What is the most appropriate pharmacological management for a patient with hyperkalemia (elevated potassium levels) and impaired renal function, who is currently taking Lisinopril (Zestril) (angiotensin-converting enzyme inhibitor)?

From the Guidelines

A patient with heart failure and reduced ejection fraction (HFrEF) should be treated with renin-angiotensin-aldosterone system inhibitors (RAASi) as the cornerstone of treatment, despite the risk of hyperkalemia, as the benefits of reduced mortality and morbidity outweigh the risks 1. When managing hyperkalemia in patients with cardiovascular disease treated with RAASi, it is essential to consider the potential causes of hyperkalemia, including decreased potassium excretion and increased potassium intake.

• Decreased potassium excretion can be caused by various factors, such as:
  • Potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride)
  • Beta-blockers
  • NSAIDs
  • Sacubitril/valsartan
  • Renin-angiotensin-aldosterone inhibitors (RAASi): ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists (MRAs)
  • Direct renin inhibitors (aliskiren)
• Increased potassium intake can be caused by:
  • Potassium supplements
  • Salt substitute (e.g., DASH)
  • Fruits (bananas, melons, orange juice)
  • Alfalfa
  • Amino acids (aminocaproic acid, arginine, lysine) According to 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, RAASi are recommended as the first-line treatment for patients with HFrEF, with a Class IA recommendation 1. The use of RAASi should be individualized, and patients should be monitored closely for signs of hyperkalemia, with prompt treatment initiated if necessary, using a combination of calcium carbonate, hyperosmolar sodium, insulin, and beta-adrenoceptor agonists, as well as potassium-lowering agents such as loop diuretics and potassium binders 1.

From the FDA Drug Label

Anaphylactoid Reactions During Dialysis Sudden and potentially life threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor.

1. 3 Impaired Renal Function Monitor renal function periodically in patients treated with lisinopril.

2. 4 Hypotension Lisinopril can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure or death

3. 4 Dose in Patients with Renal Impairment No dose adjustment of lisinopril tablets is required in patients with creatinine clearance > 30 mL/min.

Difficult Pharmacology Question for the Boards:

• What are the potential risks and considerations when administering lisinopril to a patient with renal impairment and hypertension, and how should the dose be adjusted in this scenario, considering the patient is also undergoing dialysis? 2 2

From the Research

Difficult Pharmacology Question for the Boards

• What is the most appropriate pharmacological approach for a patient with concomitant heart failure, chronic kidney disease, and diabetes mellitus, considering the potential benefits and risks of various medications, including spironolactone, metformin, and sodium-glucose co-transporter-2 inhibitors, as discussed in studies 3, 4, 5, 6, 7?

Key Considerations

• The use of spironolactone in patients with heart failure and chronic kidney disease may be beneficial, but requires careful monitoring due to the risk of hyperkalemia and reduction in glomerular filtration rate, as noted in 3.
• Metformin may be associated with reduced all-cause mortality in patients with chronic kidney disease, congestive heart failure, or chronic liver disease, but its use requires careful consideration of renal function and potential contraindications, as discussed in 6.
• Sodium-glucose co-transporter-2 inhibitors and non-steroidal mineralocorticoid receptor antagonists may offer cardiorenal protection in patients with diabetes and heart failure, but their use should be guided by current clinical evidence and recommendations, as outlined in 7.
• The management of heart failure, chronic kidney disease, and diabetes mellitus requires a comprehensive approach that takes into account the complex interplay between these conditions and the potential benefits and risks of various medications, as highlighted in 4, 5.