How to manage resistant hypertension in patients on dialysis?

Management of Resistant Hypertension in Dialysis Patients

In dialysis patients with resistant hypertension, prioritize achieving true dry weight through strict sodium restriction (<1500 mg/day), low-sodium dialysate, and intensified ultrafiltration before escalating pharmacotherapy, as volume overload is the primary driver of treatment resistance in this population. 1

Define and Confirm True Resistant Hypertension

Before intensifying treatment, you must exclude pseudoresistance:

• Resistant hypertension in dialysis is defined as BP >140/90 mmHg despite adherence to three antihypertensive agents at maximal tolerated doses (including a RAS blocker, long-acting calcium channel blocker, and diuretic appropriate for kidney function) after achieving dry weight. 1

• Confirm true hypertension with 44-hour interdialytic ambulatory BP monitoring or home BP monitoring to exclude white-coat effect. 1, 2

• Verify medication adherence through direct observation or drug level testing, as nonadherence is a major cause of apparent resistance. 1, 2

• Ensure proper BP measurement technique with sitting position and appropriate cuff size. 1

Step 1: Aggressive Volume Management (The Critical First Step)

Volume overload is the most important treatable cause of resistant hypertension in dialysis patients and must be addressed before adding more medications. 1, 2

• Implement strict dietary sodium restriction with counseling emphasizing <1500 mg/day. 1

• Use low-sodium dialysate to optimize volume status. 1

• Probe for true dry weight through gradual ultrafiltration intensification, even if this causes transient intradialytic symptoms. 1

• Ensure adequate dialysis time of at least 4 hours to deliver adequate dialysis dose and facilitate dry weight achievement. 2

Common pitfall: Clinicians often escalate antihypertensive medications without adequately addressing volume status, which leads to treatment failure. 2

Step 2: Optimize Three-Drug Regimen

Once volume status is optimized, ensure the patient is on the correct three-drug combination:

• Start with ACE inhibitors (benazepril, fosinopril) or ARBs as first-line therapy, as they reduce left ventricular hypertrophy and are associated with decreased mortality in dialysis patients. 1

• Choose non-dialyzable ACE inhibitors (benazepril, fosinopril) over dialyzable ones (enalapril, ramipril) to maintain consistent drug levels throughout the dialysis cycle. 1, 3

• Add beta-blockers (carvedilol, labetalol, bisoprolol) particularly if the patient has prior myocardial infarction or coronary artery disease, as they are associated with decreased mortality in CKD. 1, 4

• Add long-acting dihydropyridine calcium channel blockers (amlodipine) as they are associated with decreased total and cardiovascular mortality in observational studies. 1

Important consideration: Avoid dialyzable antihypertensive medications as their removal during dialysis can cause paradoxical BP elevation during and after dialysis sessions. 3

Step 3: Add Mineralocorticoid Receptor Antagonist

If BP remains uncontrolled on the optimized three-drug regimen:

• Add low-dose spironolactone to existing treatment as the preferred fourth agent. 4

• If spironolactone is not tolerated, substitute eplerenone or add amiloride. 4

• Monitor serum potassium closely, as hyperkalemia risk is elevated in dialysis patients on RAS blockers and MRAs. 5

Step 4: Additional Agents for Refractory Cases

If BP remains uncontrolled after adding an MRA:

• Add bisoprolol (if not already on a beta-blocker) or doxazosin as the next step. 4

• Consider hydralazine 25 mg three times daily, titrating upward to maximum dose. 4

• For severe refractory cases, consider minoxidil 2.5 mg two to three times daily (requires concomitant beta-blocker and loop diuretic). 4

Step 5: Evaluate for Secondary Causes

If BP remains uncontrolled despite dialysis optimization plus three to four antihypertensive agents, evaluate for secondary causes including renal artery stenosis, obstructive sleep apnea, primary hyperaldosteronism, and medication/substance interference. 1

Step 6: Last Resort Options

For truly refractory cases:

• Consider switching from hemodialysis to continuous ambulatory peritoneal dialysis (CAPD) for better volume control. 1

• Surgical or embolic bilateral nephrectomy may be considered as a last resort. 1

• Catheter-based renal denervation may be considered at medium-to-high volume centers after shared risk-benefit discussion and multidisciplinary assessment. 4

Target Blood Pressure

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

• The 2024 ESC guidelines suggest considering an SBP target range of 120-130 mmHg in general hypertensive populations, but this has not been specifically validated in dialysis patients. 4

Critical Pitfalls to Avoid

• Do not escalate antihypertensive medications without first optimizing volume status through sodium restriction and ultrafiltration. 1, 2

• Avoid excessive BP reduction during dialysis, as intradialytic hypotension can accelerate loss of residual kidney function and increase cardiovascular risk. 6

• Do not use dialyzable antihypertensive agents, as they will be removed during dialysis sessions causing inconsistent BP control. 1, 3

• Be cautious with ACE inhibitors/ARBs regarding hyperkalemia risk, especially when combined with MRAs. 5

• Recognize that 67% of dialysis patients with true resistant hypertension have no fluid overload, so volume management alone will not solve all cases. 7