What are the recommended antihypertensive medications for a patient with end-stage renal disease (ESRD) undergoing hemodialysis, particularly those that are dialysable and nondialysable?

Dialysable Antihypertensives in Hemodialysis Patients

The choice between dialyzable and non-dialyzable antihypertensives should be guided primarily by intradialytic blood pressure patterns: avoid non-dialyzable agents in patients with frequent intradialytic hypotension, while preferring non-dialyzable agents for patients with intradialytic hypertension or stable intradialytic blood pressure. 1

Understanding Dialyzability and Clinical Implications

Dialyzable Beta-Blockers

• Atenolol and metoprolol are highly dialyzable and removed during hemodialysis sessions 1
• Acebutolol is also dialyzable 2
• These agents may be preferred in patients experiencing frequent intradialytic hypotension, as their removal during dialysis reduces the risk of excessive blood pressure lowering during the procedure 1
• Critical caveat: One retrospective study found that dialyzable beta-blockers (atenolol, metoprolol) were NOT associated with lower mortality risk, possibly due to loss of intradialytic protection against arrhythmias when the drug is removed 1

Non-Dialyzable Beta-Blockers

• Propranolol and carvedilol are non-dialyzable and maintain therapeutic levels throughout dialysis 1
• Non-dialyzable beta-blockers were associated with lower mortality risk in one retrospective study, attributed to preserved intradialytic arrhythmia protection 1
• Major pitfall: Carvedilol showed higher mortality rates versus metoprolol in another study due to increased intradialytic hypotension risk 1
• Avoid non-dialyzable agents in patients with frequent intradialytic hypotension 1

Other Antihypertensive Classes by Dialyzability

Non-dialyzable agents (levels unchanged during dialysis):

• Clonidine 1
• Labetalol 1
• All calcium channel blockers 1
• All angiotensin receptor blockers (ARBs) 1
• Benazepril and fosinopril (ACE inhibitors) 1

Dialyzable agents (removed during dialysis):

• Enalapril and ramipril (ACE inhibitors) 1
• Methyldopa 1
• Nadolol 1
• Minoxidil 1
• Nitroprusside 1

Important uncertainty: Bisoprolol was previously considered non-dialyzable but recent evidence suggests it may actually be dialyzable, highlighting that dialyzability data contains uncertainties 1

Clinical Decision Algorithm

Step 1: Assess Intradialytic Blood Pressure Pattern

For patients with frequent intradialytic hypotension:

• Prioritize dialyzable agents (atenolol, metoprolol, enalapril) to minimize hypotension risk during dialysis 1
• Consider administering medications after dialysis rather than before 1
• However, weigh this against potential loss of arrhythmia protection during dialysis 1

For patients with intradialytic hypertension (BP rise >10 mmHg pre- to post-dialysis):

• Prioritize non-dialyzable agents (propranolol, carvedilol, all calcium channel blockers, ARBs) to maintain therapeutic levels throughout dialysis 1
• These patients require continuous blood pressure control that persists during the dialysis session 1

For patients with stable intradialytic blood pressure:

• Use longer-acting, once-daily non-dialyzable medications to improve adherence and reduce pill burden 1
• This approach is reasonable when intradialytic hypotension is not a concern 1

Step 2: Select First-Line Agent Based on Comorbidities

ACE inhibitors or ARBs (first-line for most patients):

• Reduce left ventricular mass index independent of blood pressure reduction 1
• May preserve residual kidney function, especially critical in peritoneal dialysis patients 1
• ARBs are all non-dialyzable 1
• Among ACE inhibitors: benazepril and fosinopril are non-dialyzable; enalapril and ramipril are dialyzable 1

Beta-blockers (first-line for patients with coronary artery disease or heart failure):

• Strongest evidence for reducing cardiovascular mortality in dialysis patients 1
• Choose based on dialyzability considerations above 1

Calcium channel blockers (all non-dialyzable):

• Associated with decreased total and cardiovascular mortality in observational studies 1
• Amlodipine specifically reduced cardiovascular events in randomized trials of hemodialysis patients 3
• Reasonable first-line choice for patients without specific cardiovascular indications 3

Step 3: Optimize Dosing Strategy

For dialyzable agents:

• Can be dosed thrice-weekly immediately after dialysis in non-adherent patients 4, 5
• This supervised administration strategy is particularly effective for lisinopril and atenolol 6, 5
• Atenolol dosing in renal impairment: 50 mg daily for creatinine clearance 15-35 mL/min; 25 mg daily for creatinine clearance <15 mL/min 7
• Patients on hemodialysis should receive atenolol 25-50 mg after each dialysis under hospital supervision due to risk of marked blood pressure falls 7

For non-dialyzable agents:

• Administer preferentially at night to control nocturnal blood pressure surge and minimize intradialytic hypotension 3, 5
• Once-daily dosing improves adherence 1, 5

Critical Pitfalls to Avoid

• Never initiate or escalate antihypertensive medications without first optimizing volume status through ultrafiltration and sodium restriction (2-3 g/day), as volume overload underlies most hypertension in dialysis patients 1, 3
• Do not routinely withhold all antihypertensives before dialysis, as this worsens interdialytic blood pressure control and may increase cardiac arrhythmia risk 8
• Avoid using non-dialyzable agents (especially carvedilol) in patients with recurrent intradialytic hypotension, as they maintain therapeutic levels during dialysis and increase hypotension risk 1
• Do not assume all beta-blockers within a class have the same dialyzability—there is large variability even within medication classes 4
• Recognize that older dialyzability data may be inaccurate (e.g., bisoprolol), so monitor clinical response carefully 1

When Medications Are Insufficient

• If blood pressure remains uncontrolled despite achieving dry weight and using three antihypertensive agents from different classes, evaluate for secondary causes of resistant hypertension 1
• Consider minoxidil for severe resistant hypertension 1
• If minoxidil fails, consider transition to continuous ambulatory peritoneal dialysis (CAPD) 1
• Surgical or embolic nephrectomy is a last resort if CAPD proves ineffective 1