What are the recommended medications for managing hypertension in patients with End-Stage Renal Disease (ESRD)?

Hypertension Management in End-Stage Renal Disease

For patients with ESRD, diuretics (particularly loop diuretics) and calcium channel blockers are the preferred first-line antihypertensive agents, as recommended by the European Society of Cardiology/Hypertension guidelines. 1

Primary Treatment Strategy

The foundation of hypertension management in ESRD differs fundamentally from the general population:

• Volume control through ultrafiltration and dietary sodium restriction (<2g/day) represents the principal strategy before adding antihypertensive medications 2, 3
• Achieving and maintaining dry weight is the most critical intervention, as volume expansion is the dominant cause of hypertension in ESRD 3
• Antihypertensive medications are added only when volume management alone is inadequate 2

Preferred Medication Classes

First-Line Agents

Diuretics and calcium channel blockers are specifically recommended for ESRD/proteinuria according to the European Society of Cardiology guidelines 1:

• Loop diuretics (not thiazides) are the appropriate diuretic class in ESRD, as thiazide diuretics lose efficacy when GFR falls below 30 mL/min 2
• Calcium channel blockers (particularly dihydropyridines like amlodipine) are associated with lower total and cardiovascular-specific mortality in hemodialysis patients 4
• These agents provide effective blood pressure control without the complications of hyperkalemia that can occur with RAS blockade 4

Second-Line Agents

ACE inhibitors, ARBs, and beta-blockers are reasonable alternatives when first-line agents are insufficient 2, 5:

• ACE inhibitors and ARBs offer cardioprotective effects independent of blood pressure reduction, including reduction of left ventricular hypertrophy, aortic pulse wave velocity, and possibly C-reactive protein 4, 5
• Beta-blockers decrease mortality, blood pressure, and ventricular arrhythmias while improving left ventricular function in ESRD patients 4
• Both ACE inhibitors/ARBs and beta-blockers carry specific risks in ESRD that must be monitored 4

Critical ESRD-Specific Considerations

Medication Selection Based on Dialyzability

Choose medications based on whether they are removed by dialysis, as this affects both efficacy and safety 2, 4:

• Dialyzable medications (lisinopril, atenolol) may be preferred in patients prone to intradialytic hypotension, as they can be dosed thrice-weekly after dialysis sessions 2, 4
• Non-dialyzable medications are preferred for managing intradialytic hypertension 2
• Thrice-weekly supervised administration after hemodialysis of dialyzable agents like lisinopril and atenolol can enhance blood pressure control and improve adherence 4

Monitoring for Complications

Monitor closely for hyperkalemia when using ACE inhibitors or ARBs in ESRD patients 4:

• Risk of hyperkalemia is significantly elevated in ESRD, particularly with RAS blockade 4
• ACE inhibitors carry additional risk of anaphylactoid reactions when used with AN69 dialysis membranes 4
• Both ACE inhibitors and ARBs may aggravate renal anemia 4
• Nonselective beta-blockers can increase serum potassium, particularly during fasting or exercise 4

Treatment Algorithm for Resistant Hypertension in ESRD

When blood pressure remains uncontrolled despite volume optimization:

1. Start with a calcium channel blocker (amlodipine 5-10mg daily) 1, 4
2. Add a loop diuretic if residual urine output exists 2
3. Add an ACE inhibitor or ARB (with close potassium monitoring) for additional cardioprotection 2, 4, 5
4. Add a beta-blocker for patients with heart failure, coronary disease, or arrhythmias 4
5. Consider minoxidil for severe resistant hypertension, as it is a very potent vasodilator generally reserved for dialysis patients 4
6. Consider transdermal clonidine (once weekly) for noncompliant patients 4

Common Pitfalls to Avoid

• Do not use thiazide diuretics as they are ineffective in ESRD (GFR <30 mL/min) - use loop diuretics instead 2
• Do not assume medication failure without first optimizing dry weight through ultrafiltration and sodium restriction, as volume expansion is the primary driver of hypertension in ESRD 3
• Do not overlook dialyzability when selecting medications - this significantly impacts dosing frequency and efficacy 2, 4
• Do not rely on dialysis unit blood pressure measurements alone as they correlate poorly with home blood pressure and cardiovascular outcomes 2
• Do not use ACE inhibitors with AN69 dialysis membranes due to risk of anaphylactoid reactions 4

Practical Dosing Strategy

Most dialysis patients require combination therapy with multiple antihypertensive drugs for adequate blood pressure control 4, 5:

• Consider thrice-weekly dosing after dialysis for dialyzable medications (lisinopril, atenolol) to enhance adherence 2, 4
• This supervised dosing strategy has demonstrated robust blood pressure-lowering effects 2
• Adjust doses based on pharmacokinetic properties in renal failure 5