From the Guidelines
Enalapril should not be discontinued until the glomerular filtration rate (GFR) falls below 30 mL/min/1.73m², as continuation of the medication may provide cardiovascular benefit without significantly increasing the risk of end-stage kidney disease, as suggested by the most recent guidelines 1. When considering the management of Enalapril in patients with declining kidney function, it's crucial to weigh the benefits of continued therapy against the potential risks. The primary concern with ACE inhibitors like Enalapril in patients with reduced kidney function is the potential for worsening renal function, hyperkalemia, and acute kidney injury. However, recent guidelines suggest that the benefits of ACE inhibitors can extend to patients with lower levels of kidney function than previously thought, particularly in those with albuminuria or at high risk of cardiovascular events.
Key considerations for managing Enalapril in patients with kidney impairment include:
- Monitoring kidney function and potassium levels closely, especially when the GFR is below 60 mL/min/1.73m².
- Being aware that the risk of adverse effects increases as kidney function declines, but the medication can still offer protection against progressive kidney disease and cardiovascular events until the GFR falls below 30 mL/min/1.73m², as indicated by recent standards of care 1.
- Understanding that dose adjustment may be necessary as kidney function changes, but complete discontinuation is not recommended solely based on a GFR above 30 mL/min/1.73m².
The rationale behind continuing Enalapril in patients with a GFR below 30 mL/min/1.73m², if tolerated, is based on its nephroprotective effects and the potential to reduce the risk of cardiovascular events, as outlined in recent clinical practice guidelines 1. However, the decision to continue or discontinue Enalapril should be individualized, taking into account the patient's overall clinical condition, the presence of albuminuria, and their risk profile for cardiovascular disease. Regular monitoring and adjustment of therapy as needed are critical to balancing the benefits and risks of Enalapril in patients with impaired kidney function.
From the Research
Discontinuation of Enalapril based on GFR
- The decision to discontinue Enalapril due to a specific glomerular filtration rate (GFR) is complex and depends on various factors, including the presence of hyperkalemia, hypotension, or rapid worsening of eGFR 2.
- According to a study published in 2019, Enalapril can be continued in patients with advanced chronic kidney disease (eGFR less than 15 ml/min/1.73 m) unless hyperkalemia ensues unresponsive to therapy, hypotension develops, or there is an unusually rapid worsening of eGFR 2.
- Another study from 1990 found that Enalapril caused a fall in GFR, which was clinically acceptable in most patients, with a median change in GFR of -14% (range -44% to +10%) 3.
- A 2005 study suggested that a low concentration of Enalaprilat afforded the same degree of renoprotection, blood pressure control, and minimization of proteinuria as a high concentration, during 12 months of follow-up, in patients with moderate to severe renal insufficiency 4.
- A 2019 study found that in patients with heart failure with reduced ejection fraction, Enalapril was associated with decreased risk of mortality and heart failure hospitalizations, even with up to a 10% decline in eGFR 5.
- The risk of hyperkalemia in nondiabetic patients with chronic kidney disease receiving Enalapril is small, particularly if baseline and follow-up GFR is higher than 40 mL/min/1.73 m 6.
Factors Influencing Discontinuation
- Hyperkalemia: Enalapril should be discontinued if hyperkalemia ensues unresponsive to therapy 2.
- Hypotension: Enalapril should be discontinued if hypotension develops 2.
- Rapid worsening of eGFR: Enalapril should be discontinued if there is an unusually rapid worsening of eGFR 2.
- GFR less than 15 ml/min/1.73 m: Enalapril can be continued in patients with advanced chronic kidney disease unless hyperkalemia, hypotension, or rapid worsening of eGFR occurs 2.