In a 56-year-old man with type 2 diabetes, hypertension, and chronic kidney disease already taking losartan 100 mg daily, pregabalin, and insulin lispro (Humalog), what additional antihypertensive medication(s) can be added?

Additional Antihypertensive Therapy for Diabetic Kidney Disease

Add a thiazide-like diuretic (chlorthalidone 12.5-25 mg daily) or loop diuretic (furosemide 20-40 mg daily) to the existing losartan regimen, as this patient requires combination therapy to achieve blood pressure control below 130/80 mmHg. 1

Optimizing Current RAS Blockade

Before adding additional agents, ensure the losartan dose is maximized:

• Uptitrate losartan to 100 mg daily if not already at this dose, as the target dose for diabetic nephropathy is 100 mg once daily to provide optimal renal and cardiovascular protection. 1, 2
• The patient is currently on 100 mg, which is appropriate, but confirm this is being taken consistently. 1, 3
• Monitor serum creatinine and potassium 2-4 weeks after any dose adjustment; continue therapy unless creatinine rises >30% within 4 weeks. 1, 4

First-Line Add-On Therapy: Diuretics

Diuretics are the preferred second agent after RAS blockade in patients with diabetes, hypertension, and CKD:

• Chlorthalidone 12.5-25 mg once daily is the preferred thiazide-like diuretic for this population, offering superior cardiovascular outcomes compared to hydrochlorothiazide. 4
• Loop diuretics (furosemide 20-40 mg daily) may be more appropriate if the patient has significant volume overload or if eGFR is substantially reduced (typically <30 mL/min/1.73 m²), as thiazides lose efficacy at lower GFR levels. 1, 5
• The combination of an ARB plus diuretic is guideline-endorsed first-line therapy and has demonstrated efficacy in reducing cardiovascular events. 4

Alternative Second-Line Agent: Calcium Channel Blockers

If diuretics are contraindicated or not tolerated:

• Add a dihydropyridine calcium channel blocker such as amlodipine 5-10 mg daily, which provides additive blood pressure lowering without interfering with RAS blockade. 1, 4
• Amlodipine can be used safely with losartan and does not increase hyperkalemia risk. 6

Blood Pressure Targets

• Target blood pressure <130/80 mmHg for patients with diabetes and CKD to reduce cardiovascular risk and slow kidney disease progression. 1, 4
• The 2020 KDIGO guideline recommends systolic blood pressure <120 mmHg when tolerated, though this more aggressive target should be individualized based on tolerability. 1
• Reassess blood pressure every 2-4 weeks during medication titration, aiming to reach target within 3 months. 4

Triple Therapy if Needed

If blood pressure remains uncontrolled on losartan plus one additional agent:

• Add a third agent from a different class (ARB + diuretic + calcium channel blocker), creating guideline-recommended triple therapy. 4
• This combination (losartan + chlorthalidone + amlodipine) addresses three complementary mechanisms and is highly effective. 4

Critical Safety Considerations

Avoid these dangerous combinations:

• Never combine losartan with an ACE inhibitor or direct renin inhibitor (aliskiren), as dual RAS blockade increases hyperkalemia, syncope, and acute kidney injury by 2-3 fold without cardiovascular benefit. 1, 4, 7
• Do not add spironolactone or other potassium-sparing diuretics unless hyperkalemia can be carefully managed, as the patient already has CKD and is on an ARB. 1

Monitoring Protocol

After adding any antihypertensive agent:

• Check serum creatinine, eGFR, and potassium within 2-4 weeks of medication initiation or dose change. 1, 4
• Manage hyperkalemia medically first (dietary potassium restriction, increase diuretic dose, add sodium bicarbonate if acidotic, or use GI potassium binders) before reducing or stopping losartan. 1, 4
• Only discontinue losartan if potassium remains >5.5 mmol/L despite these measures or if symptomatic hypotension develops. 1, 4

Common Pitfalls to Avoid

• Do not rely on losartan monotherapy for blood pressure control in diabetic CKD; combination therapy is almost always required. 1, 4
• Do not underdose the ARB; less than 25% of patients are titrated to target doses in clinical practice, yet higher doses provide superior renoprotection. 3, 2
• Do not stop losartan for mild creatinine elevations (up to 30% increase); this reflects beneficial hemodynamic changes, not kidney injury. 1
• Do not add beta-blockers as second- or third-line agents unless there are compelling indications (heart failure, post-MI, angina), as they are less effective than diuretics or calcium channel blockers for stroke prevention. 4