What is the most effective antihypertensive medication for a patient with Chronic Kidney Disease (CKD)?

From the Guidelines

For a patient with Chronic Kidney Disease (CKD), the most effective antihypertensive medication is a renin-angiotensin-system inhibitor (RASi), such as an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), as they not only lower blood pressure but also reduce protein in the urine and slow CKD progression. These medications are recommended as the first-line treatment for patients with high blood pressure and CKD, with or without diabetes, due to their ability to decrease pressure within the kidneys' filtering units and reduce the risk of cardiovascular events 1. The choice between an ACEi and an ARB should be based on individual patient characteristics, such as the presence of diabetes or albuminuria, and the specific medication should be started at a lower dose (e.g., lisinopril 2.5-5mg daily or losartan 25-50mg daily) and gradually increased as needed and tolerated. Some key points to consider when using RASi in patients with CKD include:

• Monitoring kidney function and potassium levels regularly, especially when starting or adjusting doses 1
• Avoiding combinations of ACEi, ARB, and direct renin inhibitor (DRI) therapy in patients with CKD, with or without diabetes 1
• Considering lower blood pressure targets (e.g., <130/80 mmHg) for patients with CKD, especially those with severely elevated albuminuria 1
• Adding other antihypertensive medications, such as calcium channel blockers or diuretics, if blood pressure remains uncontrolled, while using caution with diuretics in advanced CKD 1.

From the FDA Drug Label

In patients with renovascular hypertension lisinopril has been shown to be well tolerated and effective in reducing blood pressure [see Warnings and Precautions (5. 3)].

The RENAAL study involving 1513 patients treated with losartan or placebo, the overall incidences of reported adverse events were similar for the two groups. Discontinuations of losartan because of side effects were similar to placebo (19% for losartan, 24% for placebo)

The most effective antihypertensive medication for a patient with Chronic Kidney Disease (CKD) is lisinopril or losartan, as both have been shown to be effective in reducing blood pressure in patients with CKD. However, lisinopril is an ACE inhibitor and losartan is an angiotensin II receptor antagonist, and the choice between them should be based on individual patient characteristics and medical history.

• Lisinopril has been shown to be well tolerated and effective in reducing blood pressure in patients with renovascular hypertension.
• Losartan has been shown to be effective in reducing the incidence of end-stage renal disease and doubling of serum creatinine in patients with diabetic nephropathy 2 3.

From the Research

Antihypertensive Medications for CKD

The most effective antihypertensive medication for a patient with Chronic Kidney Disease (CKD) is a topic of ongoing research. Several studies have investigated the efficacy of different medications and combinations in managing CKD.

• Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs): A study published in 2017 4 found that combination therapy with ACEIs and ARBs reduced proteinuria and prevented structural lesions more effectively than either drug alone in patients with CKD.
• ACEI/ARB Combination Therapy: A 2021 meta-analysis 5 demonstrated that ACEI in combination with ARB was superior to low-dose ACEI or ARB in reducing urine albumin excretion, urine protein excretion, and blood pressure in patients with CKD.
• ACE Inhibitor/Calcium Antagonist Combination Therapy: A 2018 study 6 compared the long-term effect of two ACE inhibitor/calcium antagonist combinations on renal function in hypertensive patients with CKD and found that combined therapy with an ACE inhibitor and T/L type calcium antagonist may prevent deterioration of renal function more effectively than an ACE inhibitor/L type calcium antagonist combination in patients with diabetic nephropathy.
• Management of Heart Failure in CKD: A 2021 review 7 discussed the management of heart failure in patients with CKD and highlighted the benefits of renin-angiotensin-aldosterone axis inhibitor therapy, including ACEIs and ARBs, in patients with mild-to-moderate CKD.
• Predicting Hyperkalemia Risk: A 2010 study 8 developed a prognostic risk score to predict the risk of hyperkalemia in patients with CKD starting ACEIs, which can help identify high-risk patients who may require more intensive laboratory monitoring.

Key Findings

• ACEIs and ARBs are effective in reducing proteinuria and preventing structural lesions in CKD patients.
• Combination therapy with ACEIs and ARBs may be more effective than monotherapy in reducing urine albumin excretion, urine protein excretion, and blood pressure.
• ACE inhibitor/calcium antagonist combination therapy may be beneficial in preventing deterioration of renal function in patients with diabetic nephropathy.
• Renin-angiotensin-aldosterone axis inhibitor therapy, including ACEIs and ARBs, can be beneficial in patients with mild-to-moderate CKD.
• Predicting hyperkalemia risk is crucial in patients with CKD starting ACEIs to ensure safe and effective management.