From the Guidelines
I would consider decreasing or holding an ACE inhibitor when a patient's GFR drops by more than 30% from baseline or falls below 30 ml/min/1.73m², as recommended by the highest quality study available 1. This decision should be made after evaluating the patient's overall clinical status, including blood pressure control and the presence of proteinuria.
- Common ACE inhibitors include lisinopril, enalapril, ramipril, and benazepril.
- When a significant GFR decline occurs, I would first rule out other causes such as volume depletion, NSAID use, or urinary obstruction.
- If the GFR decline is attributed to the ACE inhibitor, I would either reduce the dose by 50% or temporarily discontinue it, then reassess kidney function within 1-2 weeks. The reason for this caution is that ACE inhibitors can reduce intraglomerular pressure by dilating the efferent arteriole, which normally helps protect the kidney long-term but can cause an acute drop in filtration pressure, as noted in 1 and 1. This effect is particularly pronounced in patients with bilateral renal artery stenosis, severe heart failure, or volume depletion. If the patient has significant proteinuria or heart failure, maintaining a reduced dose may be preferable to complete discontinuation due to the proven benefits in these conditions, as discussed in 1.
From the FDA Drug Label
Impaired renal function decreases elimination of lisinopril, which is excreted principally through the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30 mL/min. The disposition of enalapril and enalaprilat in patients with renal insufficiency is similar to that in patients with normal renal function until the glomerular filtration rate is 30 mL/min or less
Consideration for decreasing or holding an ACE inhibitor for GFR:
- A decrease in GFR to below 30 mL/min may require consideration of decreasing or holding the ACE inhibitor due to decreased elimination of the drug.
- It is essential to monitor renal function and adjust the dosage accordingly to avoid potential adverse effects.
- The decision to decrease or hold the ACE inhibitor should be made on a case-by-case basis, taking into account the individual patient's condition and response to treatment 2, 3.
From the Research
Decreasing or Holding ACE Inhibitor for GFR
- The decision to decrease or hold an ACE inhibitor for GFR depends on various factors, including the patient's CKD stage, serum potassium levels, and blood pressure 4.
- A study found that patients with CKD stage G4 (eGFR: 15-29 mL/min/1.73 m2) were 2.09-fold more likely to discontinue ACE-I/ARB therapy than those with eGFR ≥ 90 mL/min/1.73 m2 4.
- Hyperkalemia, hypotension, low bicarbonate level, and hospitalization (AKI-related, in particular) were associated with a higher risk of ACE-I/ARB discontinuation 4.
- Another study suggested that ACEI in combination with ARB is superior in reducing urine albumin excretion and urine protein excretion, but may be associated with decreased GFR and increased rates of hyperkalemia and hypotension 5.
- The use of ACEi/ARB in advanced CKD (eGFR ≤30 ml/min/1.73 m2) is still debated, and there is no clear evidence on the benefits and harms of continuing or discontinuing these medications in this population 6.
Factors to Consider
- CKD stage: Patients with more advanced CKD stages may be at higher risk of ACE-I/ARB discontinuation 4.
- Serum potassium levels: Hyperkalemia is a risk factor for ACE-I/ARB discontinuation 4.
- Blood pressure: Hypotension is a risk factor for ACE-I/ARB discontinuation 4.
- Hospitalization: AKI-related hospitalization is a risk factor for ACE-I/ARB discontinuation 4.