How to manage uncontrolled hypertension with worsening microalbuminuria in a patient on Perindopril (Angiotensin-Converting Enzyme inhibitor) and Amlodipine (Calcium Channel Blocker)?

Management of Uncontrolled Hypertension with Worsening Microalbuminuria

For a patient with uncontrolled hypertension and worsening microalbuminuria, the optimal approach is to intensify RAS blockade by increasing perindopril dosage to the maximum recommended dose and adding a thiazide-like diuretic while targeting a blood pressure of <130/80 mmHg.

Current Clinical Situation Assessment

The patient presents with:

• Uncontrolled hypertension (BP 140/95) despite being on:
  • Perindopril 8mg daily (2 tablets of 4mg)
  • Amlodipine 10mg daily
• Worsening microalbuminuria:
  • Urine albumin/creatinine ratio increased from 2.6 to 6.2
  • Urine microalbumin increased from 83 to 89
• Normal eGFR >90
• Normal HbA1c (39 mmol/mol)

Treatment Approach

Step 1: Optimize RAS Blockade

• Increase perindopril to maximum dose
  • Current guidelines recommend maximizing ACE inhibitor dosage in patients with albuminuria 1
  • Perindopril can be increased to 16mg daily (4 tablets of 4mg) 1
  • ACE inhibitors have superior antiproteinuric effects compared to other antihypertensive classes 1

Step 2: Add a Diuretic

• Add a thiazide-like diuretic (e.g., indapamide 1.5mg SR daily)
  • Most patients with hypertension and CKD require combination therapy 1
  • Diuretics work synergistically with ACE inhibitors to reduce BP and preserve renal function 2
  • Indapamide/amlodipine combination has shown superior SBP reduction in diabetic patients with microalbuminuria 3

Step 3: Adjust Medication Timing

• Recommend taking all medications in the morning
  • Patient currently takes medications in afternoon/evening due to work schedule
  • This may contribute to elevated morning BP readings
  • If morning dosing is not possible due to work schedule, consider splitting the dose

Step 4: Set Target Blood Pressure

• Target BP <130/80 mmHg
  • KDIGO guidelines recommend BP <130/80 mmHg for patients with albuminuria 1
  • More aggressive BP target (<130/80 mmHg) is recommended for patients with microalbuminuria to slow progression of kidney disease 1

Monitoring Plan

1. Short-term monitoring (7-14 days after medication changes):

   • Check serum creatinine, potassium, and eGFR 4
   • Monitor for symptoms of hypotension, especially with increased ACE inhibitor dose

2. Regular follow-up (every 3 months):

   • BP measurements
   • Urine albumin/creatinine ratio
   • Renal function (eGFR, creatinine)
   • Electrolytes, particularly potassium

Lifestyle Modifications

• Sodium restriction: Target <2g sodium per day 1
• Protein intake: Recommend 0.8 g/kg/day 1, 4
• Adequate hydration: Explain that while hydration is important, poor water intake is not the primary cause of microalbuminuria
• Avoid nephrotoxic agents: Recommend avoiding NSAIDs and caution with radiocontrast procedures 1, 4

Potential Pitfalls and Considerations

1. Risk of hyperkalemia:

   • Monitor potassium levels closely when increasing ACE inhibitor dose
   • Consider dietary potassium restriction if levels begin to rise

2. Acute kidney injury risk:

   • A temporary rise in creatinine (up to 30%) may occur with increased ACE inhibitor dose
   • This is generally acceptable if it stabilizes within 4 weeks

3. Avoid dual RAS blockade:

   • Do not add an ARB to the current ACE inhibitor regimen
   • Combination of ACE inhibitor and ARB increases adverse effects without additional benefit 1, 4

4. Alternative approach if unsuccessful:

   • If BP remains uncontrolled despite maximum ACE inhibitor dose and addition of diuretic, consider adding a non-dihydropyridine calcium channel blocker (e.g., diltiazem) 1
   • These have better antiproteinuric effects than dihydropyridine CCBs like amlodipine 1

By following this approach, you should be able to achieve better blood pressure control and reduce microalbuminuria, thereby protecting kidney function and reducing cardiovascular risk in this patient.