How to use Losartan (Losartan) in a patient with severe Chronic Kidney Disease (CKD)?

Losartan Use in Severe Chronic Kidney Disease (GFR Category G3b)

Losartan can be safely used in patients with GFR category G3b (eGFR 30-44 mL/min/1.73 m²) without dose adjustment, provided the patient is not volume depleted and does not have bilateral renal artery stenosis or a solitary kidney with stenosis. 1

Dosing and Initiation

• No dose adjustment is required for losartan in patients with renal impairment, including G3b CKD, unless the patient is also volume depleted 1
• Standard dosing remains 25-100 mg once daily 2, 3
• Start with 25 mg daily if the patient has any degree of volume depletion (e.g., concurrent high-dose diuretic use) to avoid symptomatic hypotension 1
• For normotensive patients with proteinuric CKD, losartan 50 mg daily has demonstrated effective renoprotection without causing hypotension 3

Critical Contraindications and Precautions

Absolute Contraindications

• Pregnancy (second and third trimesters): Discontinue immediately if pregnancy is detected due to fetal toxicity, including renal failure, oligohydramnios, and death 1
• Bilateral renal artery stenosis or stenosis in a solitary kidney: Can cause acute anuria and complete renal failure 4

Volume Status Assessment (Essential Before Initiation)

• Correct volume or salt depletion prior to starting losartan in patients on high-dose diuretics, those with heart failure, or any activated renin-angiotensin system 1
• Patients with severe heart failure combined with aggressive diuretic therapy are at particularly high risk for acute renal failure when losartan is initiated 4

Monitoring Requirements

Initial Monitoring (Within 1 Week of Starting)

• Serum creatinine and eGFR: Monitor for acute decline in renal function 1
• Serum potassium: Check for hyperkalemia, particularly if baseline potassium is elevated 1
• Blood pressure: Assess for symptomatic hypotension 1

Acceptable Changes vs. Red Flags

• An increase in serum creatinine of 10-20% is acceptable and does not require discontinuation 5
• Discontinue or withhold losartan if:
  • Clinically significant decrease in renal function occurs (>30% rise in creatinine) 1
  • Serum potassium exceeds 5.5 mEq/L 5, 1
  • Symptomatic hypotension develops 1

Ongoing Monitoring

• Monitor renal function and potassium periodically throughout treatment 1
• More frequent monitoring is warranted in patients with progressive CKD or those on multiple medications affecting potassium 1

Renoprotective Benefits in G3b CKD

• Losartan reduces proteinuria by approximately 24% independent of blood pressure reduction in patients with proteinuric CKD 2
• In normotensive patients with stage 3 CKD, losartan 50 mg daily stabilized eGFR over 12 months while placebo resulted in significant eGFR decline (44.8 to 44.1 vs. 44.5 to 39.1 mL/min/1.73 m²) 3
• The antiproteinuric effect is evident in both patients with proteinuria <2 g/day and ≥2 g/day 2

Combination Therapy Considerations

Adding Hydrochlorothiazide

• Losartan 50 mg plus hydrochlorothiazide 12.5 mg provides superior proteinuria reduction compared to losartan 100 mg alone in stage 3 CKD, even when blood pressures are equivalent 6, 7
• This combination reduces the urinary protein-to-creatinine ratio more effectively through mechanisms independent of blood pressure lowering 7
• The combination is particularly effective in diabetic patients with stage 3 CKD 6

Medications to Avoid

• Never combine losartan with ACE inhibitors or direct renin inhibitors: Substantially increases risk of hyperkalemia, hypotension, and acute renal failure [5, @29@]
• Avoid potassium supplements and potassium-sparing diuretics when using losartan due to hyperkalemia risk 5, 1

Management During Acute Illness

Temporary Discontinuation Scenarios

• Suspend losartan during high-risk periods including:
  • Intercurrent acute illness with volume depletion 5
  • Planned IV radiocontrast administration 5
  • Bowel preparation prior to colonoscopy 5
  • Major surgery 5

Reintroduction After Acute Kidney Injury

• Wait for GFR stabilization and volume status optimization before restarting 5
• Ensure mean arterial pressure >65 mm Hg to avoid symptomatic hypotension 5
• Confirm serum potassium <5.5 mEq/L before reintroduction 5
• Start with lower doses and monitor renal function and potassium within 1 week 5

Special Populations

Elderly Patients (≥65 Years)

• No dose adjustment required based on age alone 1
• Greater sensitivity to hypotension may occur; monitor closely 1

Black Patients

• The LIFE study showed losartan was less effective than atenolol for cardiovascular outcomes specifically in Black patients with hypertension and left ventricular hypertrophy 1
• This finding does not apply to renoprotection in CKD, where losartan remains beneficial regardless of race 2, 3

Hepatic Impairment

• Start with 25 mg daily in patients with mild-to-moderate hepatic impairment due to 5-fold increase in losartan plasma concentrations 1

Common Pitfalls to Avoid

1. Initiating losartan in volume-depleted patients without first correcting volume status leads to acute hypotension and potential renal failure 1, 4
2. Failing to check for renal artery stenosis in high-risk patients (elderly, atherosclerotic disease, flash pulmonary edema) before starting losartan can result in catastrophic anuria 4
3. Permanently discontinuing losartan after AKI recovery increases mortality and cardiovascular events; reintroduce once stable 5
4. Not monitoring potassium within the first week can miss dangerous hyperkalemia 1
5. Combining with other RAAS inhibitors dramatically increases adverse event risk without additional benefit [5, @29@]