Losartan Use in Renal Impairment
Losartan is recommended for patients with impaired renal function, particularly those with diabetic nephropathy and proteinuria, as it provides significant renoprotection by slowing progression to end-stage renal disease, and no dose adjustment is necessary unless the patient is also volume depleted. 1
Primary Indications for Losartan in Renal Disease
For patients with type 2 diabetes, hypertension, and macroalbuminuria (proteinuria >300 mg/day), losartan is strongly recommended as it reduces the risk of doubling serum creatinine by 25%, progression to end-stage renal disease by 28%, and decreases proteinuria by 35% compared to placebo. 2, 3 The landmark RENAAL trial demonstrated these benefits over 3.4 years in patients who already had nephropathy with elevated creatinine levels. 2, 3
- ARBs like losartan are more effective than other antihypertensive drug classes (calcium channel blockers, beta-blockers, diuretics) in slowing GFR decline and preventing kidney failure in type 2 diabetic patients with macroalbuminuria. 2
- The renoprotective effect exceeds what would be expected from blood pressure lowering alone, indicating additional mechanisms beyond hemodynamic effects. 2, 3
- For non-diabetic CKD with severely increased albuminuria, losartan reduces risk of kidney failure and cardiovascular events (Grade 1B recommendation). 4
Dosing in Renal Impairment
No dose adjustment is required for patients with renal insufficiency unless they are also volume depleted. 1 The FDA label explicitly states this applies even when plasma concentrations of losartan and its active metabolite are elevated 50-90% in patients with mild (CrCl 50-74 mL/min) or moderate (CrCl 30-49 mL/min) renal insufficiency. 1
- Standard dosing is 50-100 mg once daily for renoprotection in diabetic nephropathy. 2, 3
- Start at lower doses (25 mg) in patients with GFR <45 mL/min/1.73 m² to minimize risk of acute hemodynamic changes. 4
- For normotensive patients with stage 3 CKD, even 50 mg daily provides effective renoprotection without causing hypotension. 5
- Neither losartan nor its active metabolite can be removed by hemodialysis. 1
Critical Monitoring Requirements
Check serum creatinine and potassium within 2-4 weeks after initiation or dose increase. 4, 1 This is essential because losartan can cause transient increases in creatinine due to hemodynamic changes in glomerular filtration.
When to Continue Therapy:
- Continue losartan if creatinine rises <30% within 4 weeks of initiation, as this represents expected hemodynamic adjustment rather than kidney injury. 4, 6
- Temporary GFR reduction after starting losartan is generally hemodynamic and not indicative of true kidney damage. 4
When to Adjust or Stop:
- Halve the dose if creatinine rises to >220 μmol/L (2.5 mg/dL). 4
- Stop immediately if creatinine rises to >310 μmol/L (3.5 mg/dL). 4
- Halve the dose if potassium rises to >5.5 mmol/L; stop if potassium ≥6.0 mmol/L. 4, 1
Specific Patient Populations
Advanced Renal Insufficiency (Creatinine >2.0 mg/dL):
Losartan retards progression even when initiated late in the course of renal disease. 7 A study of patients with baseline creatinine 2.2-5.5 mg/dL showed significant slowing of renal function decline with losartan 25-50 mg daily over 24 weeks. 7
Bilateral Renal Artery Stenosis:
Avoid losartan in patients with severe bilateral renal artery stenosis due to risk of acute renal failure, as these patients depend on angiotensin II-mediated efferent arteriolar constriction to maintain GFR. 4, 1
Volume-Depleted Patients:
Correct volume or salt depletion before starting losartan to prevent symptomatic hypotension in patients with activated renin-angiotensin systems (e.g., those on high-dose diuretics). 1
Important Contraindications and Precautions
Never combine losartan with ACE inhibitors, other ARBs, or direct renin inhibitors (Grade III: Harm recommendation), as dual RAS blockade increases risks of hyperkalemia, hypotension, and acute kidney injury without improving outcomes. 4, 8, 1
- Temporarily suspend losartan during intercurrent illness, IV radiocontrast administration, bowel preparation for colonoscopy, or before major surgery to prevent acute kidney injury during periods of hemodynamic stress. 4
- Monitor patients at particular risk: those with renal artery stenosis, severe heart failure, or chronic kidney disease whose renal function depends on RAS activity. 1
Additional Renal Benefits
The beneficial effect of losartan may be greater in patients with lower baseline GFR, possibly because the endpoint of doubling serum creatinine is reached more quickly, allowing detection of treatment effects. 2 Even in advanced CKD (stage 3), losartan 50 mg daily stabilizes estimated GFR while placebo groups show continued decline. 5