What are the guidelines for using Losartan (angiotensin II receptor blocker) in patients with kidney failure, specifically those with chronic kidney disease (CKD) or end-stage renal disease (ESRD)?

Use of Losartan in Kidney Failure

Continue losartan in patients with chronic kidney disease even when eGFR falls below 30 ml/min/1.73 m², and only consider dose reduction or discontinuation when eGFR drops below 15 ml/min/1.73 m² in the presence of symptomatic hypotension, uncontrolled hyperkalemia despite medical management, or to reduce uremic symptoms. 1

Indications for Losartan in CKD

The 2024 KDIGO guidelines provide clear direction on when to initiate and continue ARBs like losartan:

• Start losartan for CKD patients with severely increased albuminuria (A3) without diabetes (Grade 1B recommendation) 1
• Start losartan for CKD patients with moderately-to-severely increased albuminuria (A2-A3) with diabetes (Grade 1B recommendation) 1
• Consider losartan for CKD patients with moderately increased albuminuria (A2) without diabetes (Grade 2C recommendation) 1
• Losartan may also be initiated for specific indications such as hypertension or heart failure with reduced ejection fraction, even in patients with normal to mildly increased albuminuria 1

Continuation Through Advanced CKD Stages

The most critical practice point: Continue losartan even when eGFR falls below 30 ml/min/1.73 m². 1 This represents a paradigm shift from older practices that routinely discontinued ARBs at lower GFR thresholds. The renoprotective and cardiovascular benefits persist in advanced CKD stages. 1

Dosing Considerations in Kidney Failure

• Use the highest approved tolerated dose to achieve proven benefits from clinical trials 1
• No routine dose adjustment is required based solely on renal impairment, unless the patient is also volume depleted 2
• Pharmacokinetic studies demonstrate that losartan and its active metabolite E-3174 are minimally altered in end-stage renal disease, and the drug is not dialyzable 3
• Standard dosing of 50-100 mg daily can be maintained in most patients with advanced CKD 3

When to Consider Dose Reduction or Discontinuation

Only reduce dose or discontinue losartan in advanced kidney failure (eGFR <15 ml/min/1.73 m²) under these specific circumstances: 1

• Symptomatic hypotension that cannot be managed by volume optimization
• Uncontrolled hyperkalemia (typically >5.5-6.0 mEq/L) despite medical treatment with potassium binders or dietary restriction 1, 2
• To reduce uremic symptoms in patients approaching or on dialysis
• Serum creatinine rise >30% within 4 weeks of initiation or dose increase 1

Critical Monitoring Protocol

Check blood pressure, serum creatinine, and serum potassium within 2-4 weeks of initiation or any dose increase 1

• An initial creatinine rise of 10-20% is expected and hemodynamic in nature, not indicative of kidney injury 4
• Continue therapy unless creatinine rises by more than 30% within 4 weeks 1
• Hyperkalemia can often be managed with potassium-lowering measures rather than stopping losartan 1

Management of Hyperkalemia Without Stopping Losartan

Prioritize potassium management strategies before discontinuing losartan: 1

• Dietary potassium restriction
• Discontinue potassium supplements and potassium-sparing diuretics 2
• Use potassium binders (patiromer, sodium zirconium cyclosilicate)
• Optimize volume status and metabolic acidosis
• Only reduce losartan dose if potassium remains >5.5 mEq/L despite these measures 4

Absolute Contraindications and High-Risk Situations

Avoid losartan in these specific scenarios: 1, 2

• Bilateral renal artery stenosis or unilateral stenosis in a solitary kidney 2, 5
• Pregnancy (second and third trimesters) 2
• Combination with ACE inhibitors, other ARBs, or direct renin inhibitors - this increases hyperkalemia and acute kidney injury risk without additional benefit 1, 2
• Active acute kidney injury - temporarily discontinue until GFR stabilizes 6

The VA NEPHRON-D trial definitively showed that combining losartan with an ACE inhibitor (lisinopril) in diabetic nephropathy increased hyperkalemia and acute kidney injury without improving outcomes. 2

Special Considerations for Dialysis Patients

• No post-dialysis supplementation is required because losartan and E-3174 are not dialyzable 3
• Losartan may be continued in patients on maintenance dialysis if blood pressure control or residual renal function preservation is needed 3
• The uric acid-lowering effect of losartan persists even without residual renal function 3

Temporary Suspension Scenarios

Consider temporarily holding losartan during: 4, 6

• Intercurrent illness with volume depletion
• Planned IV radiocontrast administration
• Bowel preparation prior to colonoscopy
• Major surgery
• Critical medical illness

Resume losartan after volume status is optimized and acute illness resolves, with repeat monitoring of renal function and potassium within 1 week. 6

Common Pitfalls to Avoid

• Do not routinely discontinue losartan when eGFR falls below 30 ml/min/1.73 m² - this outdated practice removes renoprotective benefits 1
• Do not combine with ACE inhibitors - dual RAS blockade increases harm 1, 2
• Do not stop losartan for mild hyperkalemia (5.0-5.5 mEq/L) without first attempting potassium-lowering strategies 1
• Do not assume losartan is safer than ACE inhibitors in terms of renal toxicity - they have similar risk profiles 5
• Do not use reduced doses without clinical indication - higher doses provide greater renoprotection 1

Alternative ARB Considerations

While losartan is effective, telmisartan may be preferred in end-stage CKD due to superior renoprotective properties, higher receptor affinity, longer half-life, and once-daily dosing that improves adherence. 7, 8 However, losartan remains an appropriate and well-studied option with established efficacy in diabetic nephropathy. 8