Antihypertensive Medications and Dosing in Chronic Kidney Disease
In CKD patients, start with an ACE inhibitor or ARB as first-line therapy when albuminuria ≥30 mg/24h is present, titrate to full dose before adding a dihydropyridine calcium channel blocker, then add a thiazide-like diuretic, with spironolactone reserved for resistant hypertension—all while targeting BP <130/80 mmHg in most patients with moderate-to-severe CKD. 1
Blood Pressure Targets Based on CKD Stage and Albuminuria
Non-Diabetic CKD Patients
For patients without significant albuminuria (<30 mg/24h):
- Target BP ≤140/90 mmHg 1
- This applies to CKD patients at lower risk of progression
For patients with moderate albuminuria (30-300 mg/24h):
- Target BP ≤130/80 mmHg 1
- Lower targets reduce proteinuria and slow progression
For patients with severe albuminuria (≥300 mg/24h):
- Target BP ≤130/80 mmHg 1
- This is a strong recommendation (1B evidence) given the high risk of progression
Diabetic CKD Patients
For diabetic patients without albuminuria (<30 mg/24h):
- Target BP <140/90 mmHg 1
For diabetic patients with any albuminuria (≥30 mg/24h):
- Target BP <130/80 mmHg 1
- The 2024 ESC guidelines recommend targeting systolic BP 120-129 mmHg in diabetic patients receiving BP-lowering drugs if tolerated 1
Updated 2024 Targets for Moderate-to-Severe CKD
The most recent 2024 ESC guidelines recommend:
- Target systolic BP 120-129 mmHg for patients with moderate-to-severe CKD and eGFR >30 mL/min/1.73 m², if tolerated 1
- This represents a more aggressive target than older KDIGO recommendations
- Individualized BP targets are recommended for those with eGFR <30 mL/min/1.73 m² or renal transplantation 1
Stepwise Pharmacological Approach
Step 1: ACE Inhibitor or ARB (First-Line)
For all CKD patients with albuminuria ≥30 mg/24h:
- Start with low-dose ACE inhibitor or ARB 1
- This is a strong recommendation (1B) for albuminuria ≥300 mg/24h 1
- For moderate albuminuria (30-300 mg/24h), this is suggested (2D evidence) 1
Common starting doses:
- Lisinopril 10 mg daily, titrate to 40 mg daily
- Enalapril 5 mg daily, titrate to 20 mg twice daily
- Losartan 50 mg daily, titrate to 100 mg daily
- Valsartan 80 mg daily, titrate to 320 mg daily
Critical consideration: Titrate to full dose before adding additional agents 1, 2
Step 2: Add Dihydropyridine Calcium Channel Blocker
After maximizing ACE inhibitor/ARB dose:
- Add a long-acting dihydropyridine CCB 1, 2, 3
- Non-dihydropyridine CCBs (diltiazem, verapamil) can reduce albuminuria but should not replace ACE inhibitors/ARBs 2
Common doses:
- Amlodipine 5 mg daily, titrate to 10 mg daily
- Nifedipine extended-release 30 mg daily, titrate to 90 mg daily
Important caveat: Dihydropyridine CCBs should never be used as monotherapy in proteinuric CKD patients—always combine with a RAAS blocker 2
Step 3: Add Thiazide-Like Diuretic
After maximizing ACE inhibitor/ARB and CCB:
- Add a thiazide-like diuretic 1, 3
- Thiazide-like diuretics (chlorthalidone, indapamide) are preferred over hydrochlorothiazide 3
Dosing considerations:
- Chlorthalidone 12.5-25 mg daily (effective even in stage 4 CKD with eGFR 15-30 mL/min/1.73 m²) 3
- Indapamide 1.25-2.5 mg daily
- Loop diuretics (furosemide 40-80 mg daily or higher) are needed when eGFR <30 mL/min/1.73 m² or with volume overload 4
Step 4: Add Mineralocorticoid Receptor Antagonist for Resistant Hypertension
For treatment-resistant hypertension (BP uncontrolled on 3 drugs including a diuretic):
- Add spironolactone 25 mg daily, titrate to 50 mg daily 1, 3
- Alternative agents if spironolactone not tolerated: amiloride, doxazosin, eplerenone, clonidine, or beta-blocker 1
Critical monitoring requirement: Risk of hyperkalemia restricts broad use in moderate-to-advanced CKD 3
- Check potassium and creatinine within 1 week of initiation
- Consider chlorthalidone co-administration to mitigate hyperkalemia risk 3
Step 5: Emerging Agents
SGLT2 inhibitors are now recommended:
- For hypertensive CKD patients with eGFR >20 mL/min/1.73 m² to improve outcomes 1
- These provide modest BP-lowering (3-5 mmHg systolic) with significant cardiovascular and renal protection 5
- Examples: Dapagliflozin 10 mg daily, empagliflozin 10 mg daily
Special Populations
Kidney Transplant Recipients
Target BP <130/80 mmHg regardless of albuminuria level 1
- Choose BP-lowering agents considering time post-transplant, calcineurin inhibitor use, and persistent albuminuria 1
Elderly and Frail Patients
For patients <85 years who are not moderately-to-severely frail:
- Follow same guidelines as younger patients if treatment is well tolerated 1
For patients ≥85 years:
Essential safety measure: Test for orthostatic hypotension before starting or intensifying BP medications (measure BP after 5 minutes sitting/lying, then at 1 and/or 3 minutes after standing) 1
Black Patients
Modified approach for Black patients with CKD:
- Start with low-dose ARB plus dihydropyridine CCB or CCB plus thiazide-like diuretic 1
- Titrate to full dose, then add the missing component (diuretic or ARB/ACE inhibitor) 1
Critical Pitfalls to Avoid
Do not discontinue ACE inhibitors/ARBs during volume optimization unless hemodynamically unstable 4
- Volume optimization typically improves tolerance of these medications
Do not use ACE inhibitor and ARB combination therapy:
- This increases adverse events without additional benefit (general medical knowledge)
Monitor for acute kidney injury:
- Expect modest creatinine increases (up to 30%) after starting ACE inhibitors/ARBs—this is acceptable 2
- Discontinue only if creatinine rises >30% or hyperkalemia develops despite management
Avoid aggressive single-session fluid removal in dialysis patients:
- This causes intradialytic hypotension and accelerates loss of residual kidney function 4
- Target gradual ultrafiltration over multiple sessions 4
Do not ignore dietary sodium restriction:
- Restrict sodium to <2 grams daily (<90 mmol/day) as the cornerstone of volume management 4, 3
- Sodium restriction improves BP control, especially with RAAS blockade 3
Monitoring Requirements
Regular assessment should include: