What are the drugs and doses for managing hypertension in patients undergoing hemodialysis?

Hypertension Management in Hemodialysis: Drugs and Doses

First-Line Pharmacological Approach

Start with ACE inhibitors or ARBs as first-line antihypertensive therapy in hemodialysis patients, with beta-blockers preferred if the patient has prior myocardial infarction or established coronary artery disease. 1, 2, 3

ACE Inhibitors (Preferred First-Line)

• Non-dialyzable ACE inhibitors (benazepril, fosinopril) are preferred over dialyzable ones to maintain consistent drug levels 2
• Lisinopril: For hemodialysis patients (creatinine clearance <10 mL/min), start at 2.5 mg once daily, titrate up to maximum 40 mg daily as tolerated 4
• Trandolapril: Can be dosed 2 mg three times weekly after each hemodialysis session for directly observed therapy 5
• ACE inhibitors reduce left ventricular hypertrophy and are associated with decreased mortality in dialysis cohorts 1, 6

Angiotensin Receptor Blockers (Alternative First-Line)

• ARBs may be more potent than ACE inhibitors at reducing left ventricular hypertrophy 1
• ARBs reduce left ventricular mass index and may preserve residual kidney function, particularly in peritoneal dialysis patients 3

Beta-Blockers (First-Line for CAD/Post-MI)

• Atenolol: Dosed three times weekly after hemodialysis due to prolonged half-life in ESRD; this enhances BP control through directly observed therapy 7, 5, 8
• Carvedilol or labetalol: Alternative beta-blockers 2
• Beta-blockers decrease mortality, blood pressure, ventricular arrhythmias, and improve left ventricular function in ESRD patients 1, 7
• Caution: Non-selective beta-blockers can increase serum potassium, particularly during fasting or exercise 7

Second-Line Agents

Calcium Channel Blockers

• Amlodipine: Long-acting dihydropyridine, associated with decreased total and cardiovascular mortality in observational studies 1, 3
• Amlodipine reduced cardiovascular events compared with placebo in randomized controlled trials of hemodialysis patients 3
• Can be dosed three times weekly after hemodialysis as part of directly observed therapy regimen 5

Anti-Adrenergic Agents

• Transdermal clonidine: Applied once weekly for noncompliant patients who cannot adhere to oral medications 7

Third-Line and Resistant Hypertension

Direct Vasodilators

• Minoxidil: Reserved for severe, resistant hypertension when three-drug regimen fails 1, 7
• Hydralazine: Alternative direct vasodilator 1

Mineralocorticoid Receptor Antagonists

• Spironolactone: Has shown cardiovascular benefits in some trials but carries significant risk of hyperkalemia 3, 8
• Use with extreme caution and close potassium monitoring 8

Treatment Algorithm

Step 1: Non-Pharmacological Management (Always First)

• Achieve dry weight through gradual ultrafiltration intensification 2
• Strict sodium restriction: <1500 mg/day 2
• Use low-sodium dialysate 2

Step 2: Initial Pharmacotherapy

• Without CAD/post-MI: Start ACE inhibitor (lisinopril 2.5 mg daily or trandolapril 2 mg three times weekly) OR ARB 1, 2, 4, 5
• With CAD/post-MI: Start beta-blocker (atenolol three times weekly after dialysis) 1, 2, 8

Step 3: Add Second Agent

• If BP remains >140/90 mm Hg predialysis, add calcium channel blocker (amlodipine) 1, 2, 3

Step 4: Add Third Agent

• If still uncontrolled, add the remaining class not yet used (ACE inhibitor/ARB, beta-blocker, or calcium channel blocker) 1, 2

Step 5: Resistant Hypertension Evaluation

• Definition: BP >140/90 mm Hg after achieving dry weight with three-drug regimen at near-maximal doses 1, 2
• Evaluate for secondary causes: renal artery stenosis, obstructive sleep apnea, primary hyperaldosteronism, medication/substance interference 2
• Consider minoxidil if no secondary cause identified 1
• If minoxidil fails, consider switching to continuous ambulatory peritoneal dialysis (CAPD) 1, 2
• Last resort: surgical or embolic bilateral nephrectomy 1, 2

Critical Dosing Considerations

Dialyzability Matters

• Dialyzable medications (atenolol, lisinopril): Can be dosed three times weekly after hemodialysis for directly observed therapy, which improves adherence and BP control 7, 5, 9
• Non-dialyzable medications (benazepril, fosinopril, amlodipine): Maintain more consistent drug levels but require daily dosing 2, 9

Target Blood Pressure

• Predialysis BP goal: <140/90 mm Hg (sitting position) without substantial orthostatic hypotension or symptomatic intradialytic hypotension 1, 2, 3
• This target minimizes left ventricular hypertrophy and death 1

Common Pitfalls to Avoid

• Never initiate or escalate antihypertensives without first optimizing volume status—most dialysis hypertension is volume-mediated 2, 10
• Avoid using diuretics—they are ineffective in ESRD patients 7
• Do not use standard hypertension guidelines—dialysis patients require different targets and strategies 10
• Watch for hyperkalemia with ACE inhibitors/ARBs and non-selective beta-blockers, especially during fasting or exercise 7
• Avoid ACE inhibitors with AN69 dialysis membranes due to risk of anaphylactoid reactions 7
• Monitor for intradialytic hypotension—if this occurs, consider switching to dialyzable medications dosed after dialysis 9