In a Black adult with stage G3a chronic kidney disease (eGFR ≈ 52 mL/min/1.73 m²) and normal albuminuria, how should hypertension and renal protection be managed when ACE inhibitors and angiotensin receptor blockers are avoided due to risk of angioedema?

Management of Hypertension and Renal Protection in Black Adults with Stage G3a CKD When ACE Inhibitors and ARBs Are Contraindicated

When ACE inhibitors and ARBs cannot be used due to angioedema risk in a Black patient with stage G3a CKD and normal albuminuria, initiate a calcium channel blocker (preferably amlodipine) as first-line therapy, either alone or combined with a thiazide-type diuretic, targeting blood pressure <140/90 mmHg. 1, 2

Blood Pressure Target for This Clinical Scenario

• Target <140/90 mmHg for CKD patients without significant albuminuria (normal albuminuria), as lower targets have not demonstrated additional kidney or cardiovascular benefit in this population. 2
• The more aggressive <130/80 mmHg or <120 mmHg targets apply specifically to patients with albuminuria ≥30 mg/day, which does not apply to this patient. 2

First-Line Antihypertensive Selection

Calcium Channel Blockers as Primary Therapy

• Calcium channel blockers (particularly dihydropyridines like amlodipine or nifedipine) are recommended as first-line therapy for hypertension in Black patients, demonstrating superior blood pressure lowering and cardiovascular event reduction compared to RAS inhibitors in this population. 1
• CCBs are equally effective as thiazide diuretics in reducing blood pressure, cardiovascular disease, and stroke events in Black adults. 1
• For CKD without albuminuria, initial therapy with a dihydropyridine calcium channel blocker is appropriate and does not require RAS inhibition. 2

Thiazide-Type Diuretics as Alternative or Combination

• Thiazide-type diuretics (chlorthalidone or indapamide preferred over hydrochlorothiazide) are equally effective first-line options for Black patients with hypertension. 1
• The most effective combination for Black patients is CCB + thiazide diuretic, which should be considered if monotherapy is insufficient. 1

Rationale for Avoiding RAS Inhibitors in This Case

• In CKD patients without significant albuminuria, RAS inhibitors (ACE inhibitors or ARBs) are not mandatory and offer no advantage over calcium channel blockers or thiazide diuretics. 2
• The renoprotective benefits of ACE inhibitors and ARBs are primarily demonstrated in patients with albuminuria ≥30 mg/day; this patient has normal albuminuria. 2, 3
• Given the history of angioedema concern and absence of albuminuria, there is no compelling indication to use RAS inhibitors in this patient. 1

Treatment Algorithm

Step 1: Initiate Monotherapy

• Start amlodipine 5 mg daily or chlorthalidone 12.5-25 mg daily. 1
• Monitor blood pressure response over 3 months. 1

Step 2: Combination Therapy if Target Not Achieved

• Add the second agent (CCB + thiazide diuretic combination) if blood pressure remains ≥140/90 mmHg on monotherapy. 1, 2
• Consider single-pill fixed-dose combination to improve adherence. 2
• Most Black patients require ≥2 medications to achieve blood pressure control. 1

Step 3: Additional Agents for Resistant Hypertension

• If blood pressure remains uncontrolled on CCB + thiazide diuretic, add a beta-blocker (especially if coronary artery disease or heart failure is present). 2, 4
• For resistant hypertension (uncontrolled on three agents including a diuretic), add a mineralocorticoid receptor antagonist with close monitoring for hyperkalemia. 2

Monitoring Strategy

Initial Monitoring

• Check basic metabolic panel (serum creatinine, eGFR, potassium) 2-4 weeks after initiating or adjusting diuretic therapy. 2
• Schedule clinic visits every 6-8 weeks until blood pressure target <140/90 mmHg is achieved. 2
• Implement home blood pressure monitoring to prevent hypotension (systolic <110 mmHg). 2

Long-Term Monitoring

• Monitor eGFR and serum creatinine at least annually (2-4 times per year for stage G3a CKD). 3
• Continue monitoring urine albumin-to-creatinine ratio annually, as development of albuminuria would change the treatment approach. 3, 2
• Follow up every 3-6 months once blood pressure is controlled. 2

Lifestyle Modifications

• Restrict dietary sodium to <2 g/day (approximately 5 g salt), as this is particularly important for blood pressure control in Black patients who tend to be salt-sensitive. 2
• Encourage at least 150 minutes per week of moderate-intensity physical activity. 2
• Maintain protein intake at approximately 0.8 g/kg/day for stage G3a CKD. 2
• Promote tobacco cessation if applicable. 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
• Educate about symptoms of hypotension (fatigue, light-headedness, dizziness) and when to seek medical attention. 2

Critical Considerations Specific to Black Patients

eGFR Calculation

• Use the race-free CKD-EPI equation (2021) for eGFR calculation, as recommended by the NKF-ASN Task Force, which removes the race multiplier that previously assigned higher eGFR values to Black patients. 3
• The removal of the race multiplier may reclassify some Black patients to more severe CKD stages, potentially making them eligible for earlier interventions. 3, 5

Angioedema Risk Context

• While ACE inhibitors carry a higher risk of angioedema in Black patients compared to other racial groups, this patient's specific contraindication makes the point moot—CCBs and thiazides are excellent alternatives without this risk. 1
• Never attempt dual RAS blockade (ACE inhibitor + ARB) even if angioedema risk were not a concern, as this increases harm without benefit. 2, 4

Common Pitfalls to Avoid

• Do not apply the <130/80 mmHg or <120 mmHg blood pressure targets to patients without albuminuria, as these intensive targets have not shown benefit in this population and may cause harm. 2
• Do not assume that all CKD patients require RAS inhibition; the absence of albuminuria makes CCBs and thiazides equally appropriate first-line choices. 2
• Do not withhold effective antihypertensive therapy due to concerns about modest eGFR decline; stable kidney function is expected with appropriate blood pressure control. 3
• Avoid using loop diuretics instead of thiazide-type diuretics at this stage of CKD (eGFR ≈52 mL/min/1.73 m²); thiazides remain effective until eGFR falls below 30 mL/min/1.73 m². 2

When to Reassess the Treatment Strategy

• If the patient develops albuminuria ≥30 mg/g on follow-up testing, the treatment approach must be reconsidered. At that point, the benefits of RAS inhibition would need to be weighed against the angioedema risk, potentially requiring specialist consultation. 2
• If eGFR declines to stage G3b or worse (eGFR <45 mL/min/1.73 m²), consider nephrology referral for comprehensive CKD management. 3
• If blood pressure remains uncontrolled despite triple therapy (CCB + thiazide + third agent), refer to nephrology or hypertension specialist. 2