What is the best angiotensin‑II receptor blocker for a patient with hypertension, chronic kidney disease, and diabetes mellitus?

Best ARB for Hypertension in CKD and Diabetes

Losartan (50-100 mg daily) or irbesartan (150-300 mg daily) are the preferred ARBs for patients with hypertension, chronic kidney disease, and diabetes mellitus, with losartan being the only ARB with FDA-approved indication specifically for reducing hard renal endpoints (doubling of serum creatinine, ESRD, or death) in type 2 diabetic nephropathy. 1, 2

Evidence-Based Selection Between Losartan and Irbesartan

Both agents have Level 1 evidence from landmark trials demonstrating superior renoprotection compared to other antihypertensive classes:

Losartan (RENAAL Trial):

• Demonstrated 16% reduction in composite endpoint of doubling serum creatinine, ESRD, or death 1, 2
• Showed 25% reduction in sustained doubling of serum creatinine 1, 2
• Achieved 29% reduction in progression to ESRD 1, 2
• Reduced proteinuria by 35% independent of blood pressure lowering 3

Irbesartan (IDNT Trial):

• Demonstrated similar renoprotective efficacy in type 2 diabetic nephropathy with macroalbuminuria 3, 1
• Showed superiority over amlodipine and placebo in slowing GFR decline 3

The KDOQI guidelines explicitly state that either ARBs or ACE inhibitors can be used to treat diabetic kidney disease in hypertensive patients with type 2 diabetes and macroalbuminuria, with ARBs being more effective than other antihypertensive classes in slowing progression of kidney disease characterized by macroalbuminuria. 3

Practical Dosing Algorithm

Starting and Target Doses:

• Losartan: Start at 50 mg daily, titrate to 100 mg daily if blood pressure goal not achieved and medication tolerated 1, 2
• Irbesartan: Start at 150 mg daily, titrate to 300 mg daily based on clinical response 1

The renoprotective effect is dose-dependent, with higher doses providing greater protection against CKD progression. 1, 2

Essential Combination Therapy Considerations

Recommended Combinations:

• Add thiazide or loop diuretics to enhance efficacy, as 60-90% of patients in major ARB trials required concomitant diuretics 1, 2
• Most patients require 2-3 antihypertensive agents to reach target blood pressure <130/80 mmHg 1, 4

Absolutely Contraindicated Combinations:

• Never combine ARB + ACE inhibitor - this increases adverse events (hypotension, hyperkalemia, acute renal failure) without mortality benefit 1, 5, 2
• Avoid concomitant use with aliskiren in patients with diabetes 1

Monitoring Protocol

Timing and Parameters:

• Check serum creatinine, potassium, and blood pressure within 2-4 weeks of initiation or dose increase 1, 5
• Continue ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation or dose increase 1, 5
• Monitor for hyperkalemia, particularly in advanced CKD 5

Critical Contraindications

Absolute Contraindications:

• Pregnancy (causes fetal toxicity, oligohydramnios, fetal lung hypoplasia, skeletal deformations, and neonatal death in second and third trimesters) 1
• Symptomatic hypotension 1, 2
• Uncontrolled hyperkalemia 1, 2
• Bilateral renal artery stenosis 1, 2

Temporary Holds:

• Hold ARB during intercurrent illness, volume depletion, bowel preparation for colonoscopy, or prior to major surgery 5

Common Pitfalls to Avoid

• Do not use ARBs in normotensive diabetic patients without albuminuria - there is no evidence that ARBs prevent development of diabetic kidney disease in the absence of hypertension or albuminuria 5, 2
• Do not fail to titrate to maximum tolerated dose - the renoprotective effect is dose-dependent 1, 2
• Do not adjust diuretic dosages when initiating ARB without monitoring - this may lead to volume depletion 5
• Do not initiate ARB in patients with abrupt onset nephrotic syndrome - can cause acute kidney injury 5

Adjunctive Therapy

Restrict dietary sodium to <2.0 g/day (<90 mmol/day) as synergistic therapy with ARB treatment. 5