What alternative medication can be used to manage hypertension in a patient with AKI, taking lisinopril and chlorthalidone, and previously on Amlodipine?

From the Guidelines

For a patient with acute kidney injury (AKI) who is currently taking lisinopril and chlorthalidone, and previously took amlodipine, I recommend temporarily discontinuing both lisinopril and chlorthalidone and switching to a calcium channel blocker such as amlodipine (5-10 mg daily) or a beta-blocker like metoprolol (25-100 mg twice daily). ACE inhibitors like lisinopril can worsen kidney function in AKI by reducing glomerular filtration pressure, while diuretics like chlorthalidone can exacerbate volume depletion and further compromise renal perfusion, as noted in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. Calcium channel blockers are generally safer in AKI as they don't directly affect kidney hemodynamics and can effectively control blood pressure without worsening kidney function. If the patient previously tolerated amlodipine well, restarting it would be a reasonable first choice, considering the dose range of 2.5-10 mg daily as suggested in the guideline 1. Beta-blockers like metoprolol are also relatively safe in AKI, with a recommended dose range of 25-100 mg twice daily 1. Blood pressure and kidney function should be closely monitored, with laboratory tests checking creatinine and electrolytes every 2-3 days initially. Once the AKI resolves, the original antihypertensive regimen can be cautiously reintroduced if appropriate, starting with low doses and gradually titrating up while monitoring kidney function. Key considerations include:

• Monitoring for signs of worsening kidney function or hyperkalemia, especially when using ACE inhibitors or ARBs, as cautioned in the guideline 1.
• Avoiding the use of potassium-sparing diuretics in patients with significant CKD (eGFR <45 mL/min), as advised in the guideline 1.
• Considering alternative antihypertensive agents, such as alpha-1 blockers or central alpha2-agonists, if necessary, while being mindful of their potential side effects and interactions, as discussed in the guideline 1.

From the FDA Drug Label

Peripheral Edema— Peripheral edema, generally mild and not associated with generalized fluid retention, was the most common adverse event in the clinical trials. The incidence of peripheral edema was both dose and age dependent. Frequency of peripheral edema ranged from about 10% in patients under 50 years of age taking 5 mg daily to about 30% in those over 60 years of age taking 20 mg daily

The patient is 66 years old and has a history of pedal edema, which led to the discontinuation of Amlodipine. Considering the patient's age and history, felodipine may not be the best alternative due to the high incidence of peripheral edema in patients over 60 years old.

• The patient's renal function is also a concern, with a BUN of 32, creatinine of 1.82, and eGFR of 40, indicating acute kidney injury (AKI).
• There is no direct information in the provided drug label that supports the use of felodipine in patients with AKI or provides guidance on dosage adjustments in this population 2. The FDA drug label does not answer the question.

From the Research

Alternative Medications for Hypertension in AKI

Given the patient's current medication regimen of lisinopril and chlorthalidone, and the discontinuation of Amlodipine due to pedal edema, alternative medications for managing hypertension in the context of Acute Kidney Injury (AKI) need to be considered. The patient's renal function, indicated by a BUN of 32, creatinine of 1.82, and eGFR of 40, suggests a need for careful selection of antihypertensive agents that are safe and effective in the setting of impaired renal function.

Considerations for Medication Selection

• Renal Protection: Medications that offer renal protection, such as angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs), are beneficial in patients with kidney disease. However, the patient is already on lisinopril, an ACE inhibitor.
• Blood Pressure Control: Effective blood pressure control is crucial to prevent further kidney damage. The choice of medication should be based on its ability to control blood pressure without adversely affecting renal function.
• Side Effects: The medication should have a favorable side effect profile, especially considering the patient's previous experience with pedal edema on Amlodipine.

Potential Alternative Medications

• Beta-Blockers: Could be considered as an alternative or addition to the current regimen, especially if there are concerns about heart rate or cardiac function. However, their effectiveness in slowing the progression of kidney disease is less clear compared to ACE inhibitors or ARBs 3.
• Calcium Channel Blockers: While Amlodipine was discontinued due to side effects, other calcium channel blockers might be considered, keeping in mind their potential benefits and risks in patients with AKI. Amlodipine has been shown to be effective in reducing blood pressure in various patient populations, including those with hypertension 4.
• Diuretics: The patient is already on chlorthalidone, a diuretic. Adjusting the dose or switching to another type of diuretic might be necessary based on the patient's response and renal function.

Evidence and Justification

The decision to use any of these alternatives should be guided by evidence and individual patient factors. For instance, the study by 3 suggests that ACE inhibitors may be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing the decline in glomerular filtration rate (GFR) in patients with hypertensive kidney disease. However, this patient is already on an ACE inhibitor, so the focus might be on adding a medication from a different class.

Given the complexity of managing hypertension in the context of AKI and the need to balance blood pressure control with renal protection, careful consideration of the patient's overall clinical picture is necessary. The patient's response to current medications, potential side effects, and the need to avoid further kidney damage should guide the selection of any additional or alternative antihypertensive medications.