Should lisinopril be increased or hydralazine added for uncontrolled hypertension in a patient with CKD stage 3B?

Uncontrolled Hypertension Management in CKD Stage 3B

Direct Recommendation

Optimize the current regimen first by increasing lisinopril to 20-40 mg daily and maximizing furosemide to 40-80 mg twice daily before adding hydralazine, given this patient's CKD stage 3B, African American ethnicity, and suboptimal dosing of existing medications. 1, 2

Rationale for Dose Optimization Over Adding Hydralazine

Current Regimen Assessment

• The patient is on suboptimal doses of all current medications: lisinopril 10 mg (usual range 10-40 mg), amlodipine 10 mg (at maximum), carvedilol 12.5 mg twice daily (moderate dose), and furosemide 20 mg daily (low dose for CKD 3B) 1, 2
• Suboptimal therapy is the most common reason for failure to reach blood pressure goals in resistant hypertension 3
• The BP of 190/100 mmHg represents stage 2 hypertension requiring immediate intensification 1

Specific Medication Adjustments

ACE Inhibitor Optimization:

• Increase lisinopril from 10 mg to 20 mg initially, with potential titration to 40 mg daily 1, 2
• The FDA label specifically states lisinopril can be dosed up to 40 mg daily for hypertension 2
• In CKD stage 3B (eGFR 30-44 mL/min), no dose adjustment is required as creatinine clearance is >30 mL/min 2
• ACE inhibitors are first-line therapy in CKD patients and provide renoprotection 4, 5

Diuretic Optimization:

• Increase furosemide from 20 mg daily to 40-80 mg twice daily 1
• Loop diuretics are preferred over thiazides in moderate-to-severe CKD (GFR <30 mL/min), and this patient with CKD 3B is approaching this threshold 1
• In African American patients with CKD, adequate diuretic therapy is critical for BP control 5
• Higher doses of diuretics are usually needed in truly drug-resistant hypertension, especially with CKD 3

Why Not Hydralazine Initially

Hydralazine should be reserved as a later-line agent due to significant safety concerns:

• Hydralazine can cause severe acute kidney injury resulting in CKD progression or death, with documented cases of ANCA-associated vasculitis 6
• The drug has an "extremely unfavorable adverse-event profile" and should be used cautiously given widespread availability of alternative agents 6
• When hydralazine is used, it requires addition of a beta-blocker (which this patient already has with carvedilol) to control reflex tachycardia 7
• Hydralazine is recommended primarily for resistant hypertension after optimizing three-drug regimens 1, 7

Stepwise Approach for This Patient

Step 1 (Immediate):

• Increase lisinopril to 20 mg daily 1, 2
• Increase furosemide to 40 mg twice daily 1
• Continue amlodipine 10 mg and carvedilol 12.5 mg twice daily 1

Step 2 (If BP remains >140/90 after 2-4 weeks):

• Increase lisinopril to 40 mg daily 2
• Consider increasing furosemide to 80 mg twice daily 1

Step 3 (If still uncontrolled):

• Add spironolactone 25-50 mg daily (preferred fourth agent in resistant hypertension) 1, 7
• Monitor potassium closely given ACE inhibitor use and CKD 1, 4

Step 4 (Only if above fails):

• Consider hydralazine 25-50 mg twice daily with close monitoring for adverse effects 7, 6

Critical Monitoring Parameters

With ACE inhibitor dose increase:

• Monitor serum creatinine and potassium within 1-2 weeks 4
• A creatinine increase up to 30% is acceptable and indicates hemodynamic effect 4
• Watch for hyperkalemia, especially with concurrent diuretic adjustment 1, 4

With loop diuretic increase:

• Monitor for volume depletion and hypotension 2
• Assess electrolytes (potassium, sodium, magnesium) 1
• Monitor renal function 2

Special Considerations for African American Patients with CKD

• Calcium channel blockers and thiazide-type diuretics are recommended as initial therapy in black hypertensive populations 5
• This patient appropriately has amlodipine (CCB) as part of the regimen 5
• ACE inhibitors or ARBs are specifically recommended in CKD to improve kidney outcomes regardless of race 5
• The combination of ACE inhibitor + CCB + loop diuretic is appropriate for this population 1, 5