What antihypertensive should be added for a 44‑year‑old with chronic kidney disease stage 3 (eGFR ≈ 32 mL/min/1.73 m²) already on lisinopril 20 mg twice daily?

Blood Pressure Medication to Add for Stage 3 CKD on Lisinopril

Add a dihydropyridine calcium channel blocker (such as amlodipine 5 mg daily) as the second-line agent, as this combination provides superior blood pressure control and renal protection compared to adding a diuretic in patients with CKD stage 3. 1

Rationale for Calcium Channel Blocker as Second-Line Agent

The KDIGO guideline explicitly addresses this clinical scenario and identifies that when a patient with CKD is already receiving an ACE inhibitor (lisinopril in this case), the choice of second-line therapy should prioritize either a calcium channel blocker or a diuretic 1. However, post hoc analysis of large trials demonstrates that combining an ACE inhibitor with a calcium channel blocker is more likely to slow CKD progression than combining an ACE inhibitor with a diuretic 1.

Why Not Add an ARB

• Dual RAAS blockade (ACE inhibitor + ARB) should be avoided because multiple large cardiology trials and the HALT-PKD trial have demonstrated harms without additional benefit 1, 2
• The HALT-PKD trial specifically studied patients with stage 3 CKD (eGFR 25-60 mL/min/1.73 m²) and found that adding telmisartan to lisinopril did not alter the decline in eGFR and increased risks of hyperkalemia and acute kidney injury 2
• The 2017 ACC/AHA guideline explicitly states that the combination of an ACE inhibitor and ARB should be avoided due to reported harms 1

Why Not Add a Diuretic First

While diuretics are a reasonable second-line option and augment the antihypertensive and antialbuminuric effects of ACE inhibitors 1, they have important limitations:

• Thiazide diuretics have minimal efficacy when eGFR <30 mL/min/1.73 m² 3
• At eGFR 32 mL/min/1.73 m², this patient is approaching the threshold where thiazides become ineffective
• Loop diuretics would be required if eGFR declines further, but calcium channel blockers remain effective at all levels of renal function
• Diuretics tend to cause hyperglycemia, which may be problematic if the patient has diabetes 1

Specific Medication Recommendations

First Choice: Dihydropyridine Calcium Channel Blocker

• Start amlodipine 5 mg once daily, which can be titrated to 10 mg daily if needed for blood pressure control 1
• Amlodipine requires no dose adjustment in renal impairment 3
• Alternative dihydropyridine options include nifedipine extended-release or felodipine

Blood Pressure Target

• Target blood pressure is <130/80 mm Hg for patients with CKD, based on the SPRINT trial which included 28% of patients with stage 3-4 CKD and demonstrated cardiovascular and mortality benefits with intensive blood pressure management 1
• The 2017 ACC/AHA guideline provides strong evidence (Class I) for this lower target in all patients with CKD 1

Monitoring Requirements After Adding Calcium Channel Blocker

• Check serum creatinine and eGFR within 4 weeks of adding the new medication 1
• Monitor blood pressure at 2-4 week intervals until target is achieved 1
• Check serum potassium within 4 weeks if potassium is >4.5 mEq/L at baseline, as the patient is already on an ACE inhibitor 1
• Once blood pressure is at goal and doses are stable, monitor eGFR every 3-6 months given the stage 3 CKD 1, 3

Additional Considerations for This Patient

Assess for Albuminuria

• Measure urine albumin-to-creatinine ratio (UACR) if not already done, as this guides additional therapy 1
• If UACR ≥200 mg/g, consider adding an SGLT2 inhibitor (dapagliflozin 10 mg daily) for renal and cardiovascular protection, as this can be initiated at eGFR ≥20 mL/min/1.73 m² 1, 4
• SGLT2 inhibitors reduce CKD progression by 39-44% and cardiovascular events by 29% in patients with CKD and albuminuria 1, 4

Optimize Current ACE Inhibitor Dose

• The current dose of lisinopril 20 mg BID (40 mg total daily) is appropriate and should be continued 1
• ACE inhibitors should be titrated to moderate-to-maximal doses approved for hypertension treatment 1
• Continue lisinopril even if eGFR declines below 30 mL/min/1.73 m², as the renoprotective benefits persist at lower eGFR levels 1

Dietary Sodium Restriction

• Recommend dietary sodium restriction to <2.3 g/day (100 mmol/day), as this is critical to optimize the effectiveness of both the ACE inhibitor and any additional antihypertensive medication 1
• Sodium restriction augments the antihypertensive and antialbuminuric effects of ACE inhibitors 1

Common Pitfalls to Avoid

• Do not add an ARB to the existing ACE inhibitor, as this increases harm without benefit 1, 2
• Do not discontinue or reduce the ACE inhibitor dose if serum creatinine rises up to 30% within 4 weeks of adding the calcium channel blocker, as this is an expected hemodynamic effect that correlates with long-term renoprotection 1, 5
• Do not use chlorthalidone or hydrochlorothiazide as the second agent at this eGFR level, as efficacy is limited when eGFR <30-40 mL/min/1.73 m² 3
• Monitor for peripheral edema with calcium channel blockers, which occurs in approximately 10-15% of patients but is not dangerous and can be managed by adding a low-dose diuretic if needed 1

If Blood Pressure Remains Uncontrolled on Three Agents

If blood pressure remains above target on lisinopril + calcium channel blocker + diuretic:

• Add a mineralocorticoid receptor antagonist (spironolactone 25 mg daily or eplerenone 50 mg daily) for resistant hypertension 1
• Monitor serum potassium closely (within 1 week, then monthly for 3 months) when adding an MRA to an ACE inhibitor 1
• Consider referral to nephrology for further evaluation of secondary causes of hypertension 6