Can losartan (angiotensin II receptor antagonist) be given to a patient with stage 4 Chronic Kidney Disease (CKD)?

Losartan Use in Stage 4 CKD

Losartan can be used in patients with stage 4 CKD, but only as a second-line agent if an ACE inhibitor is not tolerated, with careful monitoring of kidney function and potassium levels.

Rationale for RAAS Blockade in CKD

Angiotensin receptor blockers (ARBs) like losartan can provide benefits in CKD patients through several mechanisms:

• Reduction of intraglomerular pressure
• Reduction of proteinuria
• Slowing kidney disease progression
• Blood pressure control

Guidelines for ARB Use in Advanced CKD

According to the 2017 ACC/AHA Hypertension Guideline 1:

• In adults with hypertension and CKD stage 3 or higher with albuminuria (≥300 mg/d or ≥300 mg/g albumin-to-creatinine ratio):
  • ACE inhibitors are the preferred first-line agents (Class IIa, Level C-EO)
  • ARBs like losartan may be reasonable if an ACE inhibitor is not tolerated (Class IIb, Level C-EO)

Monitoring Requirements

When using losartan in stage 4 CKD:

1. Renal function monitoring:

   • Check serum creatinine and eGFR at baseline
   • Recheck within 1-2 weeks after initiation or dose changes
   • Monitor periodically thereafter
   • Consider discontinuation if clinically significant decrease in renal function occurs 2

2. Potassium monitoring:

   • Check serum potassium at baseline
   • Monitor periodically after initiation
   • Consider dose reduction or discontinuation if hyperkalemia develops 2

3. Blood pressure monitoring:

   • Target BP <130/80 mmHg as recommended for CKD patients 1
   • Monitor for hypotension, especially in volume-depleted patients

Dosing Considerations

• Start at a lower dose (25 mg daily) 3
• Titrate cautiously based on blood pressure response and kidney function
• Maximum dose of 100 mg daily may be used if tolerated 3
• Avoid combination with ACE inhibitors or aldosterone antagonists 3

Research Evidence

Research supports the use of losartan in advanced CKD:

• Losartan has been studied in patients with moderate to severe renal insufficiency (eGFR 10-29 mL/min/1.73m²) and was found to be effective in reducing blood pressure with stable renal function parameters 4

• In patients with proteinuric CKD and hypertension, losartan demonstrated renoprotective effects by reducing proteinuria by approximately 24%, independent of its blood pressure-lowering effects 5

Precautions and Contraindications

Exercise caution with losartan in stage 4 CKD patients with:

1. Volume or salt depletion - correct before administration 2
2. Bilateral renal artery stenosis - avoid use 6
3. Pregnancy - contraindicated 2
4. Concomitant medications that increase potassium 2

Clinical Algorithm for Losartan Use in Stage 4 CKD

1. First, determine if an ACE inhibitor has been tried:

   • If ACE inhibitor was tolerated without issues → continue ACE inhibitor
   • If ACE inhibitor caused cough or angioedema → consider losartan
   • If ACE inhibitor caused hyperkalemia or acute kidney injury → use caution with losartan as similar effects may occur 6

2. Before initiating losartan:

   • Check baseline kidney function (eGFR, creatinine)
   • Check baseline potassium level
   • Ensure patient is not volume depleted
   • Rule out bilateral renal artery stenosis

3. Initiation and titration:

   • Start with 25 mg daily
   • Monitor kidney function and potassium within 1-2 weeks
   • If tolerated, may increase to 50 mg daily after 2-4 weeks
   • Further titration to 100 mg daily if needed and tolerated

4. Ongoing monitoring:

   • Check kidney function and potassium every 1-3 months
   • Discontinue if serum creatinine increases >30% from baseline or if potassium >6.0 mEq/L

Conclusion

While losartan can be used in stage 4 CKD, it should be used as a second-line agent when ACE inhibitors cannot be tolerated. Close monitoring of kidney function and potassium levels is essential, and the benefits of blood pressure control and potential renoprotection must be weighed against the risks of further kidney function deterioration and hyperkalemia.