How should renal function be monitored in patients taking Entresto (sacubitril/valsartan) with impaired renal function?

Renal Function Monitoring for Entresto (Sacubitril/Valsartan)

Monitor serum creatinine and potassium within 1-2 weeks after initiating or increasing the dose of Entresto, then continue monitoring at least every 3 months during stable maintenance therapy, with more frequent assessment in patients with baseline renal impairment. 1, 2

Initial Monitoring Strategy

• Check baseline renal function (serum creatinine, eGFR) and potassium before starting Entresto. 3
• Recheck serum creatinine and potassium 1-2 weeks after initiation or any dose increase. 1, 2
• For patients with moderate renal impairment (eGFR 30-60 mL/min/1.73 m²), no dose adjustment is needed at initiation, but monitor more closely. 1
• For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), start with a reduced dose of 24/26 mg twice daily. 1

Ongoing Maintenance Monitoring

• Monitor renal function and potassium every 3 months once the patient is on a stable dose. 1, 2
• In patients with pre-existing renal impairment, consider more frequent monitoring by dividing the CrCl by 10 to determine the minimum interval in months (e.g., CrCl 40 mL/min = monitor every 4 months). 1
• Monitor more frequently in elderly patients, those with diabetes, or patients on multiple nephrotoxic medications. 2

Interpreting Changes in Renal Function

Acceptable changes:

• Up to 30% increase in creatinine or 25% decrease in eGFR is acceptable after starting Entresto. 1, 2
• An initial mild worsening of renal function may occur before longer-term renal function preservation, similar to other RAAS inhibitors. 1

Action thresholds requiring intervention:

• If eGFR decreases by >30% or creatinine increases by >30%, consider dose reduction or temporary discontinuation. 1, 3
• Closely monitor serum creatinine and down-titrate or interrupt Entresto in patients who develop a clinically significant decrease in renal function. 3
• If hypovolemia is present, reduce diuretic doses first before adjusting Entresto. 3

Potassium Management

• Monitor potassium periodically, especially in patients with severe renal impairment, diabetes, or those on a high-potassium diet. 3
• Avoid initiating Entresto if baseline potassium is >5.0 mEq/L. 1
• If potassium rises to 5.5-5.9 mmol/L, consider dose reduction and dietary counseling. 2
• If potassium reaches ≥6.0 mmol/L, discontinue Entresto temporarily and address underlying causes. 1, 2
• Consider newer potassium binders (patiromer, sodium zirconium cyclosilicate) in patients with persistent hyperkalemia, though their impact on outcomes in heart failure is not yet established. 1

Special Considerations for Renal Impairment

Pharmacokinetic effects:

• Sacubitrilat (the active neprilysin inhibitor) exposure increases 2.1-fold in mild, 2.2-fold in moderate, and 2.7-fold in severe renal impairment, while sacubitril and valsartan exposure remains unchanged. 4
• The half-life of sacubitrilat increases from 12 hours in normal renal function to 21-39 hours in renal impairment. 4

Clinical outcomes in renal dysfunction:

• In patients with eGFR 30-60 mL/min/1.73 m², Entresto actually improves eGFR over time (mean increase of 4.1 mL/min/1.73 m² at 10 weeks). 5
• Patients with renal dysfunction experience higher rates of hyperkalemia (16.3% vs 6.5% without renal dysfunction) and investigator-reported renal impairment (6.4% vs 2.1%). 5
• Despite these risks, most patients with renal dysfunction tolerate Entresto and show significant improvements in renal function and cardiac biomarkers. 5

High-Risk Populations Requiring Intensive Monitoring

• Patients with baseline eGFR <60 mL/min/1.73 m² should have renal function checked within 1-2 weeks of initiation, then monthly for the first 3 months, then every 3 months thereafter. 1, 2
• Elderly patients require closer monitoring due to age-related decline in renal function. 2
• Patients on concurrent diuretics, especially high doses, need more frequent assessment due to volume depletion risk. 1, 3
• Patients with bilateral renal artery stenosis require close monitoring as Entresto may worsen renal function in this population. 3

Common Pitfalls to Avoid

• Do not discontinue Entresto for mild, transient increases in creatinine (<30% rise), as initial hemodynamic changes are expected and do not predict long-term adverse outcomes. 1
• Do not confuse acute kidney injury with chronic kidney disease—in acute settings, calculated CrCl may underestimate the severity of renal impairment. 1
• Do not overlook volume status—correct hypovolemia with diuretic adjustment before attributing renal dysfunction solely to Entresto. 3
• Do not use Entresto in patients with severe renal impairment without dose reduction (start at 24/26 mg twice daily). 1