What is the treatment for primary hyperaldosteronism in patients with Chronic Kidney Disease (CKD)

From the Guidelines

For patients with primary hyperaldosteronism and chronic kidney disease (CKD), the recommended treatment approach is to use mineralocorticoid receptor antagonists (MRAs), with careful dose adjustment and monitoring, as stated in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. The treatment should start with spironolactone at a low dose of 25 mg daily, titrating up to a maximum of 100 mg daily as tolerated. If spironolactone is not well-tolerated, consider eplerenone as an alternative, starting at 25 mg daily and increasing to 50 mg twice daily if needed. It's crucial to monitor serum potassium and renal function closely, initially weekly then monthly once stable. If hyperkalemia occurs, reduce the dose or consider adding a potassium-binding agent. In patients with more advanced CKD (stages 4-5), start with even lower doses and titrate more cautiously. For patients who cannot tolerate MRAs or have uncontrolled hypertension, adding an ACE inhibitor or angiotensin receptor blocker (ARB) may be beneficial, as suggested by the 2017 ACC/AHA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. These drugs can help manage blood pressure and protect kidney function, but require careful monitoring due to the risk of further reducing GFR. In cases where a unilateral aldosterone-producing adenoma is identified and the patient is a suitable surgical candidate, adrenalectomy should be considered as it can potentially cure the condition, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. The rationale for using MRAs is their direct antagonism of aldosterone's effects, reducing sodium retention and potassium excretion, which helps control blood pressure and mitigates the harmful effects of excess aldosterone on the cardiovascular and renal systems, as discussed in the guideline-driven management of hypertension: an evidence-based update 1. The cautious approach in CKD patients is necessary due to their reduced ability to excrete potassium and increased susceptibility to further renal function decline. Some key points to consider when treating primary hyperaldosteronism in patients with CKD include:

• Monitoring serum potassium and renal function closely
• Starting with low doses of MRAs and titrating cautiously
• Considering alternative treatments, such as ACE inhibitors or ARBs, if MRAs are not tolerated or effective
• Evaluating the patient for surgical candidacy if a unilateral aldosterone-producing adenoma is identified.

From the FDA Drug Label

2.5 Treatment of Primary Hyperaldosteronism Administer spironolactone in doses of 100 mg to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone can be used as long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

The treatment for primary hyperaldosteronism is spironolactone administered in doses of 100 mg to 400 mg daily. However, the provided drug labels do not specifically address the treatment of primary hyperaldosteronism in patients with Chronic Kidney Disease (CKD).

• In patients with an eGFR between 30 and 50 mL/min/1.73 m^2, the drug label suggests considering initiating therapy at 25 mg every other day because of the risk of hyperkalemia 2. However, this information is not directly related to the treatment of primary hyperaldosteronism in patients with CKD. Therefore, a conservative clinical decision would be to exercise caution when using spironolactone in patients with CKD and primary hyperaldosteronism, and consider consulting additional resources or guidelines for specific advice on treatment in this population.

From the Research

Treatment Options for Primary Hyperaldosteronism in Patients with CKD

• The treatment of primary hyperaldosteronism in patients with Chronic Kidney Disease (CKD) can be challenging due to the complexity of the disease and the potential risks associated with certain treatments 3, 4.
• Medical treatment with mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, is often considered the first line of treatment for patients with bilateral adrenal hyperplasia or those who are not surgical candidates 5, 6.
• Adrenalectomy, either unilateral or bilateral, may be considered for patients with lateralized primary aldosteronism, but the decision to operate should be made on a case-by-case basis, taking into account the patient's overall health, kidney function, and potential risks associated with surgery 7, 4.
• The optimal strategy for the diagnosis and management of primary aldosteronism in patients with CKD is not well established, and further studies are needed to determine the best approach 3, 4.

Considerations for Patients with CKD

• Patients with CKD may require closer monitoring of serum electrolyte and creatinine levels when starting medical treatment for primary hyperaldosteronism 5.
• The use of potassium-sparing diuretics, such as amiloride or triamterene, may be necessary in addition to mineralocorticoid receptor antagonists to control blood pressure and potassium levels 5.
• Adrenalectomy may be associated with improved blood pressure control and reduced medication burden in patients with CKD, but the decision to operate should be made on a case-by-case basis 4.

Novel Therapies and Future Directions

• Novel therapies, such as nonsteroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, are being developed as alternative options for the treatment of primary hyperaldosteronism 6.
• Further studies are needed to determine the efficacy and safety of these novel therapies in patients with CKD and primary hyperaldosteronism 3, 4.