How to manage severe uncontrolled hypertension in a patient with End-Stage Renal Disease (ESRD)?

From the Guidelines

Managing severe uncontrolled hypertension in ESRD patients requires a multifaceted approach focusing on both pharmacological and non-pharmacological interventions, with the primary goal of reducing morbidity, mortality, and improving quality of life. The most recent and highest quality study, 1, suggests that in patients with ESRD under dialysis, lowering systolic blood pressure (SBP) and diastolic blood pressure (DBP) can reduce cardiovascular events, cardiovascular death, and all-cause mortality.

Key Considerations

• Optimizing dialysis prescription to achieve appropriate dry weight through ultrafiltration is crucial, as volume overload is a primary contributor to hypertension in these patients.
• Pharmacological management should include:
  • Calcium channel blockers like amlodipine (5-10 mg daily) as first-line treatment, due to their effectiveness and minimal impact on reduced kidney function.
  • ACE inhibitors or ARBs (such as lisinopril 2.5-10 mg daily or losartan 25-50 mg daily) used cautiously while monitoring potassium levels.
  • Beta-blockers like metoprolol (25-100 mg twice daily) for patients with concurrent cardiovascular disease.
• For resistant hypertension, adding a vasodilator like minoxidil (2.5-10 mg daily) or hydralazine (25-50 mg three times daily) may be necessary.
• Diuretics have limited efficacy in ESRD but may help in patients with residual renal function.
• Medication timing is crucial, with antihypertensives administered after dialysis to prevent their removal during treatment.
• Regular blood pressure monitoring, both pre- and post-dialysis, is essential for guiding therapy adjustments.
• Dietary sodium restriction to less than 2 grams daily is critical, as sodium retention significantly contributes to hypertension in ESRD patients, as supported by 1 and 1.

Additional Recommendations

• Reducing proteinuria is a therapeutic target, with RAS blockade being more effective in reducing albuminuria than other antihypertensive agents, as indicated in 1.
• Combination therapy, including RAS blockers with other antihypertensive agents, is usually required to achieve blood pressure targets.
• Loop diuretics should replace thiazides if serum creatinine is 1.5 mg/dL or eGFR is <30 mL/min/1.73 m2, as suggested in 1.

From the FDA Drug Label

The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria

Management of Severe Uncontrolled Hypertension in ESRD Patient:

• Amlodipine can be used in patients with renal impairment, including those with End-Stage Renal Disease (ESRD), without significant changes in pharmacokinetics.
• The initial dose of amlodipine may be the same as for patients with normal renal function.
• However, it is essential to monitor the patient's blood pressure and renal function closely, as the response to amlodipine may vary.
• Hydralazine may also be considered, but its use requires caution in patients with suspected coronary artery disease, cerebral vascular accidents, or advanced renal damage 2, 3.

From the Research

Management of Severe Uncontrolled Hypertension in ESRD Patients

• The management of blood pressure (BP) in End-Stage Renal Disease (ESRD) is complicated by factors such as missed dialysis treatments, intradialytic changes in BP, medication removal with dialysis, and poor correlation of BPs obtained in the dialysis unit with those at home and with CV outcomes 4.
• Control of extracellular volume with ultrafiltration and dietary sodium restriction represents the principal strategy to manage hypertension in ESRD, and antihypertensive medications are subsequently added if this strategy is inadequate 4.
• Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers are reasonable first-line agents for most patients with severe uncontrolled hypertension in ESRD 5, 4.
• Medications that are removed with dialysis may be preferred in patients who are prone to develop intradialytic hypotension, and intradialytic hypertension can be managed by challenging the patient's dry weight and using nondialyzable medications 4.
• Intensive hemodialysis (HD) reduces blood pressure and the need for oral medications indicated for hypertension, and may be a useful approach in managing severe uncontrolled hypertension in ESRD patients 6.

Antihypertensive Medications

• ACE inhibitors and ARBs exert cardioprotective effects that are independent of BP reduction, and may decrease morbidity and mortality by reducing the mean arterial pressure (MAP), aortic pulse wave velocity, and aortic systolic pressure augmentation, as well as left ventricular hypertrophy (LVH) and probably reduction of C-reactive protein (CRP) and oxidant stress 5.
• Beta-blockers decrease not only mortality, blood pressure (BP), and ventricular arrhythmias, but also improve left ventricular function in ESRD patients, and nonselective beta-blockers can cause an increase in serum potassium (particularly during fasting or exercise) 5.
• Calcium channel blockers are also associated with lower total and cardiovascular-specific mortality in HD patients, and minoxidil is a very potent vasodilator that is generally reserved for dialysis patients with severe hypertension 5.
• Transdermal clonidine therapy once a week may be beneficial for hypertensive dialysis patients who are noncompliant with their medications 5.

Special Considerations

• The majority of dialysis patients need a combination of several antihypertensive drugs for adequate BP control, and the use of multiple antihypertensive drugs is often necessary to achieve effective blood pressure control in dialysis patients 5, 7.
• Physicians treating hypertension in dialysis patients should be familiar with the pharmacokinetic properties of antihypertensive drugs in renal failure and choose the dosages accordingly, and vigorous control of hypertension is recommended to reduce the disease burden in patients with ESRD 7.
• Renal transplant may be considered as a final therapeutic modality for patients with severe uncontrolled hypertension in ESRD, as it can help to control blood pressure and reduce the need for antihypertensive medications 8.