From the Guidelines
Stage 4 chronic kidney disease (CKD) is generally considered a contraindication to using mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone, as the estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73m² significantly increases the risk of hyperkalemia, which can be life-threatening. According to the 2022 AHA/ACC/HFSA guideline for the management of heart failure, MRAs are recommended to reduce morbidity and mortality in patients with HFrEF and NYHA class II to IV symptoms, but only if the eGFR is >30 mL/min/1.73 m2 and serum potassium is <5.0 mEq/L 1.
The kidneys play a crucial role in potassium excretion, and in advanced CKD, this function is severely compromised. MRAs block aldosterone receptors, which further reduces potassium excretion, creating a "perfect storm" for dangerous potassium elevation. The expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors also recommends avoiding MRAs if serum potassium levels are >5.0 mEq/L 1.
If treatment with an MRA is absolutely necessary in a patient with stage 4 CKD, it should only be done under very close supervision with frequent monitoring of serum potassium and kidney function (at least weekly initially), starting at the lowest possible dose (such as spironolactone 12.5 mg daily or even every other day). Additionally, patients should be counseled about avoiding high-potassium foods and other medications that can raise potassium levels, such as NSAIDs, ACE inhibitors, and ARBs when possible. Key considerations include:
- Frequent monitoring of serum potassium and kidney function
- Starting at the lowest possible dose
- Counseling patients on avoiding high-potassium foods and medications
- Close supervision to minimize the risk of hyperkalemia and renal insufficiency.
From the FDA Drug Label
For all patients: • Serum potassium >5.5 mEq/L at initiation ( 4) • Creatinine clearance ≤30 mL/min ( 4) For the treatment of hypertension: • Type 2 diabetes with microalbuminuria ( 4) • Serum creatinine >2.0 mg/dL in males, >1.8 mg/dL in females ( 4) • Creatinine clearance <50 mL/min ( 4)
Stage 4 CKD is defined as a creatinine clearance of 15-29 mL/min. The provided drug label for eplerenone 2 states that a creatinine clearance ≤30 mL/min is a contraindication. Therefore, stage 4 CKD is a contraindication to using eplerenone, a type of MRA.
From the Research
Stage 4 CKD and MRAs
- Stage 4 CKD is a condition where the kidneys are severely damaged and are not able to filter waste and excess fluids effectively 3, 4, 5.
- Mineralocorticoid receptor antagonists (MRAs) are a type of medication that can help to reduce blood pressure and protect the kidneys, but they can also increase the risk of hyperkalemia (high potassium levels) 6, 7.
- The use of MRAs in patients with stage 4 CKD is not absolutely contraindicated, but it requires careful consideration and monitoring of potassium levels 4, 6.
- Some studies have shown that MRAs can be effective in reducing blood pressure and protecting the kidneys in patients with stage 4 CKD, but they also increase the risk of hyperkalemia 4, 7.
Hyperkalemia Risk
- Hyperkalemia is a serious condition that can occur in patients with stage 4 CKD, especially when they are taking MRAs or other medications that can increase potassium levels 3, 5.
- The risk of hyperkalemia can be mitigated by monitoring potassium levels regularly and adjusting the dose of MRAs or other medications as needed 4, 6.
- Potassium binders, such as patiromer and sodium zirconium cyclosilicate, can also be used to help reduce potassium levels in patients with hyperkalemia 3, 5.
Clinical Considerations
- The decision to use MRAs in patients with stage 4 CKD should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 4, 7.
- Patients with stage 4 CKD who are taking MRAs should be closely monitored for signs of hyperkalemia, such as muscle weakness, palpitations, and shortness of breath 3, 5.
- The use of MRAs in combination with other medications, such as ACE inhibitors or ARBs, may increase the risk of hyperkalemia and requires careful consideration and monitoring 7.