Is perindopril suitable for patients with impaired renal function?

From the Guidelines

Perindopril can be used in patients with impaired renal function, but dose adjustment is necessary based on creatinine clearance. For patients with mild impairment (creatinine clearance ≥30 mL/min), the maximum recommended dose is 4 mg daily. For those with moderate to severe impairment (creatinine clearance <30 mL/min), the dose should be reduced to 2 mg daily, which may be titrated up to 4 mg daily if needed and tolerated. Close monitoring of renal function, potassium levels, and blood pressure is essential during treatment, especially when initiating therapy or adjusting doses. Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, affects kidney hemodynamics by reducing efferent arteriolar resistance, which can temporarily decrease glomerular filtration rate, particularly in patients with renal artery stenosis, severe heart failure, or volume depletion. Patients with renal impairment are also at higher risk for hyperkalemia and further deterioration of renal function, so regular laboratory monitoring is crucial. Treatment should be initiated at a low dose with gradual titration while monitoring for adverse effects, as supported by the most recent study 1.

Some key points to consider when using perindopril in patients with impaired renal function include:

• The importance of regular monitoring of renal function, potassium levels, and blood pressure
• The need for dose adjustment based on creatinine clearance
• The potential for perindopril to affect kidney hemodynamics and increase the risk of hyperkalemia and further deterioration of renal function
• The benefits of using perindopril in patients with impaired renal function, including reducing the risk of cardiovascular events and slowing the progression of kidney disease, as shown in studies such as the ADVANCE trial 1.

It is also important to note that the use of perindopril in patients with impaired renal function should be individualized, taking into account the patient's specific clinical characteristics and medical history, as recommended in the 2025 standards of care in diabetes 1.

From the FDA Drug Label

The dosage may be titrated upward until blood pressure, when measured just before the next dose, is controlled or to a maximum of 16 mg per day. Kinetic data indicate that perindoprilat elimination is decreased in renally impaired patients, with a marked increase in accumulation when creatinine clearance drops below 30 mL/min. In such patients (creatinine clearance <30 mL/min), safety and efficacy of perindopril erbumine tablets have not been established For patients with lesser degrees of impairment (creatinine clearance above 30 mL/min), the initial dosage should be 2 mg/day and dosage should not exceed 8 mg/day due to limited clinical experience.

Perindopril is not suitable for patients with severe impaired renal function (creatinine clearance <30 mL/min), as safety and efficacy have not been established in this population 2. For patients with mild to moderate impaired renal function (creatinine clearance above 30 mL/min), the initial dosage should be 2 mg/day and should not exceed 8 mg/day.

From the Research

Perindopril and Impaired Renal Function

• Perindopril is an angiotensin converting enzyme inhibitor (ACEI) that has been studied in patients with impaired renal function 3, 4.
• In patients with chronic renal failure, perindopril was well tolerated and did not alter creatinine clearance 4.
• However, the pharmacokinetics of perindoprilat, the active metabolite of perindopril, were altered in patients with renal impairment, with a significant correlation between the renal clearance of perindoprilat and creatinine clearance 4.
• A study in hypertensive patients with stable chronic renal failure found that perindopril 2 or 4 mg once a day did not affect renal function, but the serum accumulation ratio of perindoprilat was higher in patients with severe renal failure 4.

Renal Protection with Perindopril

• Perindopril has been shown to have renoprotective effects in diabetic patients, particularly when used in combination with indapamide 5.
• The fixed-dose combination of perindopril and indapamide (Preterax) has been found to reduce urinary albumin excretion and prevent nephropathy in diabetic patients, independently of blood pressure control 5.
• The use of perindopril in patients with impaired renal function requires careful monitoring of renal function and adjustment of the dose as needed 3, 4.

Key Findings

• Perindopril is generally well tolerated in patients with impaired renal function, but requires careful monitoring of renal function and dose adjustment as needed 3, 4.
• The combination of perindopril and indapamide (Preterax) may be beneficial in reducing urinary albumin excretion and preventing nephropathy in diabetic patients 5.
• Further research is needed to fully understand the effects of perindopril on renal function in patients with impaired renal function 3, 4.