What ACE (Angiotensin-Converting Enzyme) inhibitor is recommended for a dialysis patient with hypertension and orthostatic hypotension?

ACE Inhibitor Selection for Dialysis Patients with Orthostatic Hypotension

Fosinopril is the preferred ACE inhibitor for dialysis patients, particularly when orthostatic hypotension is present, because it is not removed by dialysis and maintains stable blood levels between sessions. 1, 2

Why Fosinopril is Optimal in This Clinical Scenario

Pharmacokinetic Advantages in Dialysis

• Fosinopril undergoes dual hepatobiliary and renal elimination, preventing drug accumulation even in end-stage renal disease (ESRD). 2
• Unlike enalapril, ramipril, captopril, lisinopril, and perindopril—which are substantially removed during hemodialysis—fosinopril levels remain stable and do not require post-dialysis supplementation. 3, 2
• This non-dialyzability is actually advantageous for patients with orthostatic hypotension, as it prevents the precipitous blood pressure drops that can occur when dialyzable ACE inhibitors are removed during treatment. 3, 4

Specific Benefits for Orthostatic Hypotension

• ACE inhibitors as a class have minimal impact on orthostatic blood pressure compared to other antihypertensive agents. 5
• The European Society of Cardiology recommends RAS inhibitors (ACE inhibitors or ARBs) as first-line agents with minimal impact on orthostatic blood pressure. 5
• Fosinopril's stable pharmacokinetics prevent the intradialytic and post-dialytic hypotension that commonly occurs with dialyzable ACE inhibitors. 3, 1

Alternative ACE Inhibitors (If Fosinopril Unavailable)

Second Choice: Benazepril

• Benazepril is not significantly removed by hemodialysis, making it another reasonable option. 3
• However, it lacks the extensive hepatobiliary elimination pathway that makes fosinopril uniquely suited for ESRD. 2

Avoid These ACE Inhibitors in Dialysis Patients

• Do not use enalapril, captopril, lisinopril, ramipril, or perindopril as they are substantially cleared during dialysis, requiring supplemental dosing and increasing risk of hypotensive episodes. 3, 2, 6
• These agents show high accumulation rates between dialysis sessions and excessive removal during dialysis, creating a "roller coaster" effect on blood pressure. 2

Critical Management Considerations

Dosing Strategy

• Start fosinopril at low doses (5-10 mg daily) and titrate gradually while monitoring for orthostatic symptoms. 5
• No dose adjustment is required based on dialysis schedule since fosinopril is not dialyzed. 2
• Monitor blood pressure in both sitting and standing positions (after 5 minutes sitting, then at 1 and 3 minutes after standing) to assess orthostatic response. 5

Volume Status is Paramount

• Before initiating or adjusting ACE inhibitor therapy, ensure the patient is at appropriate dry weight. 3
• Volume depletion from aggressive ultrafiltration can exacerbate orthostatic hypotension and should be corrected before ACE inhibitor initiation. 1, 7
• The K/DOQI guidelines emphasize that achievement of dry weight and reduction of extracellular fluid volume should be pursued as the primary strategy for blood pressure control in dialysis patients. 3

Monitoring for Anaphylactoid Reactions

• ACE inhibitors carry a specific risk of anaphylactoid reactions during dialysis with high-flux membranes. 1
• This risk applies to all ACE inhibitors, including fosinopril, and patients should be monitored during the first several dialysis sessions after initiation. 1, 6
• If anaphylactoid reactions occur, consider switching to an angiotensin receptor blocker (ARB), which does not cause this complication. 6

Common Pitfalls to Avoid

Don't Assume All ACE Inhibitors Are Equivalent in Dialysis

• The substantial differences in dialyzability between ACE inhibitors make drug selection critically important in this population. 3, 2
• Using a dialyzable ACE inhibitor without appropriate dose adjustment and timing can lead to both inadequate blood pressure control and symptomatic hypotension. 4, 2

Don't Attribute Hypotension Solely to the ACE Inhibitor

• In dialysis patients with orthostatic hypotension on ACE inhibitors, first evaluate for volume depletion, anemia, autonomic dysfunction, and other contributing medications before discontinuing the ACE inhibitor. 5, 7
• The case report of a CAPD patient demonstrates that chronic hypovolemia can cause both accelerated hypertension and orthostatic hypotension simultaneously, which improved with volume correction and low-dose captopril. 7

Don't Combine with Other High-Risk Medications

• Avoid concurrent use of alpha-blockers (doxazosin, prazosin, terazosin), which are strongly associated with orthostatic hypotension in dialysis patients. 5
• Beta-blockers should generally be avoided unless there are compelling indications (prior MI, heart failure with reduced ejection fraction). 5

Supporting Evidence for ACE Inhibitors in Dialysis

Mortality Benefit

• Observational studies demonstrate that ACE inhibitor use is associated with decreased mortality in CKD Stage 5 patients. 3
• The K/DOQI guidelines recommend ACE inhibitors or ARBs as first-line treatment for hypertension in dialysis patients based on their cardioprotective effects beyond blood pressure reduction. 3

Heart Failure Management

• For dialysis patients with heart failure and reduced ejection fraction, ACE inhibitors improve survival despite the lack of large randomized trials specifically in the dialysis population. 3
• Dosing schedules may need individualization around dialysis sessions to avoid intradialytic hypotension, which is another reason fosinopril's non-dialyzability is advantageous. 3