What are the considerations for reducing the dose of lisinopril (Angiotensin-Converting Enzyme Inhibitor) in a patient with Chronic Kidney Disease (CKD) and hypertension?

From the Guidelines

Lisinopril dose should not be lowered in CKD patients with hypertension, but rather titrated to the maximal tolerated dose, with close monitoring of serum potassium and serum creatinine levels within 2 to 4 weeks of initiation of or change in dose. This approach is supported by the 2020 KDIGO clinical practice guideline, as reported in the Annals of Internal Medicine in 2021 1. The guideline emphasizes the importance of using RAS inhibitors, such as lisinopril, in patients with diabetes, hypertension, and albuminuria, and titrating them to the maximal tolerated dose.

Key considerations when adjusting lisinopril in CKD patients include:

• Monitoring serum creatinine and potassium levels within 2 to 4 weeks after initiation or dose changes, as ACE inhibitors can cause acute kidney injury or hyperkalemia in these patients 1
• Aiming for blood pressure targets of <130/80 mmHg in most CKD patients with hypertension
• Being aware that combination therapy with ACEis and ARBs is harmful and should be avoided in patients with diabetes and CKD 1
• Considering alternative antihypertensive agents, such as mineralocorticoid receptor antagonists, for patients with resistant hypertension 1

It is also important to note that although serum creatinine level may increase during drug initiation or dose titration, RAS inhibitors may be continued unless the creatinine level increases by more than 30% 1. The dose should be reduced or withdrawn in those who develop significant hyperkalemia or experience a >30% increase in serum creatinine after starting or increasing lisinopril.

From the FDA Drug Label

1. 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.

The recommended approach for lowering the lisinopril dose in a CKD patient with hypertension is to reduce the dose if the patient's creatinine clearance is between 10 mL/min and 30 mL/min. The dose should be reduced to half of the usual recommended dose, which is 5 mg for hypertension. The dose can then be up-titrated as tolerated to a maximum of 40 mg daily 2.

• Key considerations:
  • Creatinine clearance: The dose adjustment is based on the patient's creatinine clearance.
  • Initial dose reduction: The initial dose should be reduced to half of the usual recommended dose.
  • Up-titration: The dose can be up-titrated as tolerated to a maximum of 40 mg daily.

From the Research

Lowering Lisinopril Dose in CKD Patient with Hypertension

• The decision to lower the lisinopril dose in a CKD patient with hypertension should be based on individual patient characteristics and blood pressure goals 3, 4.
• According to recent guidelines, the recommended blood pressure goal for CKD patients is <130/80 mmHg 4, 5.
• Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is often used as a first-line treatment for hypertension in CKD patients 4, 5.
• The dose of lisinopril should be adjusted based on the patient's blood pressure response and kidney function 5, 6.
• Close monitoring of blood pressure and kidney function is essential when adjusting the dose of lisinopril in CKD patients 5, 6.
• Combination therapy with other antihypertensive agents, such as diuretics or calcium channel blockers, may be necessary to achieve blood pressure goals in CKD patients 4, 6.

Considerations for Dose Adjustment

• The presence of proteinuria or albuminuria may require a more aggressive approach to blood pressure control, including the use of ACE inhibitors or angiotensin II receptor blockers (ARBs) 4, 5.
• Patients with CKD and hypertension may require more frequent monitoring of blood pressure and kidney function to adjust the dose of lisinopril and other antihypertensive agents 5, 6.
• The use of novel therapies, such as non-steroidal mineralocorticoid receptor antagonists or dual endothelin receptor antagonists, may offer alternative treatment options for CKD patients with hypertension 6.