What is the recommended treatment for hypertension in a patient with end-stage kidney disease (ESKD)?

From the Guidelines

The recommended treatment for hypertension in patients with end-stage kidney disease (ESKD) should prioritize the use of ACE inhibitors or angiotensin receptor blockers (ARBs) as first-line agents, given their potential to reduce mortality and left ventricular hypertrophy (LVH) in these patients. When managing hypertension in ESKD patients, it's crucial to consider the complexities of their condition, including fluid overload and the need for careful fluid management through dialysis to achieve the patient's dry weight [ 1 ]. Key aspects of treatment include:

• Lifestyle modifications, such as salt restriction, to help manage blood pressure
• The use of ACE inhibitors or ARBs, which have been associated with decreased mortality in observational studies [ 1 ]
• Potential addition of other antihypertensive agents, such as calcium channel blockers or beta-blockers, to achieve target blood pressure goals
• Close monitoring of blood pressure both at home and during dialysis sessions to adjust treatment as necessary
• Consideration of the timing of medication administration in relation to dialysis sessions to prevent intradialytic hypotension. Given the complexity of hypertension management in ESKD, a multifaceted approach that includes both lifestyle changes and pharmacological intervention, tailored to the individual patient's needs and response, is essential for optimizing outcomes in terms of morbidity, mortality, and quality of life [ 1 ].

From the FDA Drug Label

The RENAAL study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3.0 mg/dL in females or males ≤60 kg and 1.5 to 3. 0 mg/dL in males >60 kg and proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]). Treatment with losartan resulted in a 16% risk reduction in the primary endpoint of doubling of serum creatinine, end-stage renal disease (ESRD) (need for dialysis or transplantation), or death. The mean baseline blood pressures were 152/82 mmHg for losartan plus conventional antihypertensive therapy and 153/82 mmHg for placebo plus conventional antihypertensive therapy At the end of the study, the mean blood pressures were 143/76 mmHg for the group treated with losartan and 146/77 mmHg for the group treated with placebo.

The recommended treatment for hypertension in a patient with end-stage kidney disease (ESKD) is losartan, as it has been shown to reduce the risk of doubling of serum creatinine, ESRD, and death by 16% in patients with type 2 diabetes and nephropathy 2.

• Losartan should be used in conjunction with conventional antihypertensive therapy to achieve a blood pressure goal of less than 140/90 mmHg.
• The dosage of losartan should be adjusted based on the patient's response to therapy, with a typical dose of 50-100 mg once daily.
• Losartan has been shown to be effective in reducing blood pressure and proteinuria in patients with hypertension and kidney disease 2.

From the Research

Treatment of Hypertension in End-Stage Kidney Disease

The treatment of hypertension in patients with end-stage kidney disease (ESKD) is crucial to reduce the risk of cardiovascular disease and mortality.

• The management of blood pressure in ESRD is complicated by factors such as missed dialysis treatments, intradialytic changes in blood pressure, medication removal with dialysis, and poor correlation of blood pressures obtained in the dialysis unit with those at home and with cardiovascular outcomes 3.
• 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 3.

Antihypertensive Medications

• Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers are reasonable first-line agents for most patients with ESKD 3.
• ACE inhibitors and ARBs exert cardioprotective effects that are independent of blood pressure reduction 3.
• Medications that are removed with dialysis may be preferred in patients who are prone to develop intradialytic hypotension 3.
• Thiazide or thiazide-like diuretics, such as hydrochlorothiazide or chlorthalidone, are also effective in treating hypertension in patients with ESKD 4.

Lifestyle Modifications

• Lifestyle modifications, including weight loss, healthy dietary pattern, physical activity, and moderation or elimination of alcohol consumption, are essential in managing hypertension in patients with ESKD 4.
• Dietary sodium restriction is often overlooked but can improve blood pressure control, especially among patients treated with an agent to block the renin-angiotensin system 5.

Blood Pressure Targets

• The blood pressure target for patients with ESKD is generally <130/80 mmHg 6, 5.
• An intensive blood pressure goal <130/80 mmHg has been recommended for patients with chronic kidney disease, including those with ESKD 6, 5.

Novel Developments

• Emerging agents, such as the non-steroidal mineralocorticoid receptor antagonist ocedurenone, dual endothelin receptor antagonist aprocitentan, and the aldosterone synthase inhibitor baxdrostat, offer novel targets and strategies to control blood pressure better 5.
• Larger and longer-term clinical trials are needed to demonstrate the safety and efficacy of these novel therapies in the future 5.