What are the considerations for using amlodipine (Calcium Channel Blocker) in a patient with Chronic Kidney Disease (CKD) and fluid retention who is not responding to diuretics (loop diuretics)?

From the Guidelines

Amlodipine can be a beneficial addition for CKD patients with fluid retention who aren't responding adequately to loop diuretics, as recommended in the KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease 1. The typical starting dose is 2.5-5 mg once daily, which can be titrated up to 10 mg daily if needed and tolerated. Amlodipine works well in CKD because it maintains efficacy even with reduced kidney function and doesn't require dose adjustment in renal impairment. When adding amlodipine to a diuretic regimen, monitor for potential side effects including peripheral edema (which may paradoxically worsen fluid retention symptoms), hypotension (especially with concurrent diuretics), and potential drug interactions with immunosuppressants like cyclosporine or tacrolimus in transplant recipients. The medication's effectiveness stems from its ability to reduce peripheral vascular resistance and afterload through arterial vasodilation, which can improve cardiac output and potentially enhance diuretic response. Additionally, amlodipine offers renoprotective effects by reducing intraglomerular pressure and proteinuria, making it particularly valuable in the CKD population. Blood pressure should be monitored closely during initiation and dose adjustments, with particular attention to orthostatic changes when combined with diuretics.

Some key considerations when using amlodipine in CKD patients with fluid retention include:

• Monitoring for signs of fluid overload, such as edema and shortness of breath
• Adjusting the dose of amlodipine based on blood pressure response and tolerance
• Considering the use of other antihypertensive agents, such as ACE inhibitors or ARBs, in combination with amlodipine
• Being aware of potential drug interactions, such as those with immunosuppressants or other antihypertensive agents.

It's also important to note that the use of diuretics in CKD patients with fluid retention is a key element in the management of these patients, as recommended in the 2013 ACCF/AHA guideline for the management of heart failure 1. However, the addition of amlodipine can be beneficial in patients who are not responding adequately to loop diuretics, as it can help to reduce blood pressure and improve cardiac output.

In terms of specific guidance, the KDIGO 2021 clinical practice guideline recommends starting with a 2- or 3-drug therapy using a combination of a thiazide-type diuretic, and/or an ACEI or ARB (but not both) and/or a CCB, such as amlodipine 1. The guideline also recommends monitoring blood pressure closely and adjusting therapy as needed to achieve a target systolic blood pressure of less than 120 mmHg.

Overall, the use of amlodipine in CKD patients with fluid retention who are not responding to loop diuretics can be a valuable addition to the treatment regimen, as long as it is used carefully and with close monitoring of blood pressure and potential side effects.

From the FDA Drug Label

Amlodipine besylate tablets may be used alone or in combination with other antihypertensive agents. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease).

The use of Amlodipine in a patient with Chronic Kidney Disease (CKD) and fluid retention who is not responding to diuretics should be considered with caution.

• Key considerations:
  • Amlodipine can be used in combination with other antihypertensive agents.
  • Its effects on blood pressure may vary in different patient populations.
  • There is no direct information in the label about its use in patients with CKD and fluid retention who are not responding to diuretics.
  • The label does mention that some antihypertensive drugs have effects on diabetic kidney disease, but this is not directly relevant to the question.
  • Amlodipine may be used to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure in patients with angiographically documented CAD. However, the label does not provide direct guidance on using Amlodipine in patients with CKD and fluid retention who are not responding to diuretics 2.

From the Research

Considerations for Using Amlodipine in CKD Patients with Fluid Retention

• The use of amlodipine, a calcium channel blocker, in patients with Chronic Kidney Disease (CKD) and fluid retention who are not responding to diuretics requires careful consideration of the patient's overall clinical condition 3.
• CKD patients often experience sodium retention, leading to increased plasma volume and blood pressure, which can be exacerbated by the renin-angiotensin-aldosterone system 3.
• Diuretics, such as loop diuretics, are commonly used to manage volume overload in CKD patients, but may not be effective in all cases 3.
• Mineralocorticoid receptor antagonists (MRAs) have been shown to be effective in reducing proteinuria and improving cardiovascular outcomes in CKD patients, and may be considered as an alternative or adjunct to diuretics 4, 5, 6.
• The use of MRAs in CKD patients has been associated with a reduction in albuminuria and proteinuria, as well as a slight increase in mean potassium levels 6.
• Amlodipine may be considered as a treatment option for hypertension in CKD patients, but its use in patients with fluid retention and diuretic resistance requires careful monitoring of renal function and electrolyte levels 3.

Potential Benefits and Risks of Amlodipine in CKD Patients

• Potential benefits of amlodipine in CKD patients include:
  • Reduction in blood pressure
  • Improvement in cardiovascular outcomes
• Potential risks of amlodipine in CKD patients include:
  • Worsening of renal function
  • Hyperkalemia
  • Edema

Monitoring and Management of CKD Patients on Amlodipine

• Close monitoring of renal function, electrolyte levels, and blood pressure is essential in CKD patients treated with amlodipine 3, 7.
• Adjustment of diuretic therapy and consideration of alternative treatments, such as MRAs, may be necessary in patients with diuretic resistance or worsening renal function 4, 5, 6.
• Education on dietary sodium restriction and fluid management is crucial in CKD patients with fluid retention 3.