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 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.
• Many patients with CKD will require combination therapy to achieve the systolic blood pressure (SBP) target of less than 120 mm Hg, but evidence-based recommendations are limited to the choice of initial therapy 1.
• For people 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.

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) 1.
• When starting these medications, monitor blood pressure, serum potassium, and kidney function (creatinine) within 1-2 weeks of initiation, and be cautious in patients with bilateral renal artery stenosis, and avoid these medications during pregnancy.
• A rise in creatinine up to 30% is acceptable if it stabilizes, and these medications should be continued indefinitely as long as they're tolerated and beneficial, with dose adjustments based on blood pressure control and kidney function.

Additional Considerations

• While ARBs and ACEIs have similar efficacy, ARBs typically cause less cough as a side effect, and the combination of ACEIs and ARBs is not recommended due to the increased risk of hyperkalemia and acute kidney injury (AKI) 1.
• The American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) recommend an ACEI or ARB for treatment of hypertension among people with type 1 or type 2 diabetes who have hypertension and albumin-to-creatinine ratio (ACR) ≥30 mg/g 1.

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. 2 3

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 4.
• ACE inhibitors have been found to be effective in reducing the risk of kidney failure and cardiovascular events in patients with CKD stages 3-5 5.
• ARBs have also been shown to prevent kidney failure and the progression from microalbuminuria to macroalbuminuria in patients with diabetes and kidney disease 6.

Safety of ACE Inhibitors in CKD Patients

• The main adverse effects of ACE inhibitors are hypotension, renal function impairment, and hyperkalemia 7.
• The risk of hyperkalemia is higher in patients with CKD who receive ACE inhibitors, especially those with heart failure or diabetes 4.
• The use of ACE inhibitors in patients with CKD stage 5 has been found to slow the progression of renal damage, but the benefits and risks need to be carefully evaluated 8.

Comparison of ACE Inhibitors and ARBs

• ACE inhibitors have been found to be more effective than ARBs in reducing the risk of kidney events and cardiovascular outcomes in non-dialysis CKD patients 5.
• ARBs have been found to be effective in preventing kidney failure and the progression from microalbuminuria to macroalbuminuria in patients with diabetes and kidney disease 6.
• The combination of ACE inhibitors and ARBs has been found to increase the risk of hyperkalemia and hypotension, and its benefits and risks need to be carefully evaluated 5.

Clinical Implications

• ACE inhibitors and ARBs should be used with caution in patients with CKD, especially those with heart failure or diabetes, due to the risk of hyperkalemia and hypotension 4, 7.
• The use of ACE inhibitors and ARBs in patients with CKD should be individualized, taking into account the patient's underlying disease and comorbidities 8, 5.
• Further studies are needed to fully evaluate the benefits and risks of ACE inhibitors and ARBs in patients with CKD, especially in those with advanced disease 6, 5.