What is the role of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme inhibitors (ACE) in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

Angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) are the recommended first-line medications for chronic kidney disease (CKD) patients, especially those with proteinuria or diabetes, as they reduce both cardiovascular event rates and kidney end points, as supported by the 2021 KDIGO clinical practice guideline 1.

Key Considerations

• The strength of evidence for the benefit of RASI (ACEIs and ARBs) varies according to the presence or absence of diabetes and proteinuria, with strong evidence in CKD subpopulations with low eGFR and severely increased albuminuria 1.
• For patients with high blood pressure, CKD, and severely increased albuminuria (CKD G1 to G4; albuminuria category A3) without diabetes, starting RASI therapy (ACEI or ARB) is recommended (1B) 1.
• The choice of initial therapy is limited to RASI, with no randomized controlled trials (RCTs) comparing different combination therapies in CKD 1.

Medication Selection and Monitoring

• Common ARBs include losartan (25-100 mg daily), valsartan (80-320 mg daily), and irbesartan (150-300 mg daily), while common ACEIs include lisinopril (10-40 mg daily), enalapril (5-40 mg daily), and ramipril (2.5-20 mg daily) 2.
• When starting either medication, monitor blood pressure, serum potassium, and kidney function (creatinine) within 1-2 weeks of initiation, and watch for side effects including hyperkalemia, cough (more common with ACEIs), angioedema, and hypotension.

Special Considerations

• ARBs and ACEIs should not be used together due to increased adverse effects without additional benefits, as supported by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report 2.
• For patients with significant proteinuria who don't achieve adequate reduction on maximum doses, adding a sodium-glucose cotransporter-2 (SGLT2) inhibitor may provide additional kidney protection.

From the FDA Drug Label

7.4 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, syncope, 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.

Key Points:

• Dual blockade of the RAS with ARBs and ACE inhibitors is associated with increased risks of hypotension, hyperkalemia, and changes in renal function.
• In most patients, no benefit has been associated with using two RAS inhibitors concomitantly.
• Avoid combined use of RAS inhibitors, such as ARBs and ACE inhibitors, in patients with CKD.
• Closely monitor blood pressure, renal function, and electrolytes in patients on ARBs and ACE inhibitors. 3 4

From the Research

Use of ARBs and ACE Inhibitors in CKD Patients

• The use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients with chronic kidney disease (CKD) has been shown to slow the progression of renal disease 5.
• ACE inhibitors have been found to reduce the risk of worsening renal function by 55-75% in patients with CKD, with the greatest benefit seen in those with the most advanced renal insufficiency 5.
• ARBs have also been shown to be effective in reducing the progression of CKD, with a meta-analysis of 109 studies finding that ARBs may prevent kidney failure and reduce the risk of doubling of serum creatinine 6.

Safety Considerations

• The main adverse effects of ACE inhibitors and ARBs are hypotension, renal function impairment, and hyperkalemia 7.
• Patients with CKD who receive ACE inhibitors or ARBs are at increased risk of hyperkalemia, particularly if they have heart failure or are taking other medications that increase potassium levels 5.
• The use of ACE inhibitors or ARBs in patients with advanced CKD (GFR <30 mL/min) requires careful monitoring of renal function and electrolyte levels 8.

Clinical Recommendations

• ACE inhibitors or ARBs should be considered as first-line therapy in patients with CKD, particularly those with proteinuria or heart failure 5, 8.
• The decision to use ACE inhibitors or ARBs in patients with CKD should be based on individual patient characteristics, including the severity of renal insufficiency, presence of proteinuria, and other comorbidities 7, 9.
• Patients with CKD who are treated with ACE inhibitors or ARBs should be closely monitored for adverse effects, including changes in renal function, electrolyte levels, and blood pressure 5, 7.