What is the role of Losartan (Angiotensin II Receptor Antagonist) in End-Stage Renal Disease (ESRD)?

From the Guidelines

Losartan can be used in patients with end-stage renal disease (ESRD), but requires dose adjustment and careful monitoring, as evidenced by the RENAAL trial 1 and the KDIGO 2020 clinical practice guideline 1.

Key Considerations

• For ESRD patients on dialysis, the recommended starting dose is 25-50 mg once daily, which is lower than the typical starting dose for patients with normal kidney function.
• The maximum dose should generally not exceed 50 mg daily in ESRD.
• Losartan should be administered after dialysis sessions to prevent removal of the medication during treatment.
• Close monitoring of blood pressure, potassium levels, and renal function is essential, as ESRD patients are at higher risk for hyperkalemia and hypotension.

Mechanism and Benefits

• Despite kidney impairment, losartan may still provide cardiovascular protection and reduce proteinuria in ESRD patients who have residual renal function.
• The medication works by blocking angiotensin II receptors, reducing vasoconstriction and aldosterone secretion, as supported by the IRMA-2 and INNOVATION trials 1.
• This mechanism remains beneficial even in advanced kidney disease, though the renoprotective effects are less relevant once dialysis dependence occurs.

Potential Risks and Monitoring

• If hyperkalemia develops (potassium >5.5 mEq/L) or if significant hypotension occurs, dose reduction or discontinuation may be necessary.
• The KDIGO 2020 clinical practice guideline 1 suggests that ACEi and ARBs, including losartan, are generally well-tolerated, but may cause little or no difference in the occurrence of certain adverse events.

Summary of Evidence

• The RENAAL trial 1 demonstrated a 16% reduction in the incidence of doubling of serum creatinine, ESKD, and death with losartan compared to placebo.
• The KDIGO 2020 clinical practice guideline 1 updates the evidence on the use of ACEi and ARBs in patients with diabetes and CKD, supporting the use of these medications to reduce the progression of CKD.

From the FDA Drug Label

1. 3 Renal Function Deterioration Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on losartan. Monitor renal function periodically in these patients Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan [see DRUG INTERACTIONS (7.3) and USE IN SPECIFIC POPULATIONS (8.7)].

Losartan can be used in patients with End-Stage Renal Disease (ESRD), but with caution. The drug label warns of the potential for renal function deterioration, including acute renal failure, in patients with pre-existing renal disease.

• Monitoring of renal function is recommended in these patients.
• Withholding or discontinuing losartan may be necessary if a clinically significant decrease in renal function occurs. 2 and 2

From the Research

Losartan in ESRD

• Losartan is an angiotensin-II-receptor antagonist that has been shown to slow the progression of renal disease in patients with type 2 diabetes and nephropathy 3.
• The use of losartan in patients with end-stage renal disease (ESRD) may be beneficial in reducing the risk of cardiovascular morbidity and mortality, as it has been shown to reduce the incidence of a doubling of the serum creatinine concentration and end-stage renal disease 3.
• In patients with ESRD, controlling blood pressure is important to improve mortality, and losartan may be a useful agent in achieving this goal 4, 5.
• However, the management of blood pressure in ESRD is complicated by factors such as missed dialysis treatments, intradialytic changes in blood pressure, and medication removal with dialysis, and individualization of therapy is necessary 5.
• Angiotensin receptor blockers (ARBs), such as losartan, are reasonable first-line agents for most patients with ESRD, as they exert cardioprotective effects that are independent of blood pressure reduction 5.

Considerations for Use

• The decision to use losartan in patients with ESRD should be made on a case-by-case basis, taking into account the patient's comorbidities and individual needs 5.
• Losartan may be preferred in patients who are prone to develop intradialytic hypotension, as it is not removed with dialysis 5.
• The dosage of losartan may need to be adjusted in patients with ESRD, and thrice-weekly dosing after dialysis may be a useful regimen in nonadherent patients 5.