What is the recommended treatment for patients with chronic kidney disease (CKD) and uncontrolled hypertension?

Management of Hypertension in Chronic Kidney Disease

For patients with chronic kidney disease and uncontrolled hypertension, renin-angiotensin system inhibitors (ACEi or ARB) should be used as first-line therapy, with the addition of diuretics, particularly loop diuretics in advanced CKD, as part of a multi-drug regimen to achieve a target blood pressure of <130/80 mmHg.

First-Line Therapy

RAS Inhibitors (ACEi or ARB)

• Recommended as first-line therapy for all CKD patients with hypertension 1
• Particularly indicated in:
  • CKD with severely increased albuminuria (G1-G4, A3) without diabetes (strong recommendation) 1
  • CKD with moderately increased albuminuria (G1-G4, A2) without diabetes 1
  • CKD with moderately-to-severely increased albuminuria (G1-G4, A2 and A3) with diabetes 1
• Should be administered at the highest approved dose that is tolerated 1
• Continue even when eGFR falls below 30 ml/min per 1.73 m² 1

Diuretic Therapy

Loop Diuretics

• Particularly effective in advanced CKD (eGFR <30 ml/min/1.73m²) when thiazide diuretics lose effectiveness 2
• Furosemide dosing:
  • Initial dose: 20-80 mg once daily
  • Can be increased to 40-80 mg twice daily
  • In severe cases, can be titrated up to 600 mg/day 2
  • For hypertension: Usually 80 mg daily, divided into 40 mg twice daily 2

Additional Agents for Combination Therapy

Calcium Channel Blockers

• Dihydropyridine CCBs (e.g., amlodipine) are effective second-line agents 3, 4
• Should be used in combination with RAS inhibitors, not as monotherapy in proteinuric CKD 4

SGLT2 Inhibitors

• Recommended for CKD patients with:
  • Type 2 diabetes and eGFR ≥20 ml/min per 1.73 m² 1
  • eGFR ≥20 ml/min per 1.73 m² with urine ACR ≥200 mg/g 1
  • Heart failure, irrespective of albuminuria level 1

Mineralocorticoid Receptor Antagonists

• Consider non-steroidal MRAs for adults with T2D, eGFR >25 ml/min per 1.73 m², normal potassium, and persistent albuminuria despite maximum RASi dose 1
• Spironolactone is effective for resistant hypertension but requires careful monitoring for hyperkalemia 1, 3

Treatment Algorithm

1. Start with RASi (ACEi or ARB) at maximum tolerated dose

   • Monitor serum creatinine and potassium within 2-4 weeks of initiation 1
   • Continue unless creatinine rises >30% within 4 weeks 1

2. Add loop diuretic (e.g., furosemide) if BP remains uncontrolled or if volume overload is present

   • Start with 40 mg daily, titrate as needed up to 80 mg twice daily 2
   • For advanced CKD (eGFR <30 ml/min/1.73m²), higher doses may be required

3. Add dihydropyridine CCB if BP remains uncontrolled

   • Amlodipine is commonly used and well-tolerated

4. Consider SGLT2i if patient meets criteria (diabetes, significant albuminuria, or heart failure)

5. For resistant hypertension, consider adding:

   • Non-steroidal MRA if eGFR >25 ml/min/1.73m² 1
   • Spironolactone with careful monitoring of potassium 3

Blood Pressure Targets

• Target BP <130/80 mmHg for all CKD patients 1
• Standardized office BP measurement is essential for accurate assessment 1
• Consider home BP monitoring to confirm diagnosis and treatment response 5

Monitoring

• Check BP, serum creatinine, and potassium within 2-4 weeks after starting or increasing dose of RASi 1
• Continue RASi unless serum creatinine rises by more than 30% 1
• Monitor electrolytes more frequently in patients on multiple agents, especially when using MRAs 5

Important Cautions

• Avoid any combination of ACEi, ARB, and direct renin inhibitors 1
• Consider reducing dose or discontinuing RASi in cases of:
  • Symptomatic hypotension
  • Uncontrolled hyperkalemia despite treatment
  • Uremic symptoms in advanced kidney failure 1
• Hyperkalemia with RASi can often be managed without discontinuation 1

Loop diuretics are particularly important in the management of hypertension in advanced CKD, as they remain effective even at lower GFR levels when thiazide diuretics lose their efficacy 3, 6, 7.

Bold text represents the most important recommendation.