What is the recommended antihypertensive regimen for a patient undergoing hemodialysis?

Antihypertensive Regimen in Hemodialysis Patients

Start with volume optimization through achieving dry weight and sodium restriction, then initiate ACE inhibitors or ARBs as first-line pharmacotherapy, targeting a predialysis blood pressure of 140/90 mmHg. 1

Initial Non-Pharmacologic Management

Volume control is the cornerstone of blood pressure management in dialysis patients and must be addressed before escalating medications. 1, 2

• Achieve dry weight through ultrafiltration and continuously emphasize dietary sodium restriction (ideally <1500 mg/day) 1, 2, 3
• Use low-sodium dialysate to optimize volume status 3
• Probe for true dry weight through gradual ultrafiltration intensification, even if this causes transient intradialytic symptoms 3
• Volume overload underlies most cases of BP elevation in dialysis patients 1

Target Blood Pressure

Aim for predialysis BP <140/90 mmHg (measured sitting) without substantial orthostatic hypotension or symptomatic intradialytic hypotension. 1

• This target minimizes left ventricular hypertrophy and mortality based on the only prospective study in dialysis populations 1
• Avoid aggressive BP lowering that causes intradialytic hypotension, as this accelerates loss of residual kidney function and increases cardiovascular risk 4

First-Line Pharmacotherapy

ACE inhibitors or ARBs are recommended as first-line agents for most hemodialysis patients. 1, 2

• These agents reduce left ventricular hypertrophy in HD patients 1, 2
• ACE inhibitors are associated with decreased mortality in observational studies of ESRD patients 1, 2
• ARBs may be more potent than ACE inhibitors for LVH reduction 1, 2
• Choose non-dialyzable ACE inhibitors (benazepril, fosinopril) over dialyzable ones (enalapril, ramipril) to maintain consistent drug levels 2, 3
• Long-acting agents can be dosed once daily to improve adherence and reduce pill burden 1
• For noncompliant patients, renally eliminated agents like lisinopril can be given thrice weekly after hemodialysis under direct observation 5, 6

Critical Caveat for ACE Inhibitors

• Avoid ACE inhibitors in patients treated with polyacrylonitrile (AN69) dialysis membranes due to risk of life-threatening anaphylactoid reactions 2, 7
• Monitor for hyperkalemia, particularly with concomitant use of potassium-sparing diuretics or supplements 7

Second-Line Agents Based on Compelling Indications

Beta-blockers should be preferred in patients with previous myocardial infarction or established coronary artery disease. 1, 2

• Beta-blockers are associated with decreased mortality in CKD patients 1, 2
• Consider non-dialyzable beta-blockers (propranolol, carvedilol) over highly dialyzable ones (atenolol, metoprolol) to preserve intradialytic protection against arrhythmias 1, 2
• However, be cautious with carvedilol in patients with frequent intradialytic hypotension, as it may increase mortality risk compared to metoprolol 1

Calcium channel blockers should be added when additional agents are needed to achieve BP control. 1, 2

• Long-acting dihydropyridine CCBs (amlodipine) are preferred 3
• Observational studies suggest CCBs are associated with decreased total and cardiovascular mortality in dialysis patients 1, 2, 8
• CCB levels do not change significantly during dialysis 2

Algorithm for Medication Selection

1. Start with ACE inhibitor or ARB (benazepril, fosinopril, or any ARB) 1, 2, 3
2. Add beta-blocker if history of MI or CAD (carvedilol, labetalol, or bisoprolol) 1, 2, 3
3. Add long-acting calcium channel blocker (amlodipine) 1, 2, 3
4. Add alpha-blocker or direct vasodilator (doxazosin, hydralazine) if needed 1, 3

Management of Resistant Hypertension

Resistant hypertension is defined as BP >140/90 mmHg despite achieving dry weight and using three appropriate antihypertensive agents at near-maximal doses. 1, 3

Stepwise Approach:

1. Re-evaluate dry weight and sodium restriction before intensifying pharmacotherapy 3
2. Evaluate for secondary causes: renal artery stenosis, obstructive sleep apnea, primary hyperaldosteronism, medication/substance interference 3
3. Add spironolactone as the preferred fourth agent (if not contraindicated by hyperkalemia) 3
4. Consider minoxidil for severe refractory cases (requires concomitant beta-blocker and loop diuretic) 1, 3
5. Switch to continuous ambulatory peritoneal dialysis (CAPD) if hypertension remains uncontrolled after minoxidil trial 1, 2
6. Surgical or embolic bilateral nephrectomy as last resort if CAPD proves ineffective 1, 2, 3

Pharmacokinetic Considerations

Consider dialyzability when selecting and timing medications to avoid intradialytic hypotension or loss of BP control. 1, 2

• Non-dialyzable agents: benazepril, fosinopril, carvedilol, labetalol, all CCBs, all ARBs, clonidine 2
• Dialyzable agents: enalapril, ramipril, atenolol, metoprolol 2
• For patients with stable intradialytic BP, once-daily longer-acting medications improve adherence 1
• Timing of administration should account for interdialytic BP patterns and frequency of intradialytic hypotension 1

Common Pitfalls to Avoid

• Do not escalate antihypertensive medications without first optimizing volume status 1, 2
• Avoid using ACE inhibitors with AN69 dialysis membranes 2, 7
• Do not use short-acting agents requiring thrice-daily dosing due to high pill burden and risk of rebound hypertension from noncompliance 5
• Monitor for hyperkalemia when using ACE inhibitors, ARBs, or spironolactone 7
• Avoid excessive BP reduction that causes symptomatic intradialytic hypotension 1, 4