Effect of Entresto (Sacubitril/Valsartan) on Kidney Function
Entresto (sacubitril/valsartan) can affect kidney function, potentially causing temporary decreases in estimated glomerular filtration rate (eGFR), but it generally has a renoprotective effect over time compared to other treatments, especially in patients with heart failure.
Mechanism of Action and Kidney Effects
Entresto affects kidney function through its dual mechanism:
Valsartan component: As an angiotensin receptor blocker (ARB), it inhibits the renin-angiotensin-aldosterone system (RAAS), which can cause:
- Initial decrease in eGFR due to reduced efferent arteriolar tone
- Potential for hyperkalemia
- Possible acute kidney injury in susceptible patients
Sacubitril component: As a neprilysin inhibitor, it increases natriuretic peptides which:
- Promotes natriuresis and diuresis
- May provide additional renoprotective effects
Initial Effects on Kidney Function
When starting Entresto, patients may experience:
- Temporary decrease in eGFR: This is expected and similar to what occurs with ACE inhibitors or ARBs 1
- Initial rise in serum creatinine: This is often transient and not necessarily indicative of kidney damage
- Risk of acute kidney injury: Particularly in susceptible populations 1
Long-Term Renal Effects
Recent research demonstrates that Entresto may have beneficial effects on kidney function over time:
- In patients with heart failure with preserved ejection fraction (HFpEF), Entresto slows the decline in eGFR compared to valsartan alone 2
- In patients with chronic kidney disease (CKD) and HFpEF, Entresto more effectively slows down renal function decline than ACE inhibitors/ARBs 3
- In the PARAGON-HF trial, sacubitril/valsartan attenuated decline in eGFR in patients both with and without diabetes 2
Special Populations and Considerations
Patients with Renal Impairment
- Moderate renal impairment (eGFR 30-60 mL/min/1.73m²): No dose adjustment needed when starting Entresto 4
- Severe renal impairment (eGFR <30 mL/min/1.73m²): Starting dose should be reduced to 24/26 mg twice daily 4
- Monitoring: Renal function and potassium should be assessed within 1-2 weeks after initiation or dose increase 4
Risk Factors for Renal Dysfunction
Entresto may cause more significant renal impairment in patients with:
- Bilateral renal artery stenosis or stenosis of a dominant/single kidney
- Volume depletion or dehydration
- Concomitant use of nephrotoxic drugs (NSAIDs, etc.)
- Pre-existing severe renal impairment 1
Monitoring Recommendations
- Baseline assessment: Measure serum creatinine, eGFR, and potassium before starting therapy
- Follow-up monitoring: Check renal function and electrolytes within 1-2 weeks after initiation or dose changes 4
- Ongoing monitoring: Regular assessment based on clinical stability but at least monthly for the first 3 months and every 3 months thereafter 4
Management of Renal Dysfunction
If renal function worsens:
- A decrease in eGFR of >30% should alert clinicians that dose reduction may be necessary 4
- In patients with evidence of hypovolemia, reduce diuretic doses
- Entresto dose may need to be reduced in setting of renal insufficiency or hypotension
- Temporary discontinuation may be necessary in severe cases 1
Conclusion
While Entresto can cause initial decreases in kidney function similar to other RAAS inhibitors, recent evidence suggests it may have long-term renoprotective effects compared to ARBs alone. The most recent research from the PARAGON-HF trial 2 demonstrates that Entresto attenuates the decline of eGFR and reduces clinically relevant kidney events in patients with heart failure.
Careful monitoring of renal function is essential, particularly when initiating therapy and in patients with pre-existing renal impairment or other risk factors for kidney dysfunction.