What is the safety of Lisinopril (Angiotensin-Converting Enzyme Inhibitor) in patients with Chronic Kidney Disease (CKD) Stage 5, also known as End-Stage Renal Disease (ESRD)?

From the Guidelines

Lisinopril is generally not recommended for patients with CKD Stage 5 (eGFR <15 ml/min/1.73m²) due to significant safety concerns, as stated in the 2020 KDIGO clinical practice guideline 1. In advanced kidney disease, ACE inhibitors like lisinopril can worsen kidney function, cause dangerous hyperkalemia, and contribute to metabolic acidosis. If blood pressure control is necessary in CKD Stage 5, alternative antihypertensive medications such as calcium channel blockers (amlodipine 5-10mg daily) or beta-blockers (metoprolol 25-100mg twice daily) are typically safer options. For patients already on lisinopril who progress to Stage 5 CKD, the medication should be discontinued or significantly reduced with close monitoring of potassium levels, kidney function, and blood pressure. The physiological reason for this caution is that ACE inhibitors dilate the efferent arteriole in the glomerulus, which reduces glomerular filtration pressure - a mechanism that becomes problematic when kidney function is already severely compromised. Some key points to consider when managing patients with CKD Stage 5 include:

• Monitoring serum creatinine and potassium levels during RAS inhibitor treatment or dose escalation, as recommended in the 2020 KDIGO clinical practice guideline 1.
• Avoiding combination therapy with ACEis and ARBs, as it is harmful and should be avoided in patients with diabetes and CKD 1.
• Considering alternative antihypertensive medications, such as calcium channel blockers or beta-blockers, for blood pressure control in CKD Stage 5.
• Being aware of the potential risks and benefits of using RAS inhibitors in patients with CKD Stage 5, and carefully weighing these factors in individual patient management decisions 1. In dialysis patients, some nephrologists may occasionally use low-dose lisinopril (2.5-5mg) for specific indications, but this requires extremely careful monitoring and should only be done under specialist supervision. It is also important to note that the use of RAS inhibitors, including lisinopril, should be individualized and based on a thorough assessment of the patient's clinical condition, including their kidney function, blood pressure, and other comorbidities 1. Overall, the safety of lisinopril in patients with CKD Stage 5 is a complex issue that requires careful consideration of the potential benefits and risks, as well as close monitoring and individualized management.

From the FDA Drug Label

5.3 Impaired Renal Function Monitor renal function periodically in patients treated with lisinopril. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on lisinopril. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on lisinopril [see Adverse Reactions (6. 1), Drug Interactions (7.4)].

The safety of Lisinopril in patients with Chronic Kidney Disease (CKD) Stage 5, also known as End-Stage Renal Disease (ESRD), requires careful consideration due to the potential risk of acute renal failure.

• Monitoring of renal function is necessary in these patients.
• Dose adjustment of lisinopril is required in patients undergoing hemodialysis or whose creatinine clearance is ≤ 30 mL/min 2.
• Patients with CKD may be at particular risk of developing acute renal failure on lisinopril. It is recommended to withhold or discontinue therapy in patients who develop a clinically significant decrease in renal function on lisinopril.

From the Research

Safety of Lisinopril in Patients with CKD Stage 5

• The safety of Lisinopril in patients with Chronic Kidney Disease (CKD) Stage 5, also known as End-Stage Renal Disease (ESRD), has been evaluated in several studies 3, 4, 5, 6.
• A study published in 2010 found that the risk of hyperkalemia (elevated serum potassium level) increased gradually with declining eGFR, but there was no apparent threshold for contraindicating ACE-inhibitors like Lisinopril 3.
• Another study published in 1994 found that adjusting the dose of Lisinopril according to the individual creatinine clearance prevented significant accumulation of the drug in patients with advanced renal failure 4.
• A study published in 1987 found that Lisinopril accumulated in patients with severe renal failure, and recommended adjusting the dose or dosing frequency to avoid excessive administration 5.
• Another study published in 1987 found that Lisinopril was effective in reducing blood pressure in patients with impaired renal function, but noted a tendency towards drug accumulation in patients with severe renal impairment 6.
• However, it's worth noting that the most recent study provided 7 does not directly address the safety of Lisinopril in patients with CKD Stage 5, but rather evaluates the effectiveness and safety of Sacubitril/Valsartan in patients with CKD.

Key Findings

• Lisinopril can accumulate in patients with severe renal failure, and dose adjustment is recommended to avoid excessive administration 4, 5, 6.
• The risk of hyperkalemia increases with declining eGFR, but there is no apparent threshold for contraindicating ACE-inhibitors like Lisinopril 3.
• Lisinopril is effective in reducing blood pressure in patients with impaired renal function, but requires careful dose adjustment to avoid accumulation 5, 6.