ARNI Therapy Management Based on Serum Creatinine Levels
ARNI therapy should be held when serum creatinine increases by ≥30% from baseline within the first 2 months of therapy, and should be discontinued permanently if serum creatinine rises by ≥50% from baseline or reaches ≥4.0 mg/dL. 1, 2, 3
Monitoring Recommendations
When initiating or continuing ARNI therapy:
- Monitor serum creatinine before every dose initially, then regularly during treatment
- Establish baseline serum creatinine before starting therapy
- Expect potential increases in serum creatinine during the first 2-4 weeks of therapy
- Evaluate for alternative causes of acute kidney injury when creatinine rises
Specific Thresholds for ARNI Management
When to Hold ARNI Therapy
- Serum creatinine increase of ≥30% from baseline within first 2 months of therapy
- Signs of volume depletion or hypotension
- Concomitant use of nephrotoxic medications (NSAIDs, contrast media)
When to Discontinue ARNI Therapy
- Serum creatinine increase ≥50% from baseline
- Absolute serum creatinine ≥4.0 mg/dL
- Development of hyperkalemia (serum potassium ≥5.6 mmol/L)
- Need for renal replacement therapy
Expected Creatinine Changes with ARNI Therapy
It's important to understand that some increase in serum creatinine is expected and may actually correlate with long-term renoprotection:
- Patients with normal renal function: Expect ~10% increase in serum creatinine
- Patients with renal insufficiency: Expect up to 25% increase in serum creatinine
- Most increases occur within first 2 weeks (
15%) with more gradual increases (10%) in weeks 3-4 - Creatinine typically stabilizes after approximately 4 weeks of therapy 1, 3
Clinical Pearls and Pitfalls
- Do not discontinue ARNI for minor increases in serum creatinine (<30%) in the absence of volume depletion 4
- Small elevations in serum creatinine with RAS blockers must not be confused with acute kidney injury 4
- Patients with baseline renal insufficiency may show greater initial rises in creatinine but often derive the most benefit from ARNI therapy 2
- Consider temporarily holding ARNI during acute illness, dehydration, or when using contrast media
- Monitor potassium levels closely, especially in patients with eGFR <60 mL/min/1.73m² 4
Special Considerations
- Elderly patients may have lower GFR at relatively normal-appearing creatinine levels and require closer monitoring
- Concomitant diuretic use reduces risk of hyperkalemia but increases risk of prerenal azotemia
- Real-world data from Taiwan shows ARNI appears safe regarding renal function even in patients with higher baseline creatinine (mean 1.5 mg/dL) 5
- Recent evidence suggests continuation of ARNI therapy despite acute increases in creatinine may still provide long-term cardiovascular benefits 6
By following these guidelines for monitoring and managing serum creatinine levels during ARNI therapy, you can maximize the benefits while minimizing risks of adverse renal outcomes.