What is a suitable second antihypertensive medication for a patient with impaired renal function (Chronic Kidney Disease, CKD) who is already taking maximum doses of amlodipine (Calcium Channel Blocker)?

From the Guidelines

For a patient with chronic kidney disease (CKD) who is already on maximum-dose amlodipine, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) would be the recommended second-line medication, as supported by the most recent guideline evidence 1. Specific options include lisinopril (10-40 mg daily), ramipril (2.5-10 mg daily), or losartan (25-100 mg daily), with dosing adjusted based on kidney function. These medications are particularly beneficial in CKD patients as they not only lower blood pressure but also reduce proteinuria and slow CKD progression, as noted in studies such as the FIDELIO trial 1. When initiating these medications, monitor serum creatinine and potassium levels within 1-2 weeks, as they can cause acute increases in creatinine and hyperkalemia, especially in advanced CKD, as advised in the 2020 KDIGO clinical practice guideline 1. Start with a lower dose and titrate up gradually. If the patient has significant proteinuria, prioritize ACE inhibitors or ARBs even more strongly. For patients who cannot tolerate these medications due to hyperkalemia or significant reduction in GFR, alternatives include thiazide diuretics (for mild-moderate CKD) or loop diuretics (for advanced CKD), with careful attention to electrolyte balance, as suggested by various guidelines including the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.

Some key points to consider when managing hypertension in patients with CKD include:

• The importance of using ACE inhibitors or ARBs as first-line therapy, unless contraindicated, due to their renoprotective effects 1.
• The need for careful monitoring of serum creatinine and potassium levels when initiating or adjusting ACE inhibitors or ARBs, especially in patients with advanced CKD 1.
• The consideration of alternative antihypertensive agents, such as thiazide or loop diuretics, in patients who cannot tolerate ACE inhibitors or ARBs due to hyperkalemia or significant reduction in GFR 1.

Overall, the management of hypertension in patients with CKD requires a thoughtful and individualized approach, taking into account the patient's specific clinical characteristics, comorbidities, and potential contraindications to certain medications.

From the FDA Drug Label

Use with diuretics in adults If blood pressure is not controlled with lisinopril tablets alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12. 5 mg). 2. 4 Dose in Patients with Renal Impairment No dose adjustment of lisinopril tablets is required in patients with creatinine clearance > 30 mL/min. In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of lisinopril tablets to half of the usual recommended dose i.e., hypertension, 5 mg; systolic heart failure, 2.5 mg and acute MI, 2. 5 mg.

For a patient maxed out on amlodipine with CKD, a good second medication could be lisinopril, considering the patient's renal function.

• The dose of lisinopril should be adjusted based on the patient's creatinine clearance.
• If the patient has a creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, the initial dose of lisinopril should be reduced to half of the usual recommended dose, which is 2.5 mg for hypertension.
• The patient should be closely monitored for any signs of hypotension or worsening renal function. 2

From the Research

Treatment Options for Patients with CKD

For a patient maxed out on amlodipine with chronic kidney disease (CKD), several treatment options can be considered as a second medication:

• Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) can be effective in reducing urine albumin excretion and urine protein excretion, as shown in a systematic review and meta-analysis 3.
• Losartan, an ARB, has been shown to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with its mechanism being independent of its antihypertensive action 4.
• Calcium antagonists, such as amlodipine, can be added to renin-angiotensin system inhibitors to treat hypertension with CKD, and have been shown to exert a greater decrease in urinary protein excretion than diuretics when blood pressure is similarly controlled 5.
• Fixed-dose combinations of S-amlodipine and telmisartan have been shown to be effective and safe in patients with hypertension inadequately controlled with S-amlodipine monotherapy, with superior blood pressure-lowering effects compared to S-amlodipine monotherapy 6.

Considerations for CKD Patients

When selecting a second medication for a patient with CKD, it is essential to consider the potential risks and benefits, including:

• The risk of decreased glomerular filtration rate (GFR) and increased rates of hyperkalemia and hypotension associated with ACEIs and ARBs 3.
• The potential for calcium antagonists to improve augmentation index and reduce urinary protein excretion 5.
• The importance of monitoring blood pressure, renal function, and electrolyte levels in patients with CKD 7.