What is the first-line treatment for a patient with chronic kidney disease (CKD) and uncontrolled hypertension?

First-Line Treatment for Hypertension in Chronic Kidney Disease

For patients with CKD and uncontrolled hypertension, ACE inhibitors or ARBs should be initiated as first-line therapy, titrated to the highest tolerated dose, with a target blood pressure of <130/80 mmHg using standardized office measurement. 1

Blood Pressure Target

• Target systolic BP <120 mmHg when tolerated using standardized office measurement, with an acceptable alternative range of 130-139 mmHg systolic. 1, 2
• For patients aged 18-49 years with CKD stages G1-G2 and BP >130/85 mmHg, target home BP of ≤110/75 mmHg if tolerated. 1
• All age groups with CKD should aim for <140/90 mmHg at minimum. 1

First-Line Pharmacological Therapy

ACE inhibitors or ARBs are the mandatory first-line agents for all CKD patients with hypertension, particularly those with albuminuria. 1

• Administer at the highest approved dose that is tolerated (e.g., lisinopril up to 40 mg daily, losartan up to 100 mg daily), as proven benefits in clinical trials were achieved at these target doses. 1, 3, 4
• For CKD patients with diabetes and severely increased albuminuria (stages G1-G4, A2-A3), RAS inhibition is strongly recommended. 1
• Even in CKD patients without albuminuria, RAS inhibitors are reasonable first-line therapy. 1

Race-Specific Considerations

• In Black patients with CKD, thiazide-type diuretics or calcium channel blockers may be considered as initial therapy for BP control. 1
• However, if a Black patient with CKD has proteinuria and achieves BP control with a single agent, that agent should be an ACE inhibitor or ARB. 1
• White patients can initiate therapy with ACE inhibitor, ARB, thiazide-type diuretic, or calcium channel blocker. 1

Critical Monitoring Parameters

Check serum creatinine and potassium within 2-4 weeks of initiating or increasing the dose of ACE inhibitors or ARBs. 1, 2, 5

• Continue ACE inhibitor/ARB therapy unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase. 1, 2, 5
• A creatinine increase ≤30% reflects hemodynamic changes and does not indicate harm. 1, 2
• Expect a small increase in serum potassium (approximately 0.1 mEq/L on average), with about 15% of patients experiencing increases >0.5 mEq/L. 3

Second-Line and Add-On Therapy

When BP remains uncontrolled on ACE inhibitor or ARB monotherapy:

• Add a long-acting dihydropyridine calcium channel blocker (amlodipine, nifedipine) as second-line therapy. 1, 2, 6
• Add a thiazide-type diuretic as third-line therapy for patients with eGFR ≥30 mL/min/1.73 m². 1, 6
• Switch to loop diuretics when eGFR <30 mL/min/1.73 m² or serum creatinine >2.0 mg/dL, as thiazides become ineffective. 2, 7
• For treatment-resistant hypertension requiring ≥3 drugs, consider adding spironolactone, but monitor closely for hyperkalemia. 1, 7

Management of Hyperkalemia

Hyperkalemia associated with ACE inhibitor or ARB use should be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping the RAS inhibitor. 1, 2, 5

• Strategies include dietary potassium restriction, adding loop diuretics, or using potassium binders. 1
• Only reduce dose or discontinue ACE inhibitor/ARB if hyperkalemia remains uncontrolled despite medical treatment. 1, 2

Critical Contraindications

Never combine ACE inhibitor + ARB + direct renin inhibitor, as this triple combination increases adverse events without benefit. 1, 2, 5

• Dual RAS inhibition (ACE inhibitor + ARB) is also not recommended due to increased risk of hyperkalemia, hypotension, and acute kidney injury. 1, 5

When to Continue or Discontinue RAS Inhibitors

Continue ACE inhibitor or ARB even when eGFR falls below 30 mL/min/1.73 m². 2, 5

• Only consider dose reduction or discontinuation at eGFR <15 mL/min/1.73 m² (CKD Stage 5) if:
  • Symptomatic hypotension develops 1, 2
  • Uncontrolled hyperkalemia persists despite medical treatment 1, 2
  • Uremic symptoms require management 1, 2

Non-Pharmacological Management

Restrict dietary sodium to <2.0-2.3 g/day (<90 mmol/day) to enhance diuretic efficacy and BP control. 2, 7, 8

• Sodium restriction improves BP control, especially in patients treated with RAS inhibitors. 7, 8
• Lifestyle modifications including weight loss, exercise, and smoking cessation should complement pharmacotherapy. 1, 9

Common Pitfalls to Avoid

• Do not stop ACE inhibitor/ARB for modest creatinine increases up to 30%. 1, 2, 5
• Do not use thiazide diuretics as monotherapy in advanced CKD (eGFR <30 mL/min/1.73 m²); switch to loop diuretics. 2, 7
• Do not discontinue medications just because BP falls below target without adverse effects. 1
• Do not use non-dihydropyridine calcium channel blockers as monotherapy in proteinuric CKD patients; always combine with RAS blockade. 6, 10