How are Angiotensin-Converting Enzyme (ACE) inhibitors managed in Chronic Kidney Disease (CKD)?

From the Guidelines

ACE inhibitors are a preferred treatment for hypertension in patients with chronic kidney disease (CKD), particularly those with albuminuria, and should be initiated at low doses and titrated gradually while closely monitoring kidney function and potassium levels. The use of ACE inhibitors in CKD is supported by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. This guideline recommends an ACE inhibitor (or an ARB, in case of ACE inhibitor intolerance) as a preferred drug for treatment of hypertension if albuminuria is present.

When using ACE inhibitors in CKD, it is essential to monitor serum creatinine and potassium levels, as these medications can cause a rise in creatinine and hyperkalemia. A rise in creatinine up to 30% from baseline is acceptable, but larger increases may require dose reduction or discontinuation 1. Potassium levels should be maintained below 5.5 mEq/L, with dietary counseling and possibly potassium binders if hyperkalemia develops.

Some key points to consider when using ACE inhibitors in CKD include:

• Initiating at low doses and titrating gradually
• Monitoring kidney function and potassium levels closely
• Avoiding the combination of ACE inhibitors and ARBs due to increased risk of hyperkalemia and AKI 1
• Being cautious in advanced CKD (eGFR <30 ml/min/1.73m²) and considering more frequent monitoring and potential discontinuation if kidney function deteriorates significantly or hyperkalemia becomes unmanageable

Overall, ACE inhibitors are a valuable treatment option for patients with CKD, but require careful management and monitoring to minimize potential risks and maximize benefits.

From the FDA Drug Label

1. 3 Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including lisinopril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving lisinopril and NSAID therapy.
2. 4 Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. In most patients no benefit has been associated with using two RAS inhibitors concomitantly In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on lisinopril and other agents that affect the RAS. Do not co-administer aliskiren with lisinopril in patients with diabetes. Avoid use of aliskiren with lisinopril in patients with renal impairment (GFR <60 ml/min).

Handling of ACE inhibitors in CKD:

• Monitor renal function periodically in patients with compromised renal function receiving ACE inhibitors, such as lisinopril, and NSAID therapy.
• Avoid combined use of RAS inhibitors, including ACE inhibitors and aliskiren, in patients with renal impairment (GFR <60 ml/min).
• Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and other agents that affect the RAS. 2

From the Research

Handling of ACE Inhibitors in CKD

• ACE inhibitors are commonly used in patients with chronic kidney disease (CKD) to slow the progression of renal damage 3, 4.
• The use of ACE inhibitors in CKD patients is associated with a reduced risk of dialysis and mortality 4, 5.
• However, ACE inhibitors can also increase the risk of hyperkalemia, cough, and hypotension in CKD patients 6, 5.

Monitoring of Serum Creatinine and Potassium

• Regular monitoring of serum creatinine and potassium is essential in CKD patients taking ACE inhibitors to minimize the risk of adverse effects 3, 6.
• A study found that serum creatinine was monitored in 91.6% of ACE inhibitor-treated patients, while potassium was monitored in only 38.1% 3.

Benefits and Risks of ACE Inhibitors in CKD

• ACE inhibitors have been shown to reduce the risk of kidney events, cardiovascular events, cardiovascular death, and all-cause death in non-dialysis CKD patients 5.
• However, the use of ACE inhibitors in CKD patients requires careful consideration of the potential benefits and risks, including the risk of hyperkalemia and other adverse effects 6, 5.

Comparison with Other Antihypertensive Drugs

• ACE inhibitors have been compared to other antihypertensive drugs, including calcium channel blockers, beta-blockers, and diuretics, in terms of their effectiveness in reducing kidney and cardiovascular outcomes in CKD patients 5.
• The results of these comparisons suggest that ACE inhibitors may have a higher benefit-to-risk ratio than other antihypertensive drugs in non-dialysis CKD patients 5.