What antihypertensive medication should I start in a patient with uncontrolled hypertension (blood pressure 150/90 mmHg) and impaired renal function (GFR 27), currently on Hydrochlorothiazide (HCTZ)?

Antihypertensive Management for Patient with CKD and Uncontrolled Hypertension

An ACE inhibitor or ARB should be the first-line antihypertensive medication for this patient with uncontrolled hypertension (BP 150/90 mmHg) and impaired renal function (GFR 27), replacing HCTZ which is less effective in advanced CKD. 1, 2

Medication Selection Algorithm

First-Line Agent

• ACE inhibitor (e.g., lisinopril) or ARB (e.g., losartan)
  • These are specifically recommended for patients with CKD and albuminuria 1
  • Maximum tolerated dose should be used for optimal blood pressure and renoprotective effects
  • Patient's GFR of 27 places her in advanced CKD, where ACEi/ARBs still provide cardiovascular benefit without significantly increasing risk of end-stage kidney disease 1

Considerations for HCTZ Replacement

1. Efficacy issue: HCTZ loses effectiveness at lower GFR levels
2. Better alternative: Replace with a long-acting thiazide-like diuretic (chlorthalidone or indapamide) if diuretic therapy is needed 1, 3
   • Chlorthalidone has been shown to reduce BP by approximately 10.5/3.1 mmHg in patients with advanced CKD 3

Medication Regimen Building

1. Start with ACEi/ARB at low dose and titrate upward
2. Add calcium channel blocker (preferably dihydropyridine) if BP remains uncontrolled
3. Consider thiazide-like diuretic (chlorthalidone) as third agent if needed
4. Add mineralocorticoid receptor antagonist (spironolactone) as fourth agent if BP remains uncontrolled 1, 2

Monitoring Recommendations

Short-term Monitoring

• Check renal function and electrolytes within 1-2 weeks after starting ACEi/ARB 2, 4
• Monitor for hyperkalemia, especially important in CKD 4, 5
• Watch for acute changes in renal function (up to 30% increase in creatinine may be acceptable) 4

Long-term Monitoring

• BP target should be <130/80 mmHg 1, 2
• Regular monitoring of renal function every 1-3 months once stable 2
• Monitor for adverse effects of medications:
  • ACEi: cough, angioedema 4
  • ARB: less cough but still risk of hyperkalemia 5
  • Thiazide-like diuretics: electrolyte abnormalities, hyperuricemia 3

Important Considerations

Medication-Specific Cautions

• ACEi (lisinopril): Risk of hyperkalemia, acute kidney injury, and angioedema; monitor closely 4
• ARB (losartan): Better tolerated than ACEi with lower incidence of cough, but still requires monitoring for hyperkalemia 5, 6
• Thiazide-like diuretics: Can be effective even in advanced CKD but require close monitoring for electrolyte abnormalities 3, 7, 8

Common Pitfalls to Avoid

• Don't use combination of ACEi and ARB - increases adverse effects without additional benefit 1
• Don't discontinue ACEi/ARB just because of small increases in creatinine (up to 30% increase may be acceptable) 2
• Don't assume thiazides won't work in advanced CKD - evidence shows they can still be effective 3, 8
• Don't forget to check for orthostatic hypotension, especially when adding multiple agents 2

By following this evidence-based approach, you can effectively manage this patient's hypertension while protecting renal function and minimizing adverse effects.