What are alternative treatments to amlodipine (Calcium Channel Blocker)/benazepril (Angiotensin-Converting Enzyme Inhibitor) for Hypertension (HTN) management in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

For patients with Chronic Kidney Disease (CKD), alternatives to amlodipine/benazepril for hypertension management include Renin-Angiotensin System Inhibitors (RASI) such as Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin II Receptor Blockers (ARBs), which have been shown to reduce cardiovascular event rates and kidney end points 1.

Key Considerations

• The choice of initial therapy should be based on the presence or absence of diabetes and proteinuria, with RASI therapy recommended for patients with high blood pressure, CKD, and severely increased albuminuria without diabetes 1.
• For patients with CKD and moderately increased albuminuria without diabetes, RASI therapy is suggested, although the evidence is weaker 1.
• Combining an ARB with an ACE inhibitor may be beneficial for patients with significant proteinuria, but requires careful monitoring of potassium and renal function.

Treatment Options

• ARBs like losartan (50-100 mg daily) or valsartan (80-320 mg daily) are good options for CKD patients, providing renoprotective effects similar to ACE inhibitors but with fewer side effects like cough.
• Non-dihydropyridine calcium channel blockers such as diltiazem or verapamil can also be considered.
• Diuretics like chlorthalidone (12.5-25 mg daily) or a mineralocorticoid receptor antagonist like spironolactone (25-50 mg daily) can be added for resistant hypertension.

Monitoring and Adjustments

• Regular monitoring of blood pressure, renal function, and electrolytes is essential, especially when initiating or adjusting these medications.
• Dose adjustments may be necessary based on the patient's estimated glomerular filtration rate (eGFR).

Evidence-Based Recommendations

• The 2021 KDIGO clinical practice guideline recommends starting RASI therapy for people with high blood pressure, CKD, and severely increased albuminuria without diabetes 1.
• The guideline suggests starting RASI therapy for people with high blood pressure, CKD, and moderately increased albuminuria without diabetes, although the evidence is weaker 1.

From the Research

Alternative Treatments for Hypertension in CKD Patients

• Angiotensin II receptor antagonists, such as losartan, have been shown to have renoprotective effects in patients with CKD and hypertension, reducing proteinuria and slowing the progression of renal disease 2, 3.
• Angiotensin-converting enzyme (ACE) inhibitors are recommended as a first-line antihypertensive approach in patients with CKD, as they have beneficial effects on proteinuria and declining renal function 4, 5.
• Non-dihydropyridine calcium channel blockers (CCBs) consistently reduce albuminuria and slow the decline in kidney function, while dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker 5.
• Benidipine, an L- and T-type calcium channel blocker, has been shown to have antiproteinuric effects when administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3-5 CKD 6.
• Diuretics are commonly used and represent the cornerstone in the management of CKD patients, and can be used in combination with other antihypertensive medications to achieve blood pressure goals 5.

Comparison of Alternative Treatments

• Losartan has been compared to amlodipine in patients with CKD and hypertension, and has been shown to have a greater reduction in proteinuria and a more pronounced renoprotective effect 2, 3.
• Benidipine has been compared to amlodipine in hypertensive patients with stage 3-5 CKD, and has been shown to have a greater antiproteinuric effect when administered in combination with angiotensin receptor blockers 6.

Treatment Considerations

• The choice of antihypertensive medication in CKD patients should be based on the individual patient's characteristics, including the level of proteinuria, blood pressure, and presence of other comorbidities 4, 5.
• A combination of antihypertensive medications, including ACE inhibitors, ARBs, CCBs, and diuretics, may be necessary to achieve blood pressure goals and provide optimal renoprotection in CKD patients 5.