What is the recommended antihypertensive regimen for an adult with chronic kidney disease, including first‑line agents, target blood pressure, and subsequent add‑on therapy based on renal function and proteinuria?

Blood Pressure Medications for CKD Patients

For adults with CKD and hypertension, start with an ACE inhibitor or ARB as first-line therapy, with blood pressure targets and additional agents determined by the degree of proteinuria: <140/90 mmHg for minimal proteinuria (<30 mg/24h) and <130/80 mmHg for significant proteinuria (≥30 mg/24h). 1

Blood Pressure Targets Based on Proteinuria Status

Minimal or No Proteinuria (<30 mg/24h)

• Target BP <140/90 mmHg for both diabetic and non-diabetic CKD patients 1
• ACE inhibitor or ARB may be reasonable as first-line but is not mandatory in this population 1

Moderate Proteinuria (30-300 mg/24h)

• Target BP <130/80 mmHg for both diabetic and non-diabetic patients 1
• Start with ACE inhibitor or ARB (Grade 2D recommendation for non-diabetics; Grade 2D for diabetics) 1

Heavy Proteinuria (≥300 mg/24h)

• Target BP <130/80 mmHg for both diabetic and non-diabetic patients 1
• Mandatory use of ACE inhibitor or ARB (Grade 1B recommendation) 1
• This is the strongest evidence-based indication for RAS blockade in CKD 1

First-Line Agent Selection and Dosing

ACE Inhibitor or ARB

• Use the highest approved dose tolerated to achieve maximum antiproteinuric benefit, as trial benefits were demonstrated at these doses 1
• Choose ARB over ACE inhibitor in patients receiving mTORC1 inhibitors due to lower angioedema risk 1
• Monitor serum creatinine and potassium within 2-4 weeks of initiation or dose increase 1
• Accept up to 30% increase in serum creatinine within 4 weeks as an expected hemodynamic effect; only discontinue if rise exceeds 30% 1, 2

Add-On Therapy Algorithm

Second-Line: Diuretics

• Add a thiazide-like diuretic (chlorthalidone or indapamide preferred) if BP target not achieved with maximized RAS blockade 3, 4, 2
• Diuretics are particularly effective in salt-sensitive, hypervolemic CKD patients 5, 6

Third-Line: Calcium Channel Blockers

• Add a dihydropyridine CCB (amlodipine, nifedipine) for additional BP control, always in combination with RAS blockade—never as monotherapy in proteinuric patients 6
• Non-dihydropyridine CCBs (diltiazem, verapamil) reduce albuminuria and may be preferred in proteinuric disease 6

Fourth-Line: Mineralocorticoid Receptor Antagonists

• Add spironolactone 25-50 mg daily or eplerenone for resistant proteinuria despite RAS blocker plus diuretic 1, 3, 4
• Requires careful potassium monitoring, especially with eGFR <45 mL/min/1.73 m² 1

SGLT2 Inhibitors (Diabetic CKD)

• Add SGLT2 inhibitor (empagliflozin, canagliflozin, or dapagliflozin) for all diabetic CKD patients with proteinuria >300 mg/g, regardless of glycemic control 3, 4, 2
• Provides additive renoprotection to ARBs through complementary mechanisms 2
• Consider even in non-diabetic CKD based on emerging evidence 1

Critical Monitoring Parameters

Initial Monitoring (First 2-4 Weeks)

• Check serum creatinine, eGFR, and potassium within 2-4 weeks after starting or uptitrating RAS blockade 1, 2
• Monitor for orthostatic hypotension at every visit 1

Ongoing Monitoring

• Urine albumin-to-creatinine ratio every 3-6 months, targeting reduction to <300 mg/g or at least 30-50% reduction from baseline 3, 4, 2
• Continue monitoring potassium regularly, especially when using MRAs or in advanced CKD 1

When to Modify or Stop RAS Blockade

Continue Therapy Despite:

• Up to 30% increase in serum creatinine within 4 weeks of initiation 1, 2
• eGFR decline to <30 mL/min/1.73 m² or even <15 mL/min/1.73 m² 1, 2

Reduce Dose or Discontinue If:

• Serum creatinine rises >30% within 4 weeks 1
• Symptomatic hypotension despite dose adjustment 1
• Refractory hyperkalemia despite potassium-lowering measures 1
• Acute intercurrent illness with volume depletion (temporarily hold) 2

Critical Pitfalls to Avoid

Combination RAS Blockade

• Never combine ACE inhibitor + ARB + direct renin inhibitor (Grade 1B recommendation against) 1, 2
• Dual ACE inhibitor/ARB therapy increases harm without additional benefit 1

Lifestyle Modifications

• Restrict dietary sodium to <2 g/day (<90 mmol/day), which synergistically enhances antiproteinuric effects of RAS blockade 3, 4, 2
• Avoid NSAIDs, which counteract RAS blockade benefits 1

Special Populations

• Children with CKD: Start treatment when BP consistently >90th percentile; target ≤50th percentile using ACE inhibitor or ARB first-line 1
• Kidney transplant recipients: Target <130/80 mmHg using dihydropyridine CCB or ARB as first-line 1