At what glomerular filtration rate (GFR) should Lisinopril (Angiotensin-Converting Enzyme Inhibitor) be stopped or adjusted in patients with chronic kidney disease (CKD)?

From the Guidelines

Lisinopril should be continued in patients with chronic kidney disease (CKD) even when the estimated glomerular filtration rate (eGFR) falls below 30 ml/min per 1.73 m², but consideration for dose reduction or discontinuation should be given when eGFR is less than 15 ml/min per 1.73 m², or in the presence of symptomatic hypotension, uncontrolled hyperkalemia, or to reduce uremic symptoms while treating kidney failure 1. When managing patients with CKD on lisinopril, it is crucial to monitor changes in blood pressure, serum creatinine, and serum potassium within 2–4 weeks of initiation or increase in the dose of a RASi (Renin-Angiotensin System inhibitor), depending on the current GFR and serum potassium 1. Key considerations for adjusting or stopping lisinopril in CKD patients include:

• Monitoring for hyperkalemia, which can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping RASi 1.
• Avoiding discontinuation of ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose 1.
• Being cautious of the potential for lisinopril to cause further decline in GFR, acute kidney injury, particularly in patients with bilateral renal artery stenosis or volume depletion, but also recognizing its cardioprotective and antiproteinuric benefits in advanced CKD 1. Given the most recent and highest quality evidence from the kdigo 2024 clinical practice guideline for the evaluation and management of chronic kidney disease 1, the approach to lisinopril use in CKD emphasizes the importance of individualized risk-benefit assessment, particularly in patients with severe CKD, to maximize the benefits of RASi therapy while minimizing its risks.

From the FDA Drug Label

Doses above 0.61 mg per kg (or in excess of 40 mg) have not been studied in pediatric patients [see Clinical Pharmacology (12. 3)]. Lisinopril tablets are not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m2 [see Use in Specific Populations (8.4)and Clinical Studies (14.1)]. 2. 4 Dose in Patients with Renal Impairment No dose adjustment of lisinopril tablets is required in patients with creatinine clearance > 30 mL/min. In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of lisinopril tablets to half of the usual recommended dose i.e., hypertension, 5 mg; systolic heart failure, 2.5 mg and acute MI, 2. 5 mg. Up titrate as tolerated to a maximum of 40 mg daily. For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily [see Use in Specific Populations (8.7)and Clinical Pharmacology (12.3)].

Lisinopril should be stopped or adjusted in patients with chronic kidney disease (CKD) when the glomerular filtration rate (GFR) is less than 30 mL/min/1.73m2 or when the creatinine clearance is less than 10 mL/min.

• For patients with a GFR between 10 mL/min and 30 mL/min, the initial dose of lisinopril should be reduced to half of the usual recommended dose.
• For patients on hemodialysis or with a creatinine clearance less than 10 mL/min, the recommended initial dose is 2.5 mg once daily 2.

From the Research

Stopping Lisinopril in Chronic Kidney Disease

The decision to stop Lisinopril in patients with chronic kidney disease (CKD) depends on various factors, including the patient's glomerular filtration rate (GFR) and overall health condition.

• GFR Considerations: Studies have shown that Lisinopril can be effective in patients with impaired renal function, with a GFR of 60 ml/minute or less 3, 4. However, the dose may need to be adjusted based on the pretreatment GFR, and a decrease in dosage should be considered with prolonged treatment 5.
• Dose Adjustment: In patients with severe renal failure, adjustment of the dose or the dosing frequency to the degree of renal failure is recommended to avoid administration of doses in excess of those required to achieve adequate inhibition of converting enzyme 6.
• Monitoring Kidney Function: Regular monitoring of kidney function, including GFR, is essential in patients with CKD taking Lisinopril. If the GFR declines significantly, the dose of Lisinopril may need to be adjusted or the medication stopped altogether.
• Individualized Approach: The decision to stop Lisinopril in patients with CKD should be made on an individual basis, taking into account the patient's specific health condition, response to treatment, and potential risks and benefits of continuing or discontinuing the medication.

Key Findings

• Lisinopril can be effective in patients with impaired renal function, with a GFR of 60 ml/minute or less 3, 4.
• The dose of Lisinopril may need to be adjusted based on the pretreatment GFR, and a decrease in dosage should be considered with prolonged treatment 5.
• In patients with severe renal failure, adjustment of the dose or the dosing frequency to the degree of renal failure is recommended to avoid administration of doses in excess of those required to achieve adequate inhibition of converting enzyme 6.
• Regular monitoring of kidney function, including GFR, is essential in patients with CKD taking Lisinopril 7.