What is the best Angiotensin II Receptor Blocker (ARB) for a 70-year-old patient with a high urine albumin to creatinine ratio (indicative of proteinuria)?

Best ARB for a 70-Year-Old with High Urine Albumin/Creatinine Ratio

Losartan is the most appropriate ARB for a 70-year-old patient with a high urine albumin-to-creatinine ratio due to its proven efficacy in reducing proteinuria and slowing progression of kidney disease in this population. 1

Rationale for ARB Selection

• ARBs are strongly recommended as first-line therapy for patients with elevated urine albumin-to-creatinine ratio (≥300 mg/g creatinine) and recommended for those with moderately elevated levels (30-299 mg/g creatinine) 2
• Losartan specifically has FDA approval for "treatment of diabetic nephropathy with elevated serum creatinine and proteinuria" and has been shown to reduce the rate of progression of nephropathy 1
• In the RENAAL study, losartan demonstrated a 16.1% risk reduction in the primary composite endpoint (doubling of serum creatinine, end-stage renal disease, or death) compared to placebo 1
• Losartan significantly reduced proteinuria by an average of 34%, with effects evident within 3 months of starting therapy 1
• Losartan significantly reduced the rate of decline in glomerular filtration rate by 13% compared to placebo 1

Dosing and Monitoring Recommendations

• Start with losartan 50 mg once daily 1
• Titrate to 100 mg once daily if blood pressure goal is not achieved (in the RENAAL study, 72% of patients received the 100 mg dose) 1
• Monitor serum creatinine/eGFR and potassium levels within 7-14 days after initiation and at least annually 2
• A temporary increase in serum creatinine up to 30% is acceptable and not a reason to discontinue therapy 2
• Consider stopping losartan only if kidney function continues to worsen or if refractory hyperkalemia develops 2

Comparative Efficacy of ARBs

• While several ARBs (losartan, irbesartan, valsartan, candesartan) have demonstrated efficacy in reducing proteinuria 3, losartan has the most robust evidence in patients with elevated albumin-to-creatinine ratio 1
• Some studies suggest olmesartan may have greater antiproteinuric effects than other ARBs in non-diabetic CKD 4, but losartan has stronger evidence specifically for patients with elevated albumin-to-creatinine ratio 1
• The LIFE study showed losartan reduced albuminuria by approximately 33% compared to 15% with atenolol (p<0.001) 5

Additional Considerations

• If blood pressure remains uncontrolled on maximum-dose losartan, consider adding a thiazide-like diuretic rather than another class of antihypertensive 2, 6
• The combination of losartan with hydrochlorothiazide has shown greater reduction in proteinuria than losartan alone, independent of blood pressure effects 6
• Never combine an ARB with an ACE inhibitor or direct renin inhibitor due to increased risk of adverse effects without added benefit 2
• For patients with resistant hypertension on three medications including a diuretic, consider adding a mineralocorticoid receptor antagonist, but monitor carefully for hyperkalemia 2

Monitoring for Efficacy and Safety

• Regularly monitor urine albumin-to-creatinine ratio to assess treatment response 2
• Counsel the patient to temporarily hold losartan during periods of volume depletion (e.g., acute illness with vomiting/diarrhea) 2
• Target blood pressure should be <130/80 mmHg for most patients with diabetes and hypertension 2
• If the patient has diabetes, continue monitoring for progression of diabetic kidney disease with annual urine albumin-to-creatinine ratio and eGFR measurements 2