What is the recommended pharmacological regimen for a patient with end-stage renal disease (ESRD) and hypertension, with or without a history of myocardial infarction (MI) or coronary artery disease (CAD), undergoing hemodialysis?

Pharmacological Regimen for ESRD Patients on Hemodialysis with Hypertension

Initial Management: Volume Control is Paramount

Before initiating or escalating antihypertensive medications, you must first optimize volume status through dialysis prescription adjustments and sodium restriction, as volume overload is the primary driver of hypertension in this population. 1, 2

• Target predialysis blood pressure should be <140/90 mmHg measured in the sitting position, while avoiding substantial orthostatic hypotension or symptomatic intradialytic hypotension 1, 2
• Restrict dietary sodium to 2-3 g/day with intensive patient education 1
• Gradually probe and adjust target dry weight to achieve true euvolemia 1
• Consider increasing dialysis treatment time and/or frequency if volume control remains inadequate 1, 3

First-Line Pharmacological Agents

For Patients WITH Previous MI or Established CAD:

Beta-blockers are the preferred first-line agent, as they demonstrate the strongest evidence for reducing cardiovascular mortality and heart failure hospitalizations in this high-risk population. 4, 1, 2

Specific beta-blocker selection and dosing:

• Carvedilol 6.25-25 mg twice daily (non-dialyzable; preferred for stable intradialytic BP) 1, 5
• Atenolol 25-100 mg after each dialysis session (dialyzable; preferred for patients with frequent intradialytic hypotension) 1, 5, 6
• Metoprolol succinate 50-200 mg once daily (minimally dialyzable) 4, 5

For Patients WITHOUT Specific Cardiovascular Indications:

ACE inhibitors or ARBs should be initiated as first-line therapy, as they reduce left ventricular hypertrophy and have been associated with decreased mortality in observational studies. 4, 1, 2

Specific ACE inhibitor/ARB selection and dosing:

• Lisinopril 5-40 mg after each dialysis session (renally eliminated; allows thrice-weekly supervised dosing) 5, 7, 6
• Benazepril 5-20 mg daily (not significantly removed by dialysis) 8, 5
• Losartan 25-100 mg daily (ARB alternative; not removed by dialysis) 5, 9
• Irbesartan 75-300 mg daily (ARB alternative; not removed by dialysis) 5

Critical caveat: Avoid ACE inhibitors in patients dialyzed with polyacrylonitrile (AN69) membranes due to risk of life-threatening anaphylactoid reactions 2, 8, 5

Second-Line Agents for Uncontrolled Hypertension

If blood pressure remains >140/90 mmHg after optimizing volume status and initiating first-line therapy, add a calcium channel blocker as the second agent. 1, 2

Specific calcium channel blocker dosing:

• Amlodipine 5-10 mg once daily (demonstrated reduction in cardiovascular events in randomized trials) 1, 3, 5
• Nifedipine extended-release 30-90 mg once daily 5, 9
• Diltiazem extended-release 120-360 mg once daily (non-dihydropyridine option) 5

Medication Timing Strategy

Administer all antihypertensive medications preferentially at night (bedtime) to reduce nocturnal blood pressure surge and minimize intradialytic hypotension. 1, 2, 3

• Exception: Dialyzable agents like lisinopril and atenolol should be given after each dialysis session (thrice weekly) to enhance compliance in non-adherent patients 5, 7, 6

Management of Resistant Hypertension

Resistant hypertension is defined as BP >140/90 mmHg despite achieving dry weight and using three appropriate antihypertensive agents from different classes. 2

Algorithmic approach:

1. Re-evaluate and challenge dry weight more aggressively 2, 3
2. Add minoxidil 2.5-40 mg twice daily as a potent vasodilator for severe resistant hypertension 2, 5
3. If hypertension remains uncontrolled after minoxidil trial, consider switching to peritoneal dialysis 2
4. If peritoneal dialysis proves ineffective, surgical or embolic nephrectomy may be considered as last resort 2

Special Considerations for Preserving Residual Kidney Function

For patients with significant residual urine output (>100 mL/day), preferentially use ACE inhibitors or ARBs, as these agents slow the decline in residual kidney function, particularly in peritoneal dialysis patients. 1, 2

• Add loop diuretics (furosemide 40-240 mg daily or bumetanide 1-10 mg daily) to increase urine output in patients with substantial residual renal function 4, 2

Critical Pitfalls to Avoid

• Never initiate or escalate antihypertensive medications without first assessing and optimizing volume status through dialysis adjustments 1, 2
• Avoid aggressive blood pressure lowering in elderly patients with isolated systolic hypertension, as this may increase mortality risk 2
• Do not use ACE inhibitors with AN69 dialysis membranes 2, 8, 5
• Monitor for hyperkalemia when using ACE inhibitors/ARBs, particularly in patients with residual kidney function or those receiving potassium-sparing diuretics 8, 9
• Avoid administering long-acting antihypertensive medications before dialysis sessions, as this increases risk of intradialytic hypotension 1, 6

Monitoring Parameters

• Predialysis and postdialysis blood pressure at each session 1, 2
• Home blood pressure monitoring if systolic BP rises >10 mmHg from pre- to post-dialysis in ≥4 of 6 consecutive treatments 1
• Serum potassium levels periodically when using ACE inhibitors/ARBs 8, 9
• Assess for orthostatic hypotension and intradialytic hypotension symptoms 1, 2
• Evaluate residual urine output to guide diuretic and ACE inhibitor/ARB use 4, 2