In a 68-year-old woman with chronic kidney disease, which antihypertensive agent should be initiated?

Antihypertensive Management in a 68-Year-Old Woman with CKD

Start an ACE inhibitor (such as lisinopril 10 mg daily) as the first-line antihypertensive agent, titrating to the maximum tolerated dose, and add a thiazide-like diuretic (chlorthalidone 12.5–25 mg daily) or a dihydropyridine calcium channel blocker (amlodipine 5–10 mg daily) if blood pressure remains above target. 1, 2

Blood Pressure Target

• Aim for a blood pressure < 130/80 mm Hg if this patient has albuminuria ≥ 30 mg/day (or albumin-to-creatinine ratio ≥ 30 mg/g), as this target provides optimal cardiovascular and renal protection. 1, 2
• If albuminuria is absent or < 30 mg/day, target < 140/90 mm Hg, because lower targets have not demonstrated additional kidney or cardiovascular benefit in non-albuminuric CKD. 2, 3
• The more aggressive systolic target < 120 mm Hg applies only when standardized automated office blood pressure measurement is used (5-minute rest, average of three readings); applying this target to routine office measurements leads to overtreatment. 1, 2

First-Line Pharmacologic Therapy

ACE Inhibitor as Initial Agent

• Initiate an ACE inhibitor (lisinopril 10 mg daily, ramipril 5 mg daily, or equivalent) immediately if albuminuria ≥ 300 mg/day is documented, as this is a strong (Class I, 1B) recommendation. 1, 2
• For moderately increased albuminuria (30–300 mg/day), either an ACE inhibitor or an ARB (losartan 50 mg daily) is appropriate as first-line therapy. 2
• If albuminuria is absent, an ACE inhibitor remains reasonable but is not mandatory; a dihydropyridine calcium channel blocker or thiazide diuretic may be used as initial therapy. 2, 3
• Titrate the ACE inhibitor to the maximum approved dose that the patient tolerates (e.g., lisinopril up to 40 mg daily, ramipril up to 10 mg daily), because trial benefits were achieved at these doses. 2, 4

If ACE Inhibitor Is Not Tolerated

• Substitute an ARB (losartan 50–100 mg daily, valsartan 80–160 mg daily) if the patient develops intolerable cough or angioedema on an ACE inhibitor; the renal and cardiovascular benefits are comparable. 1, 2

Monitoring After Initiating RAS Inhibition

• Check serum creatinine and potassium 2–4 weeks after starting or up-titrating an ACE inhibitor or ARB to screen for hyperkalemia and acute changes in kidney function. 2, 3
• Continue the ACE inhibitor or ARB unless serum creatinine rises > 30% within 4 weeks; a rise up to 30% is expected and reflects the intended hemodynamic effect of reducing intraglomerular pressure. 2, 5, 4
• Manage hyperkalemia with potassium-wasting diuretics (thiazide or loop diuretics), potassium binders (patiromer, sodium zirconium cyclosilicate), or dietary potassium restriction (< 2–3 g/day) rather than stopping the RAS inhibitor. 2
• Discontinue or reduce the ACE inhibitor/ARB only if hyperkalemia is uncontrolled despite these measures, the patient develops symptomatic hypotension, or the creatinine increase > 30% persists. 2, 5

Second-Line Antihypertensive Therapy

• Add a thiazide-like diuretic (chlorthalidone 12.5–25 mg daily or indapamide 1.25–2.5 mg daily) as the second agent when blood pressure remains uncontrolled on ACE inhibitor monotherapy; thiazide-like agents provide superior cardiovascular event reduction compared with hydrochlorothiazide. 2
• Alternatively, add a dihydropyridine calcium channel blocker (amlodipine 5–10 mg daily, nifedipine extended-release 30–60 mg daily) as the second agent. 1, 2
• Do not use a non-dihydropyridine calcium channel blocker (diltiazem, verapamil) in combination with an ACE inhibitor or ARB, as dihydropyridine agents are preferred for additive blood pressure lowering without negative inotropic effects. 1
• A single-pill fixed-dose combination of an ACE inhibitor plus the chosen second agent (e.g., lisinopril/amlodipine, lisinopril/hydrochlorothiazide) is strongly recommended to improve adherence. 2

Third-Line and Resistant Hypertension

• If blood pressure remains uncontrolled on dual therapy, add the third class not yet used (the remaining thiazide-like diuretic or calcium channel blocker), creating an ACE inhibitor + calcium channel blocker + thiazide regimen; a single-pill triple combination is preferred. 2
• For resistant hypertension (uncontrolled on three agents including a diuretic), add a mineralocorticoid receptor antagonist (spironolactone 25–50 mg daily or eplerenone 50–100 mg daily) with close monitoring for hyperkalemia. 2
• Beta-blockers may be added when there are compelling indications such as coronary artery disease, heart failure with reduced ejection fraction, or atrial fibrillation. 2

Critical Contraindications

• Never combine an ACE inhibitor with an ARB (dual RAS blockade), as this increases the risk of hyperkalemia, hypotension, and acute kidney injury without added benefit; this is a strong (Class III) contraindication. 1, 2
• Avoid triple therapy that adds a direct renin inhibitor (aliskiren) to an ACE inhibitor or ARB. 1

Lifestyle Modifications

• Limit dietary sodium to < 2 g/day (≈ 5 g salt), as sodium restriction enhances the antiproteinuric effect of ACE inhibitors and improves blood pressure control. 2, 3
• Restrict protein intake to ≈ 0.8 g/kg/day for CKD stage 3 or higher and avoid high-protein diets > 1.3 g/kg/day, which may accelerate kidney function decline. 2
• Encourage tobacco cessation. 2
• Promote at least 150 minutes per week of moderate-intensity physical activity. 2
• Maintain a healthy body weight appropriate for age and comorbidities. 2

Follow-Up and Monitoring Schedule

• Schedule clinic visits every 6–8 weeks until the blood pressure target is safely achieved; thereafter, follow up every 3–6 months based on medication regimen and patient stability. 2
• Implement home blood pressure monitoring during medication titration to prevent hypotension (systolic < 110 mm Hg). 2
• Repeat a basic metabolic panel 2–4 weeks after adding or adjusting any agent that affects electrolytes or renal function; monitor for hyperkalemia, acute kidney injury, and changes in eGFR. 2, 3
• Assess patients for symptoms of hypotension such as fatigue, light-headedness, or dizziness at each visit. 2, 6
• Measure urine albumin-to-creatinine ratio annually to detect new-onset albuminuria, which would prompt intensification of RAS inhibition and lower blood pressure targets. 2

Patient Education: Sick-Day Management

• Instruct the patient to hold or reduce antihypertensive doses during acute illnesses with vomiting, diarrhea, or reduced oral intake to prevent volume depletion and acute kidney injury. 2, 6
• Teach the patient to watch for symptoms of hypotension such as fatigue, light-headedness, or dizziness. 2

Common Pitfalls to Avoid

• Do not apply the < 120 mm Hg systolic target to routine office blood pressure measurements; it requires standardized automated measurement (5-minute rest, average of three readings). 1, 2
• Do not discontinue an ACE inhibitor or ARB for a creatinine rise < 30%; this reflects the intended hemodynamic effect of reducing intraglomerular pressure and is associated with long-term renoprotection. 2, 5, 4
• Never combine an ACE inhibitor with an ARB, as this increases harm without benefit. 1, 2
• Do not use dihydropyridine calcium channel blockers as monotherapy in patients with albuminuria; they should be combined with an ACE inhibitor or ARB. 1

Special Considerations for Elderly Patients

• Age alone should not preclude appropriate blood pressure control; frail elderly patients in SPRINT derived the same cardiovascular and mortality benefit from intensive blood pressure lowering as younger patients. 1
• However, patients with symptomatic postural hypotension or limited life expectancy may warrant less intensive blood pressure targets; check orthostatic vital signs at every visit. 1, 6