starting dose of 24/26 mg twice daily is recommended with careful titration.
- Entresto should be avoided in patients with end-stage renal disease (eGFR <15 mL/min/1.73m²) due to limited clinical experience.
Monitoring and Dose Adjustment
- Monitor kidney function and potassium levels closely, especially during the first few weeks of treatment.
- Temporary dose reduction or interruption may be necessary if significant worsening of renal function occurs.
- The medication works through dual inhibition of neprilysin and the renin-angiotensin-aldosterone system, which can affect renal hemodynamics.
Renal Protective Effects
- While Entresto has shown overall renal protective effects in heart failure patients compared to ACE inhibitors, individual responses vary, particularly in those with pre-existing kidney dysfunction, as noted in studies 1.
Clinical Guidance
- Check renal function and electrolytes before initiating Entresto, and re-check blood chemistry 1–2 weeks after initiation and after any increase in dose 1.
- A specialist HF nurse may assist with education of the patient, follow-up, biochemical monitoring, and dose adjustment 1.
From the FDA Drug Label
5.4 Impaired Renal Function As a consequence of inhibiting the renin-angiotensin-aldosterone system (RAAS), decreases in renal function may be anticipated in susceptible individuals treated with sacubitril and valsartan [see Adverse Reactions (6.1)]. In patients whose renal function depends upon the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria, progressive azotemia and, rarely, acute renal failure and death Closely monitor serum creatinine, and down-titrate or interrupt sacubitril and valsartan in patients who develop a clinically significant decrease in renal function [see Use in Specific Populations (8.7) and Clinical Pharmacology (12. 3)]. As with all drugs that affect the RAAS, sacubitril and valsartan may increase blood urea and serum creatinine levels in patients with bilateral or unilateral renal artery stenosis. In patients with renal artery stenosis, monitor renal function.
Entresto (sacubitril and valsartan) may worsen renal function, especially in patients with pre-existing renal impairment.
- Key considerations:
- Closely monitor serum creatinine in patients with elevated BUN and creatinine.
- Down-titrate or interrupt sacubitril and valsartan if a clinically significant decrease in renal function occurs.
- Use with caution in patients with renal artery stenosis, as sacubitril and valsartan may increase blood urea and serum creatinine levels. 2
From the Research
Entresto and Renal Function
- Entresto, also known as sacubitril/valsartan, is a medication used to treat heart failure with reduced ejection fraction (HFrEF) 3.
- Elevated blood urea nitrogen (BUN) and creatinine levels are indicators of renal impairment, which can be a concern in patients with heart failure 4.
- A study found that sacubitril/valsartan was effective in patients with HFrEF, including those with advanced renal impairment, and was associated with improved outcomes compared to standard heart failure treatment without ARNI 5.
Effects of Sacubitril/Valsartan on Renal Function
- A meta-analysis found that sacubitril/valsartan increased estimated glomerular filtration rate (eGFR) in patients with heart failure and chronic kidney disease (CKD) compared to renin-angiotensin system (RAS) inhibitors 6.
- However, sacubitril/valsartan had no significant effect on urinary albumin/creatinine ratio (UACR) compared to the control group 6.
- Another study found that sacubitril/valsartan was associated with decreased systolic blood pressure, diastolic blood pressure, and N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels in patients with heart failure and CKD 6.
Factors Associated with Sacubitril/Valsartan Continuation
- A study found that factors associated with sacubitril/valsartan continuation included albumin ≥ 3.5 g/dL, body mass index (BMI) ≥ 18.5 kg/m2, and systolic blood pressure (SBP) ≥ 110 mmHg 7.
- The study also found that initiating only sacubitril/valsartan without simultaneously initiating other heart failure medications in patients with HFrEF may lead to sacubitril/valsartan continuation 7.