Can losartan (angiotensin II receptor antagonist) be used in patients with end-stage renal disease (ESRD)?

Can Losartan Be Used in End-Stage Kidney Disease?

Losartan can be used in end-stage renal disease (ESRD) without dose adjustment, as its pharmacokinetics are minimally altered in dialysis-dependent patients, though careful monitoring for hyperkalemia and hemodynamic instability is essential. 1, 2

Pharmacokinetic Evidence Supporting Use in ESRD

• Losartan does not require dose adjustment in ESRD patients, including those on hemodialysis, as pharmacokinetic studies demonstrate that both losartan and its active metabolite E-3174 maintain similar drug levels compared to patients with normal renal function. 2

• Neither losartan nor E-3174 are removed by dialysis, eliminating the need for post-dialysis supplementation. 2

• The FDA label confirms that losartan is indicated for diabetic nephropathy with elevated serum creatinine and proteinuria, and it reduces progression to ESRD (need for dialysis or renal transplantation). 1

Guideline Recommendations for ESRD

• For patients with ESRD (CrCl <15 mL/min or dialysis-dependent), individualized decision-making with well-managed vitamin K antagonists is preferred for anticoagulation contexts, though this does not preclude losartan use for blood pressure or renal protection. 3

• The European Heart Journal recommends losartan 50-100 mg/day for hypertension or renal failure in type 2 diabetes with microalbuminuria, with regular monitoring of electrolyte balance and serum creatinine. 3

Critical Monitoring Requirements

Monitor serum potassium and creatinine within 2-4 weeks after initiation or dose increase, as hyperkalemia is the primary risk in ESRD patients on losartan. 4, 1

• Halt losartan immediately if potassium rises to ≥6.0 mmol/L or if creatinine rises to >310 μmol/L (3.5 mg/dL). 4

• Halve the dose if potassium rises to >5.5 mmol/L or creatinine rises to >220 μmol/L (2.5 mg/dL). 4

Absolute Contraindications and High-Risk Scenarios

Avoid losartan in ESRD patients with bilateral renal artery stenosis or unilateral stenosis in a solitary kidney, as angiotensin II blockade can cause critical drops in glomerular filtration pressure and acute anuria. 5, 6

• Case reports document transient anuria episodes lasting 8-10 hours in patients with renovascular disease and activated renin-angiotensin systems, particularly when combined with volume depletion from diuretics. 5

Temporarily suspend losartan during intercurrent illness, planned IV radiocontrast administration, bowel preparation for colonoscopy, or prior to major surgery to prevent acute kidney injury. 4

Combination Therapy Warnings

Never combine losartan with ACE inhibitors and/or direct renin inhibitors in ESRD patients, as dual RAAS blockade increases adverse events (hyperkalemia, acute kidney injury) without additional benefit. 4, 1

• The NEPHRON-D trial demonstrated increased acute kidney injury and hyperkalemia with combined losartan and lisinopril, with no mortality or cardiovascular benefit. 3

Renal Benefits Despite ESRD

• Losartan administration in ESRD patients resulted in declined plasma uric acid levels despite absent residual renal function, suggesting extrarenal benefits. 2

• The RENAAL trial showed losartan reduced progression to ESRD by 28% (P=0.002) and reduced doubling of serum creatinine by 25% (P=0.006) in type 2 diabetic nephropathy patients. 7, 8

Practical Algorithm for ESRD Patients

1. Confirm absence of bilateral renal artery stenosis before initiating losartan 5, 6
2. Check baseline potassium and creatinine 1
3. Start standard dose (50-100 mg daily) without reduction 2
4. Recheck potassium and creatinine within 1-2 weeks 4
5. Adjust or discontinue based on monitoring thresholds above 4
6. Avoid concomitant ACE inhibitors, aldosterone antagonists, or NSAIDs 4, 1

Common Pitfalls

• Do not assume losartan is safer than ACE inhibitors in ESRD—both carry similar renal toxicity risks, with identical 10.5% incidence of renal dysfunction in the ELITE trial. 6

• Volume depletion dramatically increases risk—correct volume or salt depletion prior to losartan administration, especially in patients on high-dose diuretics. 1, 5

• Concomitant antiplatelet therapy substantially elevates bleeding risk in ESRD patients requiring careful consideration. 3