Are beta blockers (beta-adrenergic blocking agents) dialysable in patients with impaired renal function?

Beta Blocker Dialyzability in Patients with Impaired Renal Function

Beta blockers have varying degrees of dialyzability, with atenolol, nadolol, practolol, and sotalol being highly dialyzable, while betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol are not dialyzable in patients with impaired renal function. 1

Classification of Beta Blockers by Dialyzability

Based on the most recent and comprehensive evidence, beta blockers can be categorized as follows:

Highly Dialyzable

• Atenolol
• Nadolol
• Practolol
• Sotalol

Moderately Dialyzable

• Acebutolol
• Bisoprolol
• Metipranolol

Slightly Dialyzable

• Metoprolol
• Talinolol

Not Dialyzable

• Betaxolol
• Carvedilol
• Labetalol
• Mepindolol
• Propranolol
• Timolol

Clinical Implications of Beta Blocker Dialyzability

Impact on Efficacy and Dosing

• Dialyzable beta blockers may require post-dialysis supplemental dosing to maintain therapeutic levels 1, 2
• The relative impact of dialysis on total clearance increases as kidney function declines, especially for highly dialyzable agents like atenolol 1
• For example, hemodialysis clearance of 120 mL/min represents 46% of total clearance for atenolol in normal kidney function but 86% in anuric patients 1

Clinical Outcomes

• Evidence suggests that dialyzability may affect mortality outcomes in hemodialysis patients
• A study of older hemodialysis patients found that initiation of high-dialyzability beta blockers (atenolol, acebutolol, metoprolol) was associated with a 40% higher risk of death compared to low-dialyzability agents (bisoprolol, propranolol) 3
• However, contradictory evidence exists, with a larger Taiwanese study showing lower mortality and cardiovascular events with dialyzable beta blockers 4

Specific Beta Blocker Properties and Dialyzability

Highly Dialyzable Agents

• Atenolol: Dialytic clearance of 72-167 mL/min depending on measurement method 5
  • Undergoes little hepatic metabolism with 85% of IV dose excreted in urine within 24 hours 6
  • Half-life significantly prolonged in renal failure 6

Moderately/Slightly Dialyzable Agents

• Metoprolol: Dialytic clearance of 87-114 mL/min 5
  • Primarily metabolized by CYP2D6 in the liver 7
  • Only about 10% of an IV dose is excreted unchanged in urine for extensive metabolizers 7
  • Bisoprolol: Dialytic clearance of 44-96 mL/min 5

Non-Dialyzable Agents

• Carvedilol: Minimal dialytic clearance (0.2-24 mL/min) 5
• Propranolol: Not meaningfully removed by dialysis due to high endogenous clearance and large volume of distribution 1

Recommendations for Beta Blocker Selection in Dialysis Patients

1. For patients requiring dialysis with cardiovascular indications:

   • Non-dialyzable agents (carvedilol, propranolol) are preferred to maintain consistent therapeutic levels 2
   • Carvedilol is particularly preferred in patients with heart failure with reduced ejection fraction 2, 8

2. If using dialyzable beta blockers:

   • Administer post-dialysis to maintain therapeutic levels 2
   • Consider that supplemental dosing may be required after dialysis sessions 1

3. For patients with intradialytic blood pressure concerns:

   • Avoid beta blockers in patients with intradialytic hypotension associated with bradycardia 8
   • Non-dialyzable agents may be preferred for patients with stable intradialytic blood pressure 2

Practical Considerations

• The dialyzability of beta blockers is independent of kidney function, but its relative impact compared to total body clearance increases as kidney function declines 1
• Modern high-flux dialysis membranes may have different clearance characteristics than older membranes, affecting previously established dialyzability data 5
• When selecting a beta blocker for a dialysis patient, consider both the dialyzability and the specific cardiovascular indication (hypertension, heart failure, coronary artery disease) 2, 9

By understanding the dialyzability characteristics of different beta blockers, clinicians can make more informed decisions to optimize therapeutic efficacy and minimize adverse outcomes in patients with impaired renal function requiring dialysis.