What are the recommended antihypertensive medications and their maximum doses for patients with Chronic Kidney Disease (CKD)?

Antihypertensive Medications and Maximum Doses in CKD Patients

For patients with CKD and hypertension, ACE inhibitors or ARBs should be titrated to their maximum approved doses (e.g., lisinopril 40 mg daily, losartan 100 mg daily) to achieve optimal renoprotection, with blood pressure targets of <130/80 mmHg. 1, 2

Blood Pressure Targets

• Target BP should be <130/80 mmHg for all adults with CKD and hypertension 3, 1
• For patients with moderate-to-severe CKD (eGFR >30 mL/min/1.73 m²), aim for systolic BP of 120-129 mmHg if tolerated, as this provides additional cardiovascular and renal protection 1
• These targets are more aggressive than older guidelines and reflect newer evidence showing benefit from tighter control 1

First-Line Therapy: ACE Inhibitors or ARBs

Drug Selection and Dosing

ACE inhibitors are the preferred first-line agent for all CKD patients with hypertension 3, 1

• ACE inhibitors (or ARBs if not tolerated) are strongly recommended for CKD stage 3 or higher regardless of albuminuria 3, 1
• ACE inhibitors (or ARBs if not tolerated) are strongly recommended for CKD stage 1-2 with albuminuria ≥300 mg/d or ≥300 mg/g albumin-to-creatinine ratio 3, 1
• Administer ACE inhibitors or ARBs at the highest approved dose that is tolerated to achieve maximum renoprotective benefits 3, 1, 2

Maximum Doses by Renal Function

Lisinopril dosing in CKD: 4

• CrCl >30 mL/min: No dose adjustment needed; maximum dose 40 mg daily
• CrCl 10-30 mL/min: Start at 5 mg daily (half the usual dose); titrate to maximum 40 mg daily as tolerated
• CrCl <10 mL/min or hemodialysis: Start at 2.5 mg daily; titrate to maximum 40 mg daily as tolerated

Losartan dosing in CKD: 2

• Start at 50 mg once daily and titrate to 100 mg once daily for maximum renoprotective benefits
• For patients with moderately to severely increased albuminuria (A2-A3) with diabetes, start at 50 mg and increase to 100 mg once daily 2
• Continue losartan even when eGFR falls below 30 mL/min/1.73 m², unless symptomatic hypotension or uncontrolled hyperkalemia develops 2

Monitoring After Initiation

• Check blood pressure, serum creatinine, and serum potassium within 2-4 weeks of starting or increasing the dose of an ACE inhibitor or ARB 3, 1, 2
• Continue the ACE inhibitor or ARB unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase 1, 2
• Accept up to 30% increase in serum creatinine as this is expected and does not indicate harm 2

Second-Line and Third-Line Therapy

Add-On Therapy When BP Goal Not Achieved

Second-line: Add either a long-acting dihydropyridine calcium channel blocker OR a thiazide-type diuretic 1

Third-line: Add the other class not yet used (CCB or diuretic) 1

Diuretic Selection by CKD Stage

Loop diuretics (bumetanide, furosemide, torsemide) are preferred over thiazides in patients with moderate-to-severe CKD (GFR <30 mL/min) 3

• Bumetanide: 0.5-2 mg twice daily 3
• Furosemide: 20-80 mg twice daily 3
• Torsemide: 5-10 mg once daily 3

Thiazide-type diuretics can be used in earlier CKD stages 3, 5

• Chlorthalidone is preferred based on prolonged half-life and proven CVD reduction 3
• Monitor for hyponatremia, hypokalemia, uric acid, and calcium levels 3

Aldosterone Antagonists in Resistant Hypertension

For treatment-resistant hypertension, add spironolactone or eplerenone to the baseline regimen 3, 5

• Spironolactone: 25-100 mg once daily 3
• Eplerenone: 50-100 mg once or twice daily 3
• Avoid use with K+ supplements, other K-sparing diuretics, or significant renal dysfunction (GFR <45 mL/min for potassium-sparing diuretics) 3
• The risk of hyperkalemia restricts broad utilization in moderate-to-advanced CKD 5

Calcium Channel Blockers

Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker 6

• Avoid use of non-dihydropyridine CCBs (diltiazem, verapamil) in patients with HFrEF 3
• Amlodipine or felodipine may be used if required in HFrEF 3
• Associated with dose-related pedal edema, more common in women than men 3

Special Population Considerations

Black Patients with CKD

Initial therapy should include a thiazide-type diuretic or calcium channel blocker, either alone or in combination with an ACE inhibitor/ARB 1

Kidney Transplant Recipients

Use a dihydropyridine calcium channel blocker as first-line therapy, as this improves GFR and kidney survival in transplant patients 3, 1

• After kidney transplantation, treat to a BP goal of <130/80 mmHg 3

Elderly Patients (>80 years)

Apply the same BP targets and medication choices as younger patients, provided treatment is well tolerated 1

Critical Contraindications and Precautions

Absolute Contraindications

• Never combine an ACE inhibitor, ARB, and direct renin inhibitor together in CKD patients—this increases adverse events without additional benefit 3, 1
• ACE inhibitors and ARBs are absolutely contraindicated during pregnancy 3, 1
• Do not use ACE inhibitors if patient has history of angioedema with ACE inhibitors 3
• Do not use ARBs if patient has history of angioedema with ARBs 3

Use with Caution

• Increased risk of hyperkalemia with ACE inhibitors/ARBs, especially in patients with CKD or those on K+ supplements or K+-sparing drugs 3
• Risk of acute renal failure in patients with severe bilateral renal artery stenosis 3
• Use caution with ACE inhibitors/ARBs in patients with peripheral vascular disease due to association with renovascular disease 1

Managing Hyperkalemia

Hyperkalemia associated with ACE inhibitor/ARB use can often be managed with measures to reduce serum potassium rather than stopping the renin-angiotensin system blocker 1, 2

• Don't stop losartan or other ACE inhibitors/ARBs for mild creatinine increases (<30%): this is expected and does not indicate harm 2
• Manage potassium medically before reducing or stopping the medication 2

Common Pitfalls to Avoid

• Inadequate diuretic dosing leads to fluid retention and poor BP control, while excessive dosing causes volume contraction, hypotension, and worsening renal function 3, 1
• Don't underdose ACE inhibitors/ARBs: the proven renoprotective benefits in trials were achieved with maximum doses (e.g., losartan 100 mg daily), not lower doses 2
• Do not discontinue antihypertensive medications simply because BP falls below target if the patient tolerates the regimen without adverse effects—continue the effective therapy 1
• Avoid routine use of non-dihydropyridine CCBs with beta blockers because of increased risk of bradycardia and heart block 3
• Avoid potassium-sparing diuretics (amiloride, triamterene) in patients with significant CKD (GFR <45 mL/min) 3