Is lisinopril (Angiotensin-Converting Enzyme inhibitor) with Hydrochlorothiazide (HCTZ) (Thiazide Diuretic) suitable for patients with Chronic Kidney Disease (CKD) stage 3?

Lisinopril-HCTZ in CKD Stage 3: Recommendations

Lisinopril-HCTZ combination therapy is not recommended as first-line treatment for patients with CKD stage 3, but ACE inhibitors alone (like lisinopril) are reasonable to slow kidney disease progression. 1

ACE Inhibitors in CKD Stage 3

Benefits

• ACE inhibitors are recommended for CKD stage 3 patients with hypertension to slow kidney disease progression (Class IIa recommendation) 1
• Target blood pressure goal should be <130/80 mmHg in CKD patients 1
• ACE inhibitors provide renoprotective effects beyond blood pressure lowering, particularly in patients with albuminuria (≥300 mg/day) 1

Dosing Considerations

• Start with low-dose lisinopril (≤10 mg/day) in CKD stage 3 patients 1
• Gradually titrate dose while monitoring renal function and potassium levels
• Even patients with CKD may require dose titration above standard doses to achieve target blood pressure 1

Concerns with HCTZ Addition in CKD Stage 3

Potential Issues

• Thiazide diuretics like HCTZ have reduced efficacy when eGFR falls below 30 mL/min/1.73m² (late stage 3 CKD)
• Risk of electrolyte abnormalities is higher in CKD patients, particularly:
  • Hyponatremia
  • Hypokalemia (which can worsen with ACE inhibitor-induced hyperkalemia)
  • Metabolic alkalosis
• Increased risk of acute kidney injury, particularly in volume-depleted patients

Alternative Approach

Stepped Therapy Algorithm

1. First step: Start with ACE inhibitor alone (lisinopril) at low dose (5-10 mg) 1
2. Monitor: Check renal function and electrolytes 1-2 weeks after initiation
3. Titration: If BP remains above target and no adverse effects:
   • Increase lisinopril dose gradually (up to 40 mg daily if tolerated) 1
4. If additional therapy needed:
   • For eGFR >30 mL/min: Consider adding low-dose HCTZ (12.5 mg) with careful monitoring 2, 3
   • For eGFR <30 mL/min: Consider loop diuretic instead of thiazide 1
   • Alternative: Add calcium channel blocker (especially in transplant patients) 1

Evidence for Combination Therapy

Some research suggests that carefully monitored combination therapy may provide benefits:

• A study showed that losartan-HCTZ combination provided better blood pressure control and reduced proteinuria compared to losartan alone in stage 3 CKD patients 2
• Low-dose HCTZ (12.5 mg) added to RAS blockade improved blood pressure control without significant adverse effects in selected patients 3

Monitoring Requirements

If using lisinopril (with or without HCTZ) in CKD stage 3:

• Check serum creatinine and potassium within 1-2 weeks of initiation or dose change
• Monitor for hypotension, especially in volume-depleted patients
• For stage 3 CKD, laboratory evaluations generally indicated every 6-12 months 1
• More frequent monitoring (every 3-4 months) if using combination therapy

Cautions and Contraindications

• Avoid in patients with history of angioedema with ACE inhibitors
• Use caution in patients with bilateral renal artery stenosis
• Monitor for hyperkalemia, especially if patient is on other potassium-sparing medications
• Avoid in pregnancy (FDA Category D)

In summary, while ACE inhibitors like lisinopril are beneficial in CKD stage 3, adding HCTZ requires careful consideration of risks versus benefits. Start with lisinopril alone and add HCTZ only if necessary for blood pressure control, with appropriate monitoring of renal function and electrolytes.