ARNI Use in Patients with eGFR Less Than 10
ARNI (Angiotensin Receptor-Neprilysin Inhibitor) is not recommended for patients with an eGFR less than 10 mL/min/1.73m² due to lack of safety data and potential risks in this population. 1
Evidence on ARNI Use in Advanced CKD
- Current guidelines do not support the use of ARNI in patients with very low eGFR (<10), as most clinical trials excluded patients with severe renal impairment 1
- The STRONG-HF study, which investigated guideline-directed medical therapy (GDMT) implementation in heart failure with reduced ejection fraction (HFrEF), excluded patients with eGFR <30 mL/min/1.73m², indicating a lack of safety data for ARNI in severe renal dysfunction 1
- Evidence for cardiac medications, including ARNI, is limited in advanced CKD stages, particularly for eGFR <15 mL/min/1.73m² 1
Considerations for Patients on Dialysis
- Recent meta-analysis data from 2025 suggests potential benefits of ARNI in heart failure patients with end-stage kidney disease (ESKD) on maintenance dialysis, showing improvements in left ventricular ejection fraction and reduced all-cause mortality without significantly increasing risks of severe hyperkalemia or symptomatic hypotension 2
- However, this evidence is from observational studies and smaller trials, not large randomized controlled trials specifically designed to assess safety in patients with eGFR <10 2
Renal Effects of ARNI vs. Traditional RAS Inhibitors
- A 2025 systematic review and meta-analysis comparing ARNI with traditional renin-angiotensin system inhibitors (RASI) showed a 31% reduction in renal impairment with ARNI treatment and a 37% reduction in the odds of ≥50% decline in eGFR or progression to end-stage renal disease 3
- The UK HARP-III trial found that sacubitril/valsartan had similar effects on kidney function compared to irbesartan in patients with CKD, but this study included patients with eGFR 20-60 mL/min/1.73m², not those with eGFR <10 4
Hyperkalemia Risk and Monitoring
- ACE inhibitors, ARBs, and neprilysin inhibitors require careful monitoring for increased serum creatinine and hyperkalemia, particularly in patients with severely reduced kidney function 1
- The risk of hyperkalemia increases significantly as eGFR decreases below 30 mL/min/1.73m², making ARNI use potentially hazardous in patients with eGFR <10 1
Alternative Approaches for Heart Failure Management in Severe CKD
- For patients with heart failure and very low eGFR (<10), treatment should focus on other medications with better safety profiles in severe renal impairment 1
- SGLT2 inhibitors have demonstrated cardiovascular benefits in heart failure but are also not recommended for glucose lowering in patients with eGFR <30 mL/min/1.73m² 1
- In patients with severely reduced kidney function, careful consideration of the risk-benefit ratio for each medication is essential, with close monitoring if RAS inhibitors are deemed necessary 1
Practical Recommendations
- For patients with heart failure and eGFR <10 mL/min/1.73m², avoid initiating ARNI therapy due to insufficient safety data and increased risk of adverse effects 1
- If a patient is already on ARNI and experiences a decline in eGFR to <10 mL/min/1.73m², consider transitioning to alternative heart failure therapies with better established safety profiles in severe renal impairment 1
- For patients on dialysis with heart failure, consult with both nephrology and cardiology specialists before considering ARNI, as emerging data suggests potential benefits in this specific population that must be weighed against risks 2
ARNI therapy represents an important advancement in heart failure management, but its use in patients with eGFR <10 mL/min/1.73m² remains unsupported by current evidence and guidelines due to safety concerns and lack of data in this specific population.