How to manage hypertension in patients with Chronic Kidney Disease (CKD)?

Management of Hypertension in CKD Patients

Target a systolic blood pressure <120 mm Hg using standardized office BP measurement in adults with CKD when tolerated, and initiate ACE inhibitors or ARBs as first-line therapy for patients with albuminuria. 1

Blood Pressure Measurement and Targets

Measurement Technique

• Use standardized office BP measurement rather than routine casual measurements, preferably with automated oscillometric devices (attended or unattended AOBP) 1
• Supplement office readings with ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) to identify masked hypertension, white coat hypertension, and abnormal nocturnal dipping patterns common in CKD 1, 2
• Critical pitfall: Applying the <120 mm Hg target to non-standardized BP measurements is potentially hazardous 1

BP Targets Based on Albuminuria Status

For patients WITHOUT diabetes:

• Minimal albuminuria (<30 mg/24h): Target BP <140/90 mm Hg 1
• Moderate albuminuria (30-300 mg/24h): Target BP <130/80 mm Hg 1
• Severe albuminuria (>300 mg/24h): Target BP <130/80 mm Hg 1

For patients WITH diabetes:

• Minimal albuminuria (<30 mg/24h): Target BP <140/90 mm Hg 1
• Any albuminuria (≥30 mg/24h): Target BP <130/80 mm Hg 1

However, the 2021 KDIGO guideline supersedes these recommendations with a more aggressive target of systolic BP <120 mm Hg for all adults with CKD when tolerated, regardless of albuminuria or diabetes status 1, 3

Special Populations

• Kidney transplant recipients: Target BP <130/80 mm Hg regardless of albuminuria level 1
• Elderly patients or those with symptomatic postural hypotension: Less intensive BP-lowering therapy is reasonable, potentially targeting <140/80 mm Hg 1, 3
• Patients with very limited life expectancy: Less aggressive targets are appropriate 1

Pharmacological Management Algorithm

First-Line Therapy: RAS Inhibition

ACE inhibitors or ARBs are the cornerstone of treatment in CKD with albuminuria:

• Severe albuminuria (>300 mg/24h or ACR >300 mg/g):

  • Strong recommendation (1B) to use ACE-I or ARB in both diabetic and non-diabetic patients 1
  • This applies to CKD stages G1-G4 1

• Moderate albuminuria (30-300 mg/24h or ACR 30-300 mg/g):

  • Recommended (1B for diabetes, 2C-2D for non-diabetic) to use ACE-I or ARB 1

• Minimal or no albuminuria (<30 mg/24h):

  • ACE-I or ARB may be reasonable but not specifically mandated 1
  • Target standard BP <140/90 mm Hg with any appropriate agent 1

Monitoring after RAS inhibitor initiation:

• Check BP, serum creatinine, and potassium within 2-4 weeks of starting or dose escalation 3
• Continue therapy unless: creatinine rises >30% within 4 weeks, symptomatic hypotension occurs, uncontrolled hyperkalemia develops, or eGFR <15 mL/min/1.73 m² with uremic symptoms 3

Second-Line Therapy: Calcium Channel Blockers

• Add a long-acting dihydropyridine calcium channel blocker (e.g., amlodipine) if BP remains uncontrolled on maximally tolerated RAS inhibitor 3, 4
• Non-dihydropyridine CCBs (diltiazem, verapamil) reduce albuminuria but should not replace RAS inhibitors 4
• Never use dihydropyridine CCBs as monotherapy in proteinuric CKD; always combine with RAS blocker 4

Third-Line Therapy: Diuretics

• Add thiazide-like diuretic (chlorthalidone or indapamide) if eGFR ≥30 mL/min/1.73 m² 3, 5
• Switch to loop diuretic (furosemide, torsemide) if eGFR <30 mL/min/1.73 m² 3, 5
• Chlorthalidone remains effective even in stage 4 CKD (eGFR 15-30) based on the CLICK trial 5

Treatment-Resistant Hypertension (Fourth-Line)

• Add spironolactone (mineralocorticoid receptor antagonist) for resistant hypertension 5
• Critical monitoring: Risk of hyperkalemia increases substantially in moderate-to-advanced CKD 5
• Chlorthalidone can mitigate hyperkalemia risk when used with spironolactone, but requires careful BP and renal function monitoring 5
• Novel non-steroidal MRAs (ocedurenone) may offer safer alternatives in the future 5

Absolute Contraindications

Never combine ACE inhibitor + ARB + direct renin inhibitor in CKD patients due to increased risk of adverse outcomes without benefit 3, 6

Lifestyle Modifications

Sodium Restriction

• Target sodium intake <2 g/day (equivalent to <90 mmol/day or <5 g sodium chloride/day) 1
• Sodium restriction enhances effectiveness of RAS inhibitors and improves BP control 1, 3, 7
• Exception: Not appropriate for patients with salt-wasting nephropathy 1

Physical Activity

• Recommend moderate-intensity physical activity for cumulative 150 minutes per week or to level compatible with cardiovascular and physical tolerance 1
• Modify intensity based on cardiorespiratory fitness, physical limitations, cognitive function, and fall risk 1
• Health benefits occur even if activity falls below general population targets 1

Dietary Considerations

• DASH-type diet or potassium-rich salt substitutes may not be appropriate in advanced CKD (eGFR <30) or conditions causing impaired potassium excretion due to hyperkalemia risk 1
• Encourage smoking cessation and moderate alcohol consumption 1

Monitoring and Follow-Up

Regular Assessments

• Inquire about postural dizziness and check for orthostatic hypotension at every visit when treating with BP-lowering drugs 1
• Monitor serum creatinine and potassium 2-4 weeks after any RAS inhibitor dose change 3
• Use ABPM or HBPM to detect non-dipping patterns (common in CKD) associated with worse cardiovascular and renal prognosis 2, 8

Treatment Individualization

• Consider age, coexistent cardiovascular disease, comorbidities, CKD progression risk, diabetic retinopathy presence, and treatment tolerance when selecting agents and targets 1
• For kidney transplant recipients, factor in time post-transplant, calcineurin inhibitor use, persistent albuminuria, and comorbidities 1

Common Pitfalls to Avoid

• Do not use casual office BP measurements to guide intensive BP targets; standardized measurement is essential 1
• Do not abruptly discontinue all antihypertensives in hypotensive patients; use stepwise approach 6
• Do not continue RAS inhibitors if creatinine rises >30% within 4 weeks unless due to volume depletion 3
• Do not overlook sodium restriction—it is frequently neglected but critical for BP control in CKD 1, 7
• Do not use thiazide diuretics alone when eGFR <30 mL/min/1.73 m²; switch to loop diuretics 3, 5